September/October 2015

Bridging the gap between the hospital and alternate-site care Volume 4 • Number 4 • September/October 2015 • specialtypharmacycontinuum.com

‘Real people can’t afford these drugs’

Clinical NEW FEATURE

3 4 10 12

Copay Assistance: A Key To Survival of Specialty?

FAQ: Customized IG product selection.

Oral chemotherapy and safe handling: managing the risks.

Rapid growth, new drugs eyed for hemophilia.

A specialty pharmacy approach to managing multiple sclerosis.

Operations & Mgmt

17 18

Why accreditation matters.

New hepatitis C drugs bring new players into specialty pharmacy.

The Internet of Things: linking caregivers to patients.

Disease State Spotlight

PCSK9 Inhibitors: A New Treatment Paradigm for Severe Hyperlipidemia See page 6

T

he 340B mega-guidance recently proposed by the Health Resources and Services Administration (HRSA) will greatly affect specialty and hospital pharmacists, narrowing the scope of a qualified patient, which drugs can be purchased through 340B pricing, and better defining the relationship between eligible facility and outpatient centers and the services they must perform.

The 340B Drug Pricing Program, which was started in 1992 to enable safety-net health care providers to purchase medications at lower pricing to provide better care for underserved populations, has been described as one see 340B MEGA-RULE, page 20

Biosimsimilars: Still Causing Support, Concern

Technology

22

340B Mega-Rule Yields Clarity— And Controversy

Las Vegas—In a recent meeting with pharmaceutical manufacturers about copay coupons and other forms of patient assistance, Daniel Kus, BSPharm, RPh, the vice president of ambulatory pharmacy services for Henry Ford Health System in Detroit, presented some dramatic numbers underscoring the importance of these programs to his specialty pharmacy patients.

“The average patient who has a prescription filled at Pharmacy Advantage, our specialty pharmacy, has an annual copay of about $1,550 for a single specialty medication,” Mr. Kus said. “That’s an average across the payor mix with all insurances. After we do copay cards and other financial assistance, the average copay drops to $2.48.”

Nearly eight of 10 patients at Henry Ford’s specialty pharmacy receive some form of copay assistance, Mr. Kus said. That’s hardly surprising, given the state of specialty pharmacy costs and current copay/deductible practices. “Most individuals in our marketplace have anywhere from $2,000 to $10,000 in up-front deductibles, and I think every specialty pharmacy is experiencing what we are.”

He’s right, said Zitter Health Insights’ founder and CEO Mark Zitter, in a session on copay assistance at the 2015 Armada Specialty Pharmacy Summit. “Cost sharing

wo separate arms of the federal government have issued somewhat competing proposed regulations on the naming, coding and reimbursement of biosimilars, stirring both support and censure.

A rule proposed by the Centers for Medicare & Medicaid Services (CMS) recommends using one reimbursement code for all biosimilars of the same reference product, whereas a separate FDA draft guidance indicates the agency will require clinicians to identify and prescribe biosimilars by name.

Comments from various stakeholders indicate that the two rules are in conflict

see COPAY HELP, page 16

see BIOSIMILARS, page 21

T

Now Available Specialty Pharmacy Sp Continuum iPad App

FDA Approval Two new PCSK9 inhibitors approved for lipid lowering.

See page 7

CAREGIVER. PATIENT. SURVIVOR.

OUR SPECIALTY PHARMACY RESOURCES + A CARING TOUCH Brenda cared for her husband during his battle with cancer. She was there—offering support, going to every appointment and making sure he took his prescription on time. Later, when she was diagnosed with breast cancer, the caregiver became the patient. Her husband was there every step of the way, and so was her pharmacy team.

Personal experiences like those would later inspire her to become a patient advocate with Diplomat.

Diplomat is a different kind of specialty pharmacy. The patient is at the center of everything we do. We strive to give the high-touch care you would expect for someone you love. Our care team includes pharmacists that are some of the best in the Þeld. We are Diplomat, and we are here to serve.

SEE BRENDA’S STORY AND LEARN MORE ABOUT OUR EFFORTS AT DIPLOMAT.IS/HERE HELP US CELEBRATE NATIONAL PHARMACY WEEK WITH #WEAREHERE @DIPLOMATRX

Copyright © 2015 by Diplomat Pharmacy Inc. Diplomat is a registered trademark of Diplomat Pharmacy Inc. All rights reserved.

MARK-002614-0915

BRENDA BREAST CANCER SURVIVOR DIPLOMAT, MANAGER OF PATIENT ADVOCACY

DIPLOMAT CELEBRATES BREAST CANCER AWARENESS MONTH

3

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

FAQ: Customized IG Product Selection Q: When is a different immune globulin (IG) product warranted, and how should the selection be made?

A: Matching the best IG product to the patient is often not just a one-time event, because the patient’s comorbidities and tolerances change over time. The following simulated case demonstrates the full range of this type of product selection and transition. Use of the educational review, “Immune Globulins: Therapeutic, Pharmaceutical, Cost, and Administration Considerations” as a guide for product selections ((Pharmacy Practice News 2015;42[1]:13-19) will be helpful to understand how to navigate these choices.

patient develops type 2 diabetes and shows signs of renal insufficiency with elevated blood urea nitrogen and serum creatinine levels. The physician has decided to change to a liquid IVIG formulation that does not contain sucrose, but is also concerned about the volume of fluid, partly because the patient’s weight has increased to 100 kg. Should the dose be based on the patient’s actual weight, adjusted weight, or lean body weight?

In this patient with primary immune deficiency, an immunoglobulin G level could be measured to determine when the level drops below 600 mg/ dL, as well as to see whether a dose below actual body weight is justified.

At this point, the physician chooses a 10% liquid product with a glycine stabilizer at a dose of 500 mg/kg.

With this 10% IG product, the dose is 50 g or 500 mL. The patient tolerates this product well with no headache or other side effects following an infusion time of 2 hours, including dose escalation. She is happy with this change because of the decreased infusion time, and she is no longer experiencing headaches. The patient remains on this product for 3 more years, but during this time has developed an episode of aseptic meningitis 5 days after the last infusion. This adverse event came as a total surprise, but no other explanation could be ruled out. The patient’s renal status is now worse, with a renal function creatinine Case Report clearance of less than 30 mL/min. The A 50-year-old morbidly obese female physician now has to decide whether patient with primary immune defihe should change the dose, the prodciency is treated with a 6% uct, or the rate of infusion. The Immunoglobulin G (IgG) lyophilized IG product. The physician decides to do all of the maintenance dose is 500 above and changes to a different mg/kg every 4 weeks. The patient 10% IG product that is formulatweighs 90 kg and her body mass ed with a proline stabilizer. The index is 34 kg/m2. The dose is physician reduces the dose to 400 mg/kg and slows the infubased on actual weight and thus is 45 g (750 mL). The usual infusion rate to a maximum infusion rate of 4 mg/kg per minute with sion time, including escalation, is Foreign particle Foreign particle binding site binding site a slow escalation.

5.5 hours, with mild headache as a common side effect. The patient The patient tolerates the infudoes not take any premedications. sion but develops a severe headOver the next few years, the ache during the infusion, so it is

Jerry Siegel, PharmD, FASHP Senior Director of Pharmaceutical Services The Ohio State University Medical Center Columbus, Ohio

slowed to 2 mg/kg per minute, which results in a total infusion time of 6 hours. The patient did not experience aseptic meningitis but was not satisfied with the duration of infusion and the severity of the headache. Before the next infusion, the patient was given 650 mg of acetaminophen and 50 mg of diphenhydramine. The headache was not as severe, but the antihistamine made the patient so drowsy that a caregiver had to be called for a ride home, and the patient was not able to work the following day.

After several more similar infusion experiences, the patient asked for alternative IG treatment options. The physician, seeking more information upon which to base any therapeutic switches, discussed subcutaneous options with the pharmacist. There are three 10% IG products that can be given not only intravenously but also see IG SELECTION, page 5

EDITORIAL BOARD

ART/PRODUCTION STAFF

HOME INFUSION

Michele McMahon Velle, MAX Graphics/Creative Director

Jay Bryant-Wimp, RPh Owner/CEO Accurate Rx Pharmacy Columbia, MO

Frank Tagarello, Senior Art Director/Managing / Director, r MAX Graphics James O’Neill, Senior Systems Manager

Randy Fasnacht, RPh Director of Pharmacy Advanced Infusion Services Akron, OH

Dan Radebaugh, Director of Production and Technical Operations

Volume 4 • Number 4 • September/October 2015

specialtypharmacycontinuum.com

Marty Barbieri, Production Manager Brandy Wilson, Circulation Manager

SPECIALTY PHARMACY N. Lois Adams, MBA, RPh Chairman, President and CEO Freedom Pharmacy Orlando, FL Randy Falkenrath, MBA Senior Vice President CVS Health Woonsocket, RI

McMAHON PUBLISHING Michael Sicilian President, Managed Health Care Associates Inc. Florham Park, NJ Donald J. Vidic, RPh, MBA Vice President of Operations and Pharmacy Services Walgreens Specialty Pharmacy Carnegie, PA

Stephanie Holliday, PharmD Clinical Pharmacy Specialist Prosperity Specialty Pharmacy Falls Church, VA Cindy Kunzendorf, PharmD General Manager Accredo/CCS Locations Elmhurst, IL Hetty Lima, RPh, FASHP Vice President of Specialty Infusion Services Diplomat Specialty Pharmacy Flint, MI

CHANGE YOUR ADDRESS? HERE’S HOW Selected U.S. hospital pharmacists and health care personnel receive Specialty Pharmacy Continuum free of charge. If you are a hospital pharmacist and do not receive the publication, you must add your professional address

A family-owned medical publishing and medical education company. McMahon publishes seven clinical newspapers and several annual or semiannual Special Editions.

Marie Rosenthal, Senior Editor mrosenthal@mcmahonmed.com Kevin Horty, Don Pizzi, Adam Marcus, Contributing Editors James Prudden, Group Editorial Director Elizabeth Zhong, Senior Copy Editor Kristin Jannacone, Copy Editor

HEALTH-SYSTEM PHARMACY Ernest R. Anderson Jr., MS, RPh Brockton, MA

REIMBURSEMENT Bonnie Kirschenbaum, MS Breckenridge, CO

EDITORIAL STAFF

SALES David Kaplan, Group Publication Director dkaplan@mcmahonmed.com Matt Spoto, Senior Account Manager mspoto@mcmahonmed.com Lillie Onday, Account Manager londay@mcmahonmed.com

David Bronstein, Editorial Director davidb@mcmahonmed.com

Craig Wilson, Sales Associate, Classified Advertising cwilson@mcmahonmed.com

or make your address change directly with Specialty Pharmacy Continuum, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036. You can also fax your request to (212) 977-3645, or send it via email, circulation@ mcmahonmed.com. If you are not a hospital pharmacist but would like to receive Specialty Pharmacy Continuum, please send a check for $70.00 (U.S.) or $90.00 (outside

U.S.) for a year’s subscription payable to Specialty Pharmacy Continuum to McMahon Publishing, 545 West 45th St., 8th Floor, New York, NY 10036. Please allow 8 to 12 weeks for delivery of the first issue. Individual issues are $7.00 (U.S.) or $10.00 (outside U.S.).

McMahon Publishing is a 43-year-old, first-generation, family-owned publishing company dedicated to providing

Raymond E. McMahon, Publisher and Managing Partner Van Velle, President, Partner Matthew McMahon, General Manager, Partner Lauren McMahon Smith, Michael McMahon, Michele McMahon Velle, Rosanne C. McMahon, Partners

MCMAHON PUBLISHING MCMAHONMED.COM Sales, Production and Editorial Offices: 545 West 45th Street, 8th Floor, New York, NY 10036 Telephone: (212) 957-5300 Copyright © 2015 McMahon Publishing, New York, NY 10036. All rights reserved. Specialty Pharmacy Continuum (ISSN 0886-988x) is published quarterly by McMahon Publishing. Periodicals postage paid at New York, NY, and at additional mailing offices. POSTMASTER: Send address changes to Specialty Pharmacy Continuum, Circulation Dept., 545 W. 45th St., 8th Floor, New York, NY 10036.

medical professionals with essential, up-to-date news. As the second largest publisher of medical newspapers, McMahon produces Anesthesiology News, Clinical Oncology News, Gastroenterology & Endoscopy News, General Surgery News, Infectious Disease Special Edition, Pain Medicine News and Pharmacy Practice News.

4

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

Oral chemotherapy:

Boosting Safety for Patients, Family, Providers More than 30 oral anticancer drugs have been approved by the FDA over the past 10 years alone, and it’s estimated that oral agents comprise more than 30% of the approximately 900 chemotherapy treatments currently in the pipeline.

Because they are generally administered in the home setting by a patient or caregiver, over an extended period, it can be easy for the administration, storage and disposal hazards associated with oral chemotherapy to be misunderstood. There are generally more significant safety issues—for both patient and provider—associated with the administration of infused chemotherapy, but a cancer therapy delivered in tablet or capsule form is not without its own exposure risks.

A 2011 report from an international expert panel of pharmacists on the safe handling of oral chemotherapeutic agents, published in the Journal of Oncology Practice, found that none of then-current guidelines for the handling of oral chemotherapeutic agents addressed all of the areas the panel deemed critical for the safe management of these agents (2011;7[1]:7-12).

“With infused chemotherapy, 99% of the time the product is in the custody of a trained health care professional who knows how to handle it, whether it’s the pharmacy preparing it or a nurse, or even a physician in the infusion suite or doctor’s office,” said Rinku Patel, PharmD, RPh, the founder and CEO of KloudScript, an Oakbrook Terrace, Ill.– based firm that offers specialty pharmacy consulting services to retail pharmacies. “Orals are completely opposite.

Once they leave the pharmacy and are in patients’ hands, they are no longer in a controlled environment, and there is a risk that anything could happen,” added Dr. Patel, who is a member of the expert panel.

For that reason, experts say, careful education and counseling from a specialty pharmacist on the potential hazards associated with having oral oncolytic agents in the home are extremely important. “It is important for the specialty pharmacist to spend time talking

Web Exclusive Safe handling of oral chemotherapy can be a challenge. But what about chemotherapy infusions— especially those given in a home care setting? Experts, including one from the National Home Infusion Association, offer their tips for protecting patients and d caregivers.

with the patient and/or caregivers about safe handling of oral anticancer agents in the home,” said Lisa Holle, PharmD, BCOP, an assistant clinical professor of pharmacy practice at the University of Connecticut School of Pharmacy, in Storrs, and current chair of the Hematology/Oncology Pharmacy Association’s (HOPA) Health Policy Committee, who spoke at HOPA’s May 2015 meeting in Austin, Texas, on the importance of following protocols to reduce the risks associated with handling, storage and disposal of oral anticancer agents.

“Counseling the patient about safe administration is something a pharmacist is taught to do for all drugs, but pharmacists need to be aware that oral

therapy. Some precautions that specialty pharmacists should counsel patients and caregivers to take include: Washing hands before and after taking medications. “It’s not an additional risk to patients because they are, obviously, taking the medications themselves,” said Rowena (Moe) Schwartz, PharmD, BCOP, the director of clinical content and services at McKesson Specialty Health in Texas. “But imagine the patient took it, handled it, and then touched a child or handled household stuff, like food. Or the dog licked their hand. The cumulative effect is what would really matter, but even small doses of significantly cytotoxic medications could impact others.”

Avoiding storing anticancer pills or capsules in the commonly used “day of the week” organizers. “That’s concerning because it increases the exposure risk for anyone touching any of those pills,” Dr. Schwartz said. “If the patient or caregiver likes to use those

‘We currently have no real national guidelines for the safe disposal of oral chemotherapy.’

—Lisa Holle, PharmD, BCOP chemotherapy may have additional special considerations related to handling and administration,” Dr. Holle told Specialty Pharmacy Continuum. “Therefore, additional time should be allotted for appropriate patient education to ensure patient safety during therapy.”

The primary hazard with most oral chemotherapy is cytotoxicity, but other drugs, such as lenalidomide (Revlimid, Celgene) and other thalidomide derivatives, also pose risks. “It is important that these potentially hazardous drugs not be accidentally ingested or exposed on the skin,” Dr. Holle said.

“The patient should either administer it themselves, or if the help of a caregiver is needed, that person should wear protective gloves. This is most important with the cytotoxic therapies, but if, for example, a caregiver were a young woman trying to get pregnant and the patient’s drug were teratogenic, gloves would be very important.”

Polypharmacy Confusion Because many people with cancer are also taking other medications, such as antihypertensives or cholesterol treatments, that do not pose risks with administration or storage, they may be in the habit of handling their drugs with less caution than required by chemo-

organizers, the cancer medications should have a separate one.”

People who are accustomed to simply taking their medications with them in a purse should also be warned against casually transporting and handling these drugs, she added.

Understanding the exact handling instructions for each agent. “Some oral anticancer drugs cannot be opened and need to be maintained in the container they are shipped in, for example,” Dr. Schwartz said. “Other agents cannot be crushed; this is essential to know because some people who have trouble taking pills will crush their medications.”

Taking precautions with body waste. Chemotherapy medication is released from the body through urine, stool, vomit and blood. Toilet lids should be closed before flushing (double flushing is advised), and men should urinate sitting down to avoid splashing. Gloves should be worn when cleaning the toilet or cleaning up any vomit or blood.

Provider Precautions Oral chemotherapy frequently is dispensed fully prepared and packaged by the manufacturer, so there are fewer exposure risks to specialty pharmacists and other health care providers than with infused agents that must be mixed and

prepared at the point of care. However, the expert panel advised pharmacists to take a number of precautions, including: • using personal protective clothing and equipment.

• using disposable gloves, with handwashing before and after glove application when dispensing.

• using personal protective equipment that is disposable to the extent possible when performing compounding, crushing, cutting or splitting in a biological safety cabinet.

• limiting unnecessary handling of hazardous medications by other health care professionals. For example, when powdered oral chemotherapeutic agents must be reconstituted in solution, they should be prepared in the pharmacy and placed in an oral syringe ready for administration.

• maintaining a written emergency plan in the event of a spill or accidental exposure.

• maintaining separate equipment and storage for cytotoxic and noncytotoxic agents, and avoiding dispensing oral chemotherapeutic agents using automated counting machines.

Disposal Difficulties When the time comes for disposal of oral chemotherapy—either because the patient has died, toxicity has become unacceptable, the drugs have lost their effectiveness or because the course of treatment has ended—patients and families have few good options, Dr. Holle noted. “We have no real national guidelines for the safe disposal of oral chemotherapy,” she explained. “Disposal of hazardous drugs is generally governed by state environmental protection agencies. But once a medication is dispensed to a patient, it is actually considered a household waste and therefore falls under different regulations in terms of who manages the waste and how it can be disposed.”

Household waste management is exempted under the Resource Conservation and Recovery Act (RCRA), the primary U.S. federal law that governs the disposal of hazardous wastes and classifies drugs by their relative hazards. Some cytotoxic oral cancer therapies technically fall under RCRA, but because they are household waste, they are exempt.

So where does that leave patients and their families? “If the drugs were directly dispensed by a pharmacy or a cancer clinic to the patient, they can be returned there, but if they were mailed to you, you cannot mail a hazardous product back,” Dr. Holle said.

Policies vary by state, but many states do not permit pharmacies to accept the

5

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

IG SELECTION continued from page 3

subcutaneously. However, there was no subcutaneous version of the 10% IVIG product the patient was taking. Thus, a conversion from that IVIG product to an available subcutaneous formulation needed to be calculated. The dose for the 10% product is not the same as the IV version, so 400 mg/kg at 100 kg=40 g IV. For subcutaneous administration, the dose is multiplied by 1.37 or 548 mL. This can be given weekly or 137 mL per week. If given in 4 sites (35 mL/site) at a maximum rate of 20 mL per hour per site, the total duration of infusion is approximately 2 hours and will require an infusion pump, proper tubing, and training. Provided that the patient is able to perform this type of infusion and get insurance coverage approval, there are many advantages to

disposal of hazardous drugs if they did not dispense them. In the spring of 2015, Dr. Holle completed a pilot program that allowed patients to return their unused cancer drugs to the University of Connecticut Health Center. “It was very successful, but while we are waiting for the state to review our pilot, I now have to tell patients not to put their unused drugs into the trash or flush them, but just to hold onto them until— hopefully—I can take them back. That’s an added burden on them.”

Dr. Holle presented her pilot project at the HOPA meeting in May, and she noted that many U.S. practitioners in the audience were dealing with similar issues and inquired about starting their own pilots. “Our international colleagues were dumbfounded that we couldn’t do this without a regulation change,” she said.

“Any pharmacy, physician’s office or hospital—any place that is already generating and collecting hazardous waste—would be the obvious choice for disposal of these medications, since they have the policies and procedures in place already.”

Some further guidance on these issues may soon be at hand: At press time, the Environmental Protection Agency (EPA) issued new proposed rules aimed at improving the handling of pharmaceutical waste. Part of the updated information is intended to prevent the introduction of more than 6,400 tons of hazardous waste pharmaceuticals into the nation’s waterways annually by banning health care facilities from flushing these materials down the sink and toilet, according to an EPA press release.

However, the new proposed rules do not address hazardous drug handling in the home, and they don’t address oral chemotherapy agents specifically, as a subclass of oncolytic agents.

—Gina Shaw

this approach, including the likelihood of better tolerance, home infusion, less time of infusion, and improved and independent lifestyle.

Another subcutaneous option is to select the one 20% subcutaneous product that is currently available and give it once every 2 weeks at the same dose with 4 injection sites over 2 hours. The physician decides to select this option because 2 of the 10% options were the same product that was associated with the suspected aseptic meningitis episode.

The patient tolerates the new sub-

cutaneous regimen quite well but has some discomfort and swelling of the injection sites. The headache is gone and no premedications are needed.

Other Options There is one additional treatment strategy to employ if a patient such as the one described above is not able to tolerate a subcutaneous regimen or becomes noncompliant. Specifically, it is a combination of a 10% IG product with hyaluronidase as a subcutaneous infusion. For this patient it would be

a 1:1 conversion or 40 g once every 4 weeks as a continuous subcutaneous infusion. Although the details of the ramp-up are too detailed for this FAQ, the process for conversion is specific for conversion from IV or subcutaneous to this new form of therapy, which provides both the advantages of IV and subcutaneous therapy.

■ Dr. Siegel disclosed that he is on the advisory board for Baxalta, has developed educational materials for Kedrion and conducted research for CSL Behring.

6

Specialty Pharmacy Continuum • September/October 2015

CLINICAL D IS EASE ST A T E S P O T L I GH T

PCSK9 Inhibitors:

A New Rx Paradigm for Severe Hyperlipidemia cardiovascular disease (CVD), including myocardial infarctions (MIs) or strokes, who require additional lowering of LDL cholesterol.8,9

C. Michael White, PharmD, FCP, FCCP Professor and Chair University of Connecticut School of Pharmacy Storrs, Connecticut

Efficacy and Safety

The proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors offer a major advancement in the treatment of hypercholesterolemia in patients who cannot tolerate or who do not achieve sufficient low-density lipoprotein (LDL) reduction with statin therapy, especially those patients with familial hypercholesterolemia (FH). In this educational review, we review the current state of hypercholesterolemia management, pharmacology and clinical outcome data for PCSK9 inhibitors, and the role of this class in contemporary care.

Current State of Care The National Cholesterol Education Program (NCEP) guidelines, in effect through 2013, recommend achieving an LDL cholesterol level commensurate with the patient’s baseline risk for cardiac disease.1 According to the guidelines, patients diagnosed with cardiac disease or who are in the highest-risk group for the condition should be treated to a target LDL less than 100 mg/dL, although a level less than 70 mg/dL was acceptable. Patients with moderate or low cardiac disease risk, in contrast, had to achieve LDL levels less than 130 or 160 mg/dL.2 The NCEP stopped producing guidelines, and the new American Heart Association (AHA)/American College of Cardiology (ACC) treatment guidelines, published in 2013, stressed the preeminence of statin therapy with a dosing intensity dictated by a patient’s cardiovascular risk.2 When the new AHA/ ACC treatment guidelines were written, there were no compelling data showing that medications aside from statins had robust ability to reduce cardiovascular events. Moreover, concomitant niacin and fibrate therapy were unable to add additional benefits over statins alone.3-5

es LDL concentrations. The PCSK9 inhibitors are monoclonal antibodies that prevent PCSK9 from binding LDL receptors and prolong their effective life, which consequently reduces LDL concentrations.6,7 Among the PCSK9 inhibitors that have been discovered, alirocumab (Praluent, Sanofi/Regeneron) and evolocumab (Repatha, Amgen) were approved by the FDA in July and August 2015, respectively.8,9 Both agents are indicated for lipid lowering as an adjunct to diet and maximally tolerated statin therapy in adult patients with FH. The drugs are also indicated for patients with clinical atherosclerotic

Table. Lipid, Cardiovascular, and Safety Outcomes With PCSK9 Therapy Lipid Outcomes LDL a

Alirocumab

TC

HDL

Tri

Non-HDL

–61.9% (P<0.001)

–37.5% (P<0.001)

+4.6% (P<0.001)

–17.3% (P<0.001)

–52.3% (P<0.001)

Evolocumabb –61.0% (P<0.001)

–36.1% (P<0.001)

+7.0% (P<0.001)

–12.6% (P<0.001)

–52.0% (P<0.001)

Cardiovascular Outcomes (Drug vs Control, P Value) MACE

CHD Death

MI

Stroke

Unstable Angina

Alirocumaba

1.7% vs 3.3% (P=0.02)

0.3% vs 0.9% (P=0.26)

0.9% vs 2.3% (P=0.01)

0.6% vs 0.3% (P=0.35)

0% vs 0.1% (P=0.34)

Evolocumabb

1.0% vs 2.1% (P=0.003)

0.1% vs 0.2% (P=NR)

0.3% vs 0.3% (P=NR)

0.1% vs 0.1% (P=NR)

0.1% vs 0.2% (P=NR)

PCSK9 Pharmacology The LDL receptors are created and expressed on the surface of hepatocytes. The receptors bind LDL and then undergo a recycling event whereby they are internalized, the LDL is detached from the LDL receptor, the LDL receptor reemerges on the cell surface, and the LDL is broken down.6,7 The PCSK9 inhibitors bind to an LDL receptor and prevent it from being recycled after they bind LDL and are internalized.6,7 This reduces the average life span of LDL receptors in the body and increas-

The Table displays the lipid, cardiovascular outcome, and safety comparisons for the 2 FDA advisory panel–reviewed PCSK9 inhibitors versus controls.10,11 The Table is derived from data from the 2 largest PCSK9 assessments conducted to date. The ODYSSEY LONG TERM trial included 2,341 patients who were given statins at their maximum tolerated dose before being randomly assigned to alirocumab (150 mg every 2 weeks for 78 weeks) or matching placebo. The OSLER-1 and OSLER-2 (Open-Label Study of Long-Term Evaluation Against LDL-C) trials included 4,465 patients who received evolocumab 140 mg every 2 weeks or 420 mg monthly plus standard therapy versus standard therapy alone; 70% of the patients received statins, and 13% to 15% received ezetimibe (Zetia, Merck). In both trials, the LDL was reduced from a baseline LDL of approximately 120 to 48 mg/dL (median followup, 11 months).10,11 Like statins, PCSK9 inhibitors have a potent ability to lower LDL with modest triglyceride lowering and high-density lipoprotein (HDL)-raising effects.10,11 The LDL lowering is greater than the

15% to 25% lowering achieved with ezetimibe, the bile acid sequestrants, and niacin.12 Non-HDL cholesterol includes LDL and very low-density lipoprotein (VLDL). In previous NCEP guidelines, the non-HDL goal was set 30 mg/dL above the LDL goal to account for the atherogenic contribution of VLDL. The PCSK9 inhibitors affect non-HDL and total cholesterol (LDL+VLDL+HDL) concentrations primarily through their LDL-lowering effects.10,11 In patients with homozygous FH, the LDL reductions of 30.9% ((P<0.001) with evolocumab versus placebo in the TESLA-B trial were not as robust as in patients with heterozygous FH or no genetically determined FH but in line with that seen with other drugs approved for homozygous FH, such as lomitapide (Juxtapid, Aegerion) and mipomersen (Kynamro, Genzyme).12,13 Major clinical trials have been designed to assess cardiac and cerebrovascular events, as prespecified primary outcomes will not be reported for another couple of years.10,11 In the ODYSSEY LONG TERM and OSLER trials, the incidence of major adverse cardiovascular events (composite including death and major coronary and cerebrovascular events) was significantly reduced. However, stroke (another composite end point assessed) did not seem to be reduced by either PCSK9 inhibitor, and the power to discern dif-

Safety Outcomes Any ADE

Serious ADE

Injection-Site Reaction

Muscle Related

Neurocognitive Event

Alirocumaba

81.0% vs 82.5% (P=0.40)

18.7% vs 19.5% (P=0.66)

5.9% vs 4.2% (P=0.10)

5.4% vs 2.9% (P=0.006)

1.2% vs 0.5% (P=0.17)

Evolocumabb

69.2% vs 64.8% (P=NR)

7.5% vs 7.5% (P=NR)

4.3% vs NR (P=NR)

6.4% vs 6.0% (P=NR)

0.9% vs 0.3% (P=NR)

ADE, adverse drug event; CHD, coronary heart disease; HDL, high-density lipoprotein; LDL, low-density lipoprotein; MACE, major adverse cardiac events; MI, myocardial infarction; NR, not reported; PCSK9, proprotein convertase subtilisin/kexin type 9; TC, total cholesterol; Tri, triglycerides a

Results derived from the ODYSSEY LONG TERM trial.

b

Results derived from the combined OSLER-1 and OSLER-2 (Open-Label Study of Long-Term Evaluation Against LDL-C) trials.

7

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

ferences between the other components was low.10,11 However, alirocumab significantly reduced nonfatal MIs versus placebo.10 Although these results are promising, these data are not strong enough to allow firm conclusions about the final health outcome benefits of PCSK9 inhibitor therapy.

One of the benefits of the PCSK9 inhibitors is their safety profile.6,7 In the ODYSSEY LONG TERM and OSLER combined trials, the overall incidence rates of adverse events and serious adverse events for the PCSK9 inhibitor and control groups were similar.9,10 Equally important, the incidence rates of creatine kinase and liver transaminase elevations over 3 times the upper limit of normal were not greater than control, indicating that PCSK9 inhibitors do not adversely affect muscles or liver function.10,11 This is an important finding, because muscle toxicity has been shown to be a potential adverse effect (AE) of statin therapy.12 Muscle toxicity also has been observed in patients treated with mipomersen and lomitapide, leading to a Risk Evaluation and Mitigation Strategy program for both medications.12 Certain statins and niacin can induce liver toxicity as well.12 While not powered to detect differences between groups, the most commonly reported AEs in the ODYSSEY LONG TERM and OSLER combined trials included local site-injection reactions in 4% to 6% of patients, myalgia in 5% to 6% of patients, and neurocognitive adverse events (delirium, memory impairment, confusional state, amnesia) in 1.0% to 1.2% of patients.10,11 More work needs to be conducted to evaluate the neurocognitive adverse events of the PCSK9 inhibitors in the general hypercholesterolemia population following approval.

Ezetimibe and bile acid sequestrants are other adjuvant agents to combine with a statin that have strong safety profiles.12

Pharmacists' Role The PCSK9 inhibitors are very promising agents in the armamentarium against hypercholesterolemia.6,7,10,11 With the positive results of the aforementioned PCSK9 inhibitor studies and the IMPROVE-IT trial with ezetimibe, there is increased impetus to measure LDL concentrations and achieve LDL goals that are aggressive with combination therapy.14 The IMPROVE-IT trial found that further suppression of LDL with simvastatin 40 mg plus ezetimibe 10 mg daily was associated with significant improvements in composite cardiovascular events versus simvastatin 40 mg daily alone. This was the first trial to show that combination therapy to achieve more aggressive LDL reduction than with a statin alone could produce additional cardiovascular benefits.14 Changing back from a drug- and dose-driven guideline

MJ, Haynes R, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203-212.

6. Norata GD, Tibolla G, Catapano AL. PCSK9 inhibition for the treatment of hypercholesterolemia: promises and emerging challenges.

Vascul Pharmacol. 2014;62(2):103-111.

7.

Cicero AF, Tartagni E, Ertek S. Safety and tolerability of injectable lipid-lowering drugs: a review of available clinical data. Expert Opin Drug Saff 2014;13(8):1023-1030.

8. Praluent [package insert]. Bridgewater, NJ: Sanofi/Regeneron; July 2015.

to an LDL goal–derived guideline is now evidence based but would be a major shift in practice, of which pharmacists have an important direct patient care role. Pharmacist-directed or -supported lipid and CVD clinics have been shown to help more people reach target LDL goals than standard practices.15 Patients with or at the highest risk for CVD should likely achieve an LDL level less than 70 mg/dL, whereas those with moderate risk should achieve an LDL level less than 100 mg/dL.1,10,11,14,16-18 Moreover, patients starting PCSK9 inhibitors will need to understand how to administer a subcutaneous injection, and pharmacists, with their certifications for immunizations, are increasingly prepared to counsel them on safe use.

Patients will need to be followed closely to ensure they are achieving their LDL goals and modifying therapy accordingly.

Weighing the Evidence Ezetimibe has stronger outcome data than the PCSK9 inhibitors, and both medications have a strong safety profile.

It thus seems intuitive that ezetimibe be the preferred adjunctive therapy.10-12,14 It also has a much lower drug acquisition cost and a more convenient oral dosage form. However, ezetimibe has a limited ability to reduce LDL, and if patients require more than 20% reductions in LDL to achieve their goals, PCSK9 inhibitors can be a preferable option.10-12 Niacin and fibric acid derivatives have data showing a lack of additional final health outcome benefits when added to statins and a less favorable safety profile in patients with hypercholesterolemia, and would not be competitive options.3-5,12 In those patients who cannot tolerate statins, PCSK9 inhibitors with or without ezetimibe can be an acceptable alternative combination regimen that can provide acceptable lipid effects with a strong safety profile.6,7 In patients with homozygous FH, PCSK9 inhibitors have distinct liver safety advantages over mipomersen and lomitapide with similar lipid benefits.12,13 As such, PCSK9 inhibitors could be used preferentially over these other options. In the single trial assessing evolocumab in homozygous FH, triple therapy with PCSK9 inhibitors, statins, and ezetimibe was shown to be effective and will likely be needed in

most patients.13 In this trial, patients who could not produce functional LDL receptors (LDL-negative mutations on both alleles) or those with autosomal recessive hypercholesterolemia did not derive LDL reductions, and should not be given PCSK9 inhibitor therapy.13 Dr. White reported no relevant financial conflicts of interest.

9. Repatha [package insert]. Thousand Oaks, CA: Amgen Inc; August 2015.

10. Robinson JG, Farnier M, Krempf M, et al; for the ODYSSEY LONG TERM Investigators.

Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1489-1499.

11. Sabatine MA, Giugliano RP, Wiviott SD, et al.

Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372(16):1500-1509.

12. White CM. MTM essentials for cholesterol management. Drug Topics. 2014;2:64-72.

References 1. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;106(25):3143-3421.

2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1-S45.

3. ACCORD Study Group, Ginsburg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010;362(17):1563-1574.

4. AIM-HIGH Investigators, Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255-2267.

5. HPS2-THRIVE Collaborative Group, Landray

13. Raal FJ, Honarpour N, Blom DJ, et al. Inhibition of PCSK9 with evolocumab in homozygous familial hypercholesterolemia (TESLA Part B): a randomized, double-blind, placebo-controlled trial. Lancet. 2015;385(9965):341-350.

14. Cannon CP, Blazing MA, Guigliano RP, et al. Ezetimibe added to Statin therapy after acute coronary syndromes. N Engl J Med. 2015;372(25):2387-2397.

15. White CM. Pharmacists need recognition as providers to enhance patient care. Ann Pharmacother. 2014;48(2):268-273.

16. Cannon CP, Braunwald E, McCabe CH, et al.

Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350(15):1495-1504.

17. LaRosa JC, Grundy SM, Waters DD, et al.

Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352(14):1425-1435.

18. Ridker PM, Danielson E, Fonseca FA, et al.

Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195-2207.

FDA APPROVALS

Two New PCSK9s for Lipid Lowering

T

he FDA has approved two new PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors for severe hypercholesterolemia.

Evolocumab (Repatha, Amgen), approved in August 2015, is indicated for use in adults with familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of LDL cholesterol (LDL-C), according to the FDA. In a Phase III trial, 90% of ASCVD patients who received evolocumab in addition to maximum doses of statins achieved an LDL-C level less than 70 mg/dL. Hypersensitivity reactions (e.g., rash, urticaria) have been reported in patients treated with evolocumab, including some that led to discontinuation of therapy.

Alirocumab (Praluent, Sanofi/Regeneron), approved in July 2015, is also approved for use in adults with familial hypercholesterolemia or ASCVD, according to the FDA. Patients in trials submitted to the agency had an average reduction in LDL-C ranging from 36% to 59%, compared with placebo. Allergic reactions, such as hypersensitivity vasculitis and hypersensitivity reactions requiring hospitalizations, have been reported with use of alirocumab.

8

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

Simple But Effective Rx for HIV-HCV Coinfection The combination of two new drugs to treat hepatitis C infection may be the ideal regimen to control the condition in patients who also have HIV, researchers have found.

The NS5A inhibitor daclatasvir (DCV; Daklinza, Bristol-Myers Squibb) and the nucleotide NS5B inhibitor sofosbuvir (SOF; Harvoni, Gilead) appeared to be most effective at three months for patients with both HIV and hepatitis C virus (HCV), according to a study presented at the 2015 Digestive Disease Week (DDW) in Washington, D.C. At the end of the 12-week study (abstract 901d), the team observed a sustained virologic response (SVR12) in 97% of enrolled patients, and response rates were similar across HCV genotypes, in patients with or without cirrhosis, and regardless of whether patients received prior HCV therapy.

“There was no compromise of HIV control or modifications required of antiretroviral treatment,” said Kenneth Sherman, MD, the director of the Division of Digestive Diseases at the University of Cincinnati College of Medicine, who also noted that there were no discontinuations or serious adverse events.

The open-label ALLY-2 study included 151 HIV patients randomly assigned in a 2:1 ratio to receive eight or 12 weeks of DCV-SOF. If taking combi-

nation antiretroviral therapy (cART), HIV RNA had to be less than 15 copies/mL with a CD4 count greater than 100 cells/mm2. In those patients not on cART, CD4 counts greater than 350 cells/mm2 were required. The 52 treatment-experienced patients, who were allowed any prior HCV therapy except an NS5 inhibitor, received 12 weeks of DCV-SOF. All but four patients in this study were on cART. Standard doses of DCV and SOF, which are 60 and 400 mg, respectively, were adjusted when appropriate to HIV regimens. Specifically, 30 mg of DCV were employed in patients receiving a ritonavir (Norvir, AbbVie)-boosted protease inhibitor, whereas 90 mg were used in combination for all non-nucleoside reverse transcriptase inhibitors except rilpivirine (Edurant, Janssen).

The eight-week regimen was generally less effective. The overall SVR12 rate in this arm of the study was 76%, with particularly low response rates observed in those with cirrhosis (60%), genotype 1b (50%) and genotype 3 (67%). However, Dr. Sherman noted that this is the first large trial to evaluate a regimen

of less than 12 weeks in patients with HCV-HIV coinfection. He reported that SVR12 rates climbed in the eight-week arm among those with relatively low HCV viral load at baseline.

On 12 weeks of DCV-SOF, response rates were more uniform in treatmentnaive and -experienced patients. The SVR12 rates of 100% were achieved in several subgroups, including those with genotypes 1b, 2, 3 or 4. For those with cirrhosis, rates appeared to be slightly lower, but numbers were small. The SVR12 was achieved in eight of nine (89%) of the treatment-naive patients treated for 12 weeks and in 14 of 15 (93%) of the treatment-experienced patients. There was no clear difference in response rates according to gender, age or race.

One attribute of DCV and SOF, according to Dr. Sherman, is that each imposes a low propensity for drug–drug interactions. He noted that DCV-SOF achieves very high SVR12 rates, particularly when administered over 12 weeks “across a broad range of cART regimens without compromising HIV control.”

“The results of the study suggest that this combination is versatile in the setting of coinfection,” said Paul Y. Kwo, MD, a medical professor of gastroenterology/hepatology at Indiana University–Purdue University Indianapolis, who also presented a late-breaker trial in

HCV therapy at the DDW meeting. “The ALLY-2 study demonstrates that the combination of daclatasvir and sofosbuvir for 12 weeks is an effective treatment of HIV-hepatitis C patients with genotypes 1 through 4 regardless of treatment history or disease severity,” observed Dr. Kwo. According to ALLY-2, he noted, the DCV-SOF combination “could be used with a wide range of antiretroviral medicines, and is an important addition to our therapeutic armamentarium for treating coinfected individuals.”

—Ted Bosworth Dr. Sherman reported financial relationships with Abbott, Boehringer Ingelheim, BristolMyers Squibb, Genentech, Gilead, Kadmon, Merck, Novartis, Medpace, Tibotec/Janssen and Vertex. Dr. Kwo reported financial relationships with Abbott, AbbVie, BristolMyers Squibb, Gilead, Janssen and Merck.

Spike in HCV Cases Creates Tough Treatment Choices Recently Mark S. Sulkowski, MD, of the John Hopkins University School of Medicine, in Baltimore, saw a teenage patient who had contracted hepatitis C virus (HCV) after starting to shoot up as a 12-year-old.

The case is but one in a spike of new infections with HCV being driven largely by an epidemic of injection drug use (IDU), particularly among adolescents and young adults, according to the Centers for Disease Control and Prevention.

“Sadly, with the heroin epidemic, I’m increasingly seeing teenagers in my practice,” Dr. Sulkowski said earlier this year at the inaugural midyear meeting of the American Association for the Study of Liver Diseases in Chicago.

Although mother-to-child transmission remains the primary source of HCV infection for children, IDU is a common source of infection for adolescents (Clin Liver Dis 2014;5:14-16).

Managing young patients is challenging for clinicians, who may not be accustomed to treating pediatric patients and who have little data to guide their treatment decisions.

“This is a patient population for whom

data are lacking,” Dr. Sulkowski said.

Dr. Sulkowski said there was a nine-year gap between the publication of the first clinical trials of pegylated interferon and ribavirin in adults and similar studies in children ((N Engl J Med d 2002;347[13]:975982). As a result, investigators were uncertain of a safe dose and whether the medications would affect growth or pose other risks to children, he said. However, eventually results suggested that the combination also worked in children.

When it comes to the newer directacting antiviral (DAA) agents, such as sofosbuvir (Solvadi, Gilead), however, no such clarity is at hand: Studies of DAAs are underway in pediatric populations, but none have been published so far, according to Maureen Jonas, MD, the clinical director of the Center for Childhood Liver Disease at Boston Children’s Hospital. Pediatric trials are more complicated because appropriate

doses for children of different ages and sizes must be determined, Dr. Jonas said. Children also may be unable to swallow large pills, requiring a different means of administration.

So far, Dr. Jonas said there is no reason to believe that children will not experience cure rates above 90% with 12 weeks of DAA therapy, as do adults.

That prospect makes alternative drugs currently FDA approved for younger patients, such as such as pegylated interferon and ribavirin, an unappealing option, because they may require a year-long regimen and only be curative in about half of cases, she said.

“It’s hard to justify treating children with the currently approved medications,” Dr. Jonas stressed.

With data on DAAs on the horizon, Dr. Jonas recommended postponing treatment until new medications are approved

for pediatric patients. A few exceptions in whom treatment might be appropriate, she noted, are children in countries where DAAs are unlikely to become available and patients with genotype 2 or 3 HCV, which are susceptible to 24 weeks of treatment with older drugs. For patients with advanced liver disease, currently available drugs almost certainly will not work well.

Health insurers are unlikely to cover off-label use of costly DAAs approved by the FDA for adults, Dr. Jonas said. Even if coverage were available, appropriate doses have yet to be determined. For now, the only options for treating pediatric patients who cannot wait for new drugs are those currently approved by the FDA for pediatric use.

However, Dr. Jonas acknowledged that with ads promoting the effectiveness of DAAs for adults, it might be a challenge to explain to parents why the treatments are not yet available for children and adolescents.

“It’s just as hard to tell families with children we want to wait,” she said.

—Bridget M. Kuehn

75 YEARS OF IMPROVING THE HEALTH & WELL-BEING OF PEOPLE WORLDWIDE At Grifols, we are proud of our pioneering spirit and history of innovation. In 1940, we founded a company that has helped transform hematology.

Today, we are a global leader providing life-saving protein therapies, diagnostic solutions, and other tools that hospitals, pharmacies, and healthcare professionals need to deliver expert medical care.

Your partner in the management of CIDP and PIDD patient care

Learn more about Grifols at www.grifols.com

10

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

Rapid Growth, New Drugs Eyed for Hemophilia Las Vegas—“Write this prediction down and see if it comes true,” declared Hetty Lima, RPh, FASHP, recently retired as vice president of specialty infusion services and rare diseases at Diplomat Specialty Pharmacy, at the 2015 Armada Specialty Pharmacy Summit.

“Payors are going to start managing the hemophilia drug class much like they’ve done with other disease states such as growth hormone, multiple sclerosis and rheumatoid arthritis, with preferred products.”

Hemophilia, which the National Hemophilia Foundation estimates to affect approximately 20,000 Americans, is actually growing faster as a drug class than medications for these more common conditions, Ms. Lima said. The disorder’s 16.9% overall cost increase over the past year is driven largely by a 17.6% increase in unit factor cost.

“It’s the eighth most expensive specialty class when ranked by per-member, per-year cost,” she said, citing the Express Scripts 2014 Drug Trend Report (http://lab.express-scripts.com/drugtrend-report). Additionally, the mean

expenditure per hemophiliaa patient in the commercial population is $155,000 annually, and $697,000 annually for patients with inhibitors ((Haemophilia 2012;18[2]:268-275).

Prior to 2014, there were no long-acting clotting factors for hemophilia. Then, in a one-two punch, Biogen Idec won FDA approval for Alprolix (recombinant factor IX fusion protein) for hemophilia B in March 2015, and Eloctate (recombinant factor VIII Fc fusion protein) did the same for hemophilia A in June 2015.

These drugs can be taken much less frequently than other recombinant clotting factors—once every three to five days for Eloctate, and once weekly or less for Alprolix, compared with three times weekly for other clotting factors.

Both of these drugs dramatically reduce bleeding episodes when taken

prophylactically, said Sheh-Li Chen, PharmD, BCOP, a clinical pharmacy specialist in benign hematology at the University of North Carolina Medical Center in Chapel Hill, and an expert on coagulation disorders, in a separate Armada session. “Eloctate showed a reduction in the annualized bleed rate [ABR] of 92% in the individualized prophylaxis arm, and 76% in the weekly prophylaxis arm compared with the episodic treatment arm, while Alprolix had a reduction in ABR of 87% in the fixed weekly interval group and 87% in the individualized interval group compared with episodic treatment.”

In December, Baxter—which has long held dominance in the hemophilia market—filed its biologics license application with the FDA for its own extended-

life hemophilia A factor, BAX 855. Both Bayer and Novo Nordisk have their own long-acting clotting factor drugs in the pipeline. This heightened degree of drug development “is a game changer in therapeutic management of hemophilia,” Ms. Lima said. “We’re going from a drug class that had very few products to one that’s expanding quite rapidly.”

More Rx Options For Payors A plethora of long-acting hemophilia factors on the market will give payors room to manage utilization with preferred products—but more importantly, it will also offer specialty pharmacies greater opportunities to work with patients on prophylactic management of their condition and improve adherence to treatment, experts noted.

More Choice for Physicians Treating AHA A The recent FDA approval of antihemophilic factor (Recombinant), porcine sequence (Obizur, Baxter) to treat acquired hemophilia A (AHA) provides clinicians more opportunity to help patients with this rare bleeding disorder, said Annette von Drygalski, MD, PharmD, the director of the Hemophilia and Thrombosis Treatment Center at the UC San Diego Health Sciences.

Acquired hemophilia A is caused by the spontaneous development of antibodies, called inhibitors, directed against the body’s own factor VIII (FVIII) in individuals with previously normal hemostasis, Dr. von Drygalski said. Unlike inherited hemophilia, AHA is an autoimmune disease that can affect men and women, most often postpartum women and the elderly with malignancies.

Because there is no family history of hemophilia and the condition is very rare (about one in 1 million individuals), AHA is not often included in a physician’s differential diagnosis. Frequently, the condition is identified because of excessive bleeding postpartum or during surgery. The bleeding can be profound, according to Dr. von Drygalski, and in some cases, fatal.

Obizur is the first treatment approved

for AHA that allows clinicians to manage the treatment’s efficacy and safety by measuring FVIII activity levels in additional to clinical assessments, according to the FDA.

In all, 86% (24 of 28) had successful treatment of the initial bleeding episode.

Obizur contains a recombinant analog of porcine FVIII, which is used because it is similar enough to human FVIII to be effective in blood clotting, but is less susceptible to inactivation by circulating human FVIII antibodies.

Before Obizur’s approval, AHA was treated with activated prothrombin complex concentrate or recombinant factor

VIIa, due to the agent’s ability to reduce bleeding without the need for FVIII, said Dr. von Drygalski, who treats about one or two AHA patientss a year. Factor VIII is not typically useed in AHA because it is often inefficieent e in the presence of antibodies directed against FVIII. These drugs, known as bypassing agents because they bypass the FVIII inhibitor to allow thrombin generation and clot formation, have some “drawbacks,” she said, most notably a higher risk for thromboembolic events.

Additionally, “not everyone responds to bypassing agents,” she stressed.

The safety and efficacy of Obizur was evaluated in a global, prospective, controlled, multicenter, Phase II/III open-label clinical trial (N=29 patients).

All of the patients treated with Obizur showed a positive response, meaning an effective or partially effective response with bleeding stopped or reduced and clinical improvement at 24 hours after the initial infusion.

In all, 86% (24 of 28) had successful treatment of the initial bleeding episode.

The investigator determined the overall treatment success based on the ability to discontinue or reduce the dose and/or dosing frequency of Obizur.

The most common adverse reaction

observed in more than 5% of 29 patients was the development of inhibitors to porcine FVIII. “However, it is my understanding that even if patients [developed] cross-reactive antibodies that also neutralized Obizur, it may still be efficacious in stopping a significant amount of bleeding in patients,” Dr. von Drygalski said, if target FVIII activity levels are reached.

However, the Baxter studies did not rechallenge those who developed inhibitors, so this is not confirmed by data.

Other than monitoring, no special steps must be taken to switch factors. “If the patient is not responding to one, you can [switch to another agent],” she said.

“This is a really rare form of hemophilia,” she added, so it is good to have “more opportunities to really help patients with bleeding, especially those who have not responded to conventional bypassing.”

—Marie Rosenthal Dr. von Drygalski has received research grants from Baxter.

11

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

“Pharmacists have a very important role in the management of patients with hemophilia,” Dr. Chen said. “Often, the patient [or the patient’s parents, in the case of young children with hemophilia] will share more with their pharmacist than they will with their physician.

If they are struggling to afford their copays, they may not say anything to their physician at the appointment, but they will tell the pharmacist when they pick up their prescriptions.”

Barriers to adherence for hemophilia patients are many, Dr. Chen said. The new long-acting therapies may reduce some of the barriers, such as venous access problems and resistance to frequent injections, particularly among younger patients. But other factors, such as inadequate insurance coverage and the perception that prophylactic therapy is unnecessary or inconvenient—particularly when symptoms fluctuate—require active participation from pharmacists.

Primary prophylaxis—initiated before 3 years of age and before a second joint bleed—is ideal. But specialty pharmacists should know that it’s never too late to start prophylactic therapy for hemophilia, she said. Even if a patient has been receiving therapy for bleeds episodically and has had multiple episodes of bleeding, initiating prophylaxis can have significant benefits. It cannot repair joint damage, but it decreases the frequency of bleeding and can prevent additional progression of damage to the joints.

The SPINART study, published in 2013, is a case in point. The randomized

by the

numbers

controlled, open-label trial assessed older patients aged 12 to 50 years, who had had between six and 24 bleeding events in the previous six months (J ( Thromb Haemost 2013;11[6]:1119-1127).

Patients placed on a three-times-weekly regimen of clotting factor experienced only two bleeding episodes (1.7 joint bleeding episodes) per year, compared with 52.7 bleeding episodes (24.2 joint bleeding episodes) among patients with on-demand therapy.

In addition, these trials used earlier-generation clotting factors that had

more frequent dosing. The 78% mean adherence rate in the prophylaxis group might become significantly improved with access to new, long-acting factors, which could bring bleeding episodes down even more.

“The specialty pharmacist is critical to helping the hemophilia patient and [the] family better understand the importance and benefits of prophylaxis,” Dr. Chen said. “It’s also important to monitor their ability to take their medications correctly and adhere to prescribed prophylaxis. I recommend identifying

The cost of specialty drugs is growing at a rate of 20% per year and at a cost 50 times greater than traditional non-specialty drugs.

A PHS engagement can help your health system to address this opportunity.

The number of patients diagnosed with hemophilia each year.

■

Improved clinical outcomes and patient satisfaction by enhanced coordination of care

20,000

■

Decreased patient “leakage” from health system/ACO to maintain accompanying revenue streams

■

An employee-incentivized specialty benefit program

■

A consultative, scalable approach implemented to meet your specific health systems’ requirements

The number of people currently diagnosed with hemophilia in the U.S.

40% The percent lower mortality and hospitalization rate when hemophilia patients are managed in specialized treatment centers vs. those not receiving such care.

Source: www.cdc.gov/ncbddd/hemophilia/data.html.

Dr. Chen reported receiving research support from Abbott, Gilead Sciences, GSK/ViiV, Illinois Department of Public Health, Janssen, Merck, and speaker’s bureau participation with Kansas Truman Medical Center, Midwest AIDS Training and Education Center. Ms. Lima reported no relevant financial conflicts of interest.

Enhance Patient Care While Realizing New Revenue Streams Specialty pharmaceuticals is one of the fastest growing segments within the pharmaceutical marketplace. According to future-trending reports, specialty drugs will account for the majority of new drug approvals in coming years and will consume approximately 40-50% of health plans’ pharmaceutical spending by 2020.

400

the family member who has the biggest influence on the patient, and making sure that you educate [him or her] as well. It’s very hard for patients to man age all of this alone.”

—Gina Shaw

PHS assists clients to thoughtfully create a program to increase quality of care and deliver efficiency while realizing the substantial revenue streams and cost containment benefits it can provide.

For more information about Pharmaceutical Healthcare Solutions, contact us at 877-892-1254 or email solutions@amerisourcebergen.com

12

Specialty Pharmacy Continuum • September/October 2015

CLINICAL D IS EASE ST A T E S P O T L I GH T

The Pharmacist’s Role in Managing MS Kathleen Love, RN Clinical Program Manager Specialty Pharmacy Walgreen Co. Deerfield, Illinois

Multiple sclerosis (MS) affects roughly 400,000 Americans and more than 2 million people world-wide, making it one of the most common neurologic disabilities.1 In the United States, someone is diagnosed with MS every hour. Due to factors ranging from the high cost of medication to the need for support—such as assistive devices and nursing care—MS management costs in the United States are estimated to be more than $16 billion annually.2 This chronic and progressive autoimmune disorder can be difficult to manage, causing a wide variety of symptoms, ranging from balance and cognitive problems to fatigue and depression. Given the range of symptoms and progressive nature of the disease, management of this patient population can be challeng-

ing, requiring a unique approach that can be provided through a specialty pharmacy provider. Although there is no cure for MS, a number of treatments are available that can slow disease progression or modify its course.

Without treatment, the disease may continue to progress and lead to further, irreversible damage, making adherence crucial. Remaining adherent to treatment regimens can be difficult for patients because most of these medications are complex, requiring injection or infusion, and they sometimes have debilitating side effects. Specialty pharmacists, therefore, can play a key role in helping patients with MS manage their treatment.

A Progressive Disease Multiple sclerosis is more common in women and most often is diagnosed between 20 and 50 years of age.1 The cause of MS is unknown. Although MS has a genetic component, researchers believe that other factors may be involved, including infection, geographic location, and environmental causes.3 In a patient with MS, the body’s

immune system mistakenly attacks the myelin sheath that protects nerve fibers, damaging the central nervous system (CNS)—including the brain, spinal cord, and optic nerves. The resulting demyelination, or scarring, interferes with the ability of the CNS to transmit signals along the nerves. Nerves throughout the

Patient Case

B

T is a 44-year-old woman who was diagnosed with multiple sclerosis (MS) in 2013. On April 16, 2013, she was switched to a disease-modifying therapy (DMT), interferon β-1a (Avonex, Biogen), per initial referral received by a Walgreens Specialty Pharmacy. However, within hours, the prescribing physician sent a newer referral that switched her to dimethyl fumarate (Tecfidera, Biogen). The Walgreens Specialty pharmacist immediately called the physician to verify this switch in medication, which the physician verified. By April 18, the dimethyl fumarate was delivered and received by BT at her home.

On April 17, prior to receiving her MS DMT, BT received initial counseling from the Walgreens Specialty pharmacist to support her medication adherence and empower her MS self-care management. This counseling consisted of medication information regarding the administration of the starter dose, 120-mg capsules for 7 days with titration to the 240-mg maintenance dose. Storage, side effects, and pregnancy precautions were also relayed to BT. General information about MS and the importance of routine physician follow-up was also relayed, as well as any questions or concerns that she may have had at that time. Typical of many patients who are processing this new information, BT called back that afternoon with more questions about side effects. She was immediately transferred to a pharmacist to address her questions. These interactions became a strong foundation for an ongoing positive, supportive relationship with BT, who often expresses her satisfaction and appreciation for her Walgreens Specialty Pharmacy team.

The Walgreens specialty pharmacist called this patient on April 29 to support her with her DMT titration to the 240-mg dose. Adherence, side effects, and medication counseling were provided. BT had started her medication, was managing side effects, and had no concerns or further questions.

At the time of BT’s first refill reminder call on May 9, she had not missed any doses nor reported issues on side effects.

However, she requested counseling on taking her DMT and was transferred to the pharmacist by the pharmacy technician. At this time, she also expressed a need for copay assistance, and was immediately helped to apply for the copay card. BT received her copay card, and on May 20, her card information was documented for continued reference within the Walgreens Specialty Pharmacy system.

BT often expresses that she looks forward to her reminder calls, and regularly thanks her pharmacy technicians and pharmacists. She accepts the option to speak with a pharmacist about her medication, side effects, managing her MS symptoms, and any other concerns that she may have.

This case study shows the issues faced by many patients with MS and the importance of regular contact and intervention by a specialty pharmacist. Many patients, like BT, appreciate the ongoing support that this type of program provides them.

—K.L.

body can be affected, and symptoms can vary widely. The most common symptoms include numbness, balance and coordination problems, bowel and bladder dysfunction, vision problems, dizziness and vertigo, sexual dysfunction, pain, cognitive dysfunction, emotional changes, and spasticity.

Depression and fatigue also are common, and can interfere significantly with quality of life (QoL).4 There are 4 types, or courses, of progression: relapsingremitting, primary-progressive, secondary-progressive, and progressive-relapsing MS. Each course can be mild, moderate, or severe.

Most people (85%) initially are diagnosed with relapsing-remitting MS; during this course of the disease, they can experience a relapse or exacerbation of symptoms alternating with complete or partial remission during which no disease progression occurs.5 In the secondary-progressive course, the disease worsens steadily, with fewer or shorter periods of remission. Historically, about 50% of people diagnosed with the relapsing-remitting form developed secondary-progressive MS within 10 years. Long-term data are not yet available to determine whether the disease-modifying therapies (DMTs), which became available starting in the 1990s, significantly delay this transition.5

MS Therapy and Challenges Because there is no cure for MS, the goal of therapy is to decrease the scale of disability, slow progression of the disease, treat individual symptoms, and enable the highest QoL possible.

Management of patients with MS is multipronged and can include DMTs, corticosteroids to treat severe relapses, and symptom management with medications to address specific symptoms, such as depression, fatigue, cognitive issues, bowel and bladder problems, spasticity, pain, and so forth. Additionally, most patients with MS benefit from various forms of rehabilitation, such as physical therapy, occupational therapy, speech and swallowing therapy, cognitive rehabilitation, and vocational rehabilitation.

Approximately three-fourths of patients with MS find benefit in complementary therapies, such as acupuncture and biofeedback.6 Thirteen FDA-approved DMTs are considered primary therapy for MS: alemtuzumab (Lemtrada, Genzyme); dimethyl fumarate (Tecfidera, Biogen); interferon β (IFNβ)-1a (Avonex, Biogen;

13

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

Rebif, EMD Serono/Pfizer), IFNβ-1b (Betaseron, Bayer HealthCare; Extavia, Novartis), fingolimod (Gilenya, Novartis); glatiramer (Copaxone, Teva Neuroscience); glatiramer (Glatopa, Novartis); mitoxantrone (Novantrone, EMD Serono); natalizumab (Tysabri, Biogen); peginterferon β-1a (Plegridy, Biogen); and teriflunomide (Aubagio, Genzyme).

Of these, 7 are administered by injection, 3 are infused, and 3 are oral (Table).

These agents are effective for many patients.7 However, medication adherence is a major concern due to the complex administration of most of the agents (infusion and self-injection) and their debilitating side effects, namely, flu-like symptoms and headache.

In a multicenter study of patients with MS prescribed injectable DMTs, nonadherence rates (patients missing one or more injections) ranged from 36% to 39%.8 The most common reason for nonadherence was forgetting to administer the injection (58%).

Other reasons included injection-site

Myelin sheath

Normal

Damaged myelin

Multiple Sclerosis

reactions, diminished QoL, unfavorable perceptions of injectable medications, depression, and lack of support.

Although the move toward oral medications removes some of those factors, adherence issues are not completely resolved because patients may forget to take their medications, and side effects remain problematic.

Side effects such as fatigue and depression are major challenges in the management of patients with MS, and their effects are multifactorial. They are not only difficult for patients to handle, but they also can negatively affect medication adherence. Patients with MS have a 25% to 50% lifetime risk for developing depression,9 with symptoms ranging from a general state of sadness to decreased energy, and even thoughts of suicide. Patients with MS who have depression are more likely to have a worse prognosis and more rapid disease progression.10 More than 80% of individuals with see MANAGING MS, page 14

Table. Characteristics of Multiple Sclerosis Medications Drug

Indication

Dosage

Storage

Alemtuzumab (Lemtrada, Genzyme/Sanofi)

Relapsing forms of MS

2 infusions 1 y apart; initial: 12 mg/d for 5 d; second: 12 mg/d for 3 d

Refrigerate and protect from light. Do not freeze or shake.

Dimethyl fumarate (Tecfidera, Biogen)

Relapsing forms of MS

Twice daily, orally; starter dose: 120 mg for 7 d; maintenance dose: 240 mg ongoing

Store at room temperature and protect from light. Once opened, discard bottles after 90 d.

Fingolimod (Gilenya, Novartis)

Relapsing forms of MS

0.5 g orally daily

Store at room temperature.

Glatiramer (Copaxone, Teva)

Relapsing forms of MS

20 mg SQ daily OR 40 mg SQ 3 times/ wk

Refrigerate; may be stored at room temperature for up to 30 d.

Glatiramer (generic) (Glatopa, Novartis)

Relapsing forms of MS

20 mg SQ daily

Refrigerate; may be stored at room temperature for up to 30 d.

IFNβ-1a (Avonex, Biogen)

Relapsing forms of MS

30 mcg IM 1 time/wk

Refrigerate and protect from light. Vials may be stored at room temperature for up to 30 d, syringes for up to 7 d.

IFNβ-1a (Rebif, EMD Serono/Pfizer)

Relapsing forms of MS

22 or 44 mcg SQ 3 times/wk; titration required

Refrigerate and protect from light. Vials may be stored at room temperature for up to 30 d, syringes for up to 7 d.

IFNβ-1b (Betaseron, Bayer)

Relapsing forms of MS

250 mcg SQ every other day

Store at room temperature, but refrigerate after reconstitution and use within 3 h. Do not freeze.

IFNβ-1b (Extavia, Novartis)

Relapsing forms of MS

250 mcg SQ every other day

Store at room temperature, but refrigerate after reconstitution and use within 3 h. Do not freeze.

Natalizumab (Tysabri, Biogen)

Relapsing forms of MS

300 mg IV every 4 wk

Refrigerate and protect from light. After dilution, solution should be infused immediately. If not used immediately, refrigerate solution at 2°-8°C, and use within 8 h (warm to room temperature before administration). Do not freeze.

Mitoxantrone (Novantrone, EMD Serono)

Secondary-progressive MS, progressive-relapsing MS, worsening relapsing-remitting MS

12 mg/m2 IV every 3 mo (lifetime max: 140 mg/m2)

Store at room temperature. After penetration of the stopper, store remaining undiluted concentrate no longer than 7 d between 59° and 77°F or 14 d under refrigeration. Do not freeze.

Peginterferon β-1a (Plegridy, Biogen)

Relapsing forms of MS

SQ every 14 d; 1st starter dose: 63 mcg; 2nd starter dose: 94 mcg; maintenance dose: 125 mcg ongoing

Refrigerate; may be stored at or below 77°F for up to 30 d.

Teriflunomide (Aubagio, Genzyme/Sanofi)

Relapsing forms of MS

7 or 14 mg orally daily

Store at room temperature.

IFN, interferon; IM, intramuscular; MS, multiple e sclerosis; SQ, subcutaneous

14

Specialty Pharmacy Continuum • September/October 2015

CLINICAL

MANAGING MS continued from page 13

MS suffer from fatigue, and most say it is the worst symptom.11,12 Fatigue tends to worsen later in the day, and can significantly interfere with a patient’s ability to function at home and at work.

Fatigue may last less than a month to 6 months or longer.

Adherence Challenges in MS Therapy—Pharmacists Can Help Failure to use medications as directed has been described as the single greatest detractor to efficacy for many individuals with MS.19,20 Getting to the nugget of what is causing an individual’s nonadherence requires an honest reporting of missed doses and the realization of barriers causing him or her to miss taking his or her medication. Adherence barriers in MS are often listed as perceived lack of efficacy, forgetfulness, depression/cognitive impairment, side effects/adverse events, inconvenience, needle phobia, treatment fatigue, changed family or financial situation, complacency, and so forth. Multiple sclerosis nonadherence can affect all therapies prescribed for a typical MS multidisciplinary treatment plan, which may include exercise as well as physical, behavioral, cognitive, and complementary therapies. Adherence to the treatment plan is vital to maximize and maintain an individual’s wellness and QoL. To take this concept a step farther, studies comparing patient self-reporting data with medication adherence data that are collected through electronic dose monitoring have suggested that at least 80% of patients overestimate their adherence.17 Physicians and other health care providers also overestimate the degree to which their patients are taking the therapies they prescribe.18 Therefore, as clinicians, we need to be cognizant of these perceptions and the challenges they bring.

Pharmacists can assist in empowering patients to be adherent by listening to patients’ unique barriers and variances to successful adherence while encouraging them to continue taking their DMTs, as well as medication for MS symptom management. Offer support and information showing them research indicating that the single best strategy for delaying disease progression is adherence to their MS treatment plan.

Counseling patients so that they are well informed about the disease and the purpose of treatment also assists them in perceiving the need for a medication outweighs the inconvenience and possible side effects. Individuals living with MS have options to switch medications with the variety of therapies available today. Supporting them with the necessary medication information for a new

DMT empowers them, creating an even greater need to assist in balancing these new risks and benefits.

Walgreens Specialty Pharmacy Solutions Walgreens Specialty Pharmacy clinical support, counseling, and interventions are available for individuals with MS when they receive their DMTs from any Walgreens Specialty Pharmacy location. Through our Central Specialty fulfillment centers, the patient’s DMT is delivered to the patient’s home or sent directly to the physician’s office, and our pharmacists offer clinical support by telephone. Walgreens patients with MS can also choose to accept

Improved Outcomes, Lower Costs The goal of the Walgreens Connected Care MS program is to provide excellent patient care resulting in reduction or delay of disease progression, improved outcomes, enhanced QoL, and reduced health care costs. Close contact, as provided by Walgreens, is particularly important to help patients with MS understand the importance of taking their medications and to manage their not-inconsequential side effects.

The medication possession ratio of Walgreens-managed patients with MS is 94%,13 which is significantly higher than the 63% reported in one study of patients treated at 17 neurology clinics.8

macists’ ability to improve medication adherence and increase QoL for patients with MS.

References 1. National Multiple Sclerosis Society. Who gets MS? (Epidemiology). www.nationalmssociety. org/What-is-MS/Who-Gets-MS. Accessed May 15, 2015.

2. Edlin M, Sonnenreich P. Trends in managing multiple sclerosis. P T. 2008;33(10):611-614.

3. Ziemssen T. Multiple sclerosis beyond EDSS: depression and fatigue. J Neurol Sci. 2009;277(suppl 1):S37-S41.

4. National Multiple Sclerosis Society. What causes MS? www.nationalmssociety.org/ What-is-MS/What-Causes-MS. Accessed May 15, 2015.

5. National Multiple Sclerosis Society. Definition of MS. www.nationalmssociety.org/What-isMS/Definition-of-MS. Accessed May 15, 2015.

6. National Multiple Sclerosis Society. Complementary & alternative medicines. www. nationalmssociety.org/Treating-MS/Complementary-Alternative-Medicines. Accessed May 15, 2015.

7.

National Multiple Sclerosis Society. Treating MS. www.nationalmssociety.org/Treating-MS. Accessed May 15, 2015.

8. Treadaway K, Cutter G, Salter A, et al.

Factors that influence adherence with disease-modifying therapy in MS. J Neurol.

2009;256(4):568-576.

9. Chwastiak L, Ehde DM, Gibbons LE, et al.

Depressive symptoms and severity of illness in multiple sclerosis: epidemiologic study of a large community sample. Am J Psychiatry.

2002;159(11):1862-1868.

the offer of telephonic clinical support and intervention offerings when filling prescriptions at their most convenient retail location. This is a highly effective way to manage patients with conditions such as MS. This model provides an extra opportunity for pharmacy professionals to connect with patients, which can make all the difference for medication adherence, of which the variance to success is affected by ongoing DMT side effects and MS symptoms.

Walgreens Specialty Pharmacy employs an approach that promotes patients’ self-efficacy in the management of their MS. Each individual has his or her own unique experience when administering a specific DMT, as medication side effects and MS symptoms can change in type, intensity, and frequency along the continuum of the disease.

This patient-centric support is driven by patient responses to questions within scheduled assessments including depression, fatigue screenings, and counseling interventions. The patient’s physician is notified of positive screenings and symptoms or side effects that the patient is experiencing of which the physician may not be aware. Management of depression and fatigue in patients with MS is key to maintaining well-being and medication adherence.13 These interventions are the cornerstone of the Walgreens Connected Care MS program.

Specialty pharmacists play an important role in early identification of patients who may be suffering from depression and fatigue, and ensure that these issues are addressed by the patient’s physician. Research has shown that managed patients with MS whose depression symptoms were addressed are significantly more compliant in taking their MS medications than those whose depression was not managed: 86% versus 38%, respectively.2 Additionally, studies have shown that overall health care costs are lower for patients who are medication adherent compared with those who are not.14-15 Although research is limited regarding the relationship between adherence and cost of MS medications, preliminary Walgreens research has suggested that although drug costs are lower for patients who are noncompliant, medical costs are significantly higher, including costs for inpatient admissions and MSrelated medical service costs.16 Furthermore, patient nonadherence is costly from a health aspect, resulting in poorer health care status.

Conclusion Specialty pharmacists play a crucial role in the continuity of care for patients with MS. A system of pharmacy-provided support that includes regular contact, expert guidance, and excellent care is the cornerstone of specialty phar-

10. Joffe RT. Depression and multiple sclerosis: a potential way to understand the biology of major depressive illness. J Psychiatry Neurosci.

2005;30(1):9-10.

11. Zifko UA. Management of fatigue in patients with multiple sclerosis. Drugs.

2004;64(12):1295-1304.

12. Zifko UA. Therapy of day time fatigue in patients with multiple sclerosis [in German].

Wien Med Wochenschr. 2003;153(3-4):65-72.

13. Walgreens data on file.

14. Horne R. Compliance, adherence, and concordance: implications for asthma treatment.

Chest. 2006;130(1 suppl):S65-S72.

15. Bender BG, Rand C. Medication non-adherence and asthma treatment cost. Curr Opin Allergy Clin Immunol. 2004;4(3):191-195.

16. Khandelwal N, Jiang J, Moyer S, et al. Relationship between adherence to multiple sclerosis medications and total healthcare costs.

Presented at the International Society for Pharmacoeconomics and Outcomes Research 13th Annual International Meeting; Toronto, Ontario, Canada; May 3-7, 2008.

17. Zeller A, Ramseier E, Teagtmeyer A, et al.

Patient’s self-reported adherence to cardiovascular medication using electronic monitors as comparators. Hypertens Res. 2008;31(11):2037-2043.

18. Lugaresi A, Ziemssen T, Oreja-Guevara C, et al. Improving patient-physician dialog: commentary on the results of the MS Choices survey. Patient Prefer Adherence. 2012:143-152.

19. Costello K, Kennedy P, Scanzillo J. Recognizing nonadherence in patients with multiple sclerosis and maintaining treatment adherence in the long term. Medscape J Med. 2008;10(9):225.

20. Haynes RB, Yao X, Degani A, et al. Interventions to enhance medication adherence. Cochrane Database Syst Rev. 2005;(4):CD000011.

15

Specialty Pharmacy Continuum • September/October 2015

INDUSTRY NEWS

Avella Partners With Fertility Source

Specialty Pharmacies Selected To Distribute Gefitinib for Lung Ca

A

vella Specialty Pharmacy has partnered with Fertility SOURCE Companies, one of the largest egg donor and surrogacy organizations in the United States. As part of the partnership, Avella will provide significant discounts on specialty medications used in fertility procedures, including follitropin β (Follistim, Merck), chorionic gonadotropin (Pregnyl, Merck), menotropins injection (Menopur, Ferring), ganirelix acetate, progesterone and many others.

“Avella has been a provider of fertility medications since 1996,” said John Musil, PharmD, Avella’s founder and chairman of the board, in an interview with Specialty Pharmacy Continuum.

“Over time, the cost of surrogacy and egg donation has gone up significantly, with technological advances and more regulatory issues. The cost of having a baby via surrogate is well over $50,000.

Manufacturers have been wonderful in providing financial assistance, but we wanted to further help these patients.”

Although the partnership has just been launched and is still evolving, Dr. Musil said that patients receiving their fertility medications through the Avella-Fertility SOURCE partnership should expect a 10% to 15% reduction in the cost of the drugs.

Those discounts are “stackable” with manufacturer discounts, he added. “If we know the patient is receiving a 50% discount from Merck, for example, they’re still going to receive a discount from us.”

Jason Ott, PharmD, a clinical fertility specialist with Avella, said he is not aware of any other such coordinated, ongoing partnerships between a specialty pharmacy and donor and surrogacy programs. “There may have been some short-term partnerships on specific programs, but nothing ongoing,” he said. “Avella is proud to be able to help people pursuing fertility options by not only providing guidance and premier service, but also through access to more affordable medications.”

P

harmacy pay-for-performance is here to stay which in turn makes demonstrating healthcare delivery excellence more important than ever.

That’s why forward thinking pharmacy owners like Byron Yoshino of Pharmacare in Hawai’i have utilized The Compliance Team’s* Exemplary Provider® “EP” accreditation since 2007.

Today, The Compliance Team offers pharmacies a full line-up of Exemplary Providerbranded accreditation programs including ones for Specialty, Community, Infusion, Sterile & Non-sterile Compounding, LTC, DMEPOS and Retail Clinic.

A

straZeneca selected three specialty pharmacies—Avella, Biologics and Diplomat—to distribute gefitinib (Iressa), the lung cancer drug that recently returned to the U.S. market after a decade’s absence.

After being withdrawn from the market in 2005 because clinical trials in a general population failed to show a survival advantage, the drug’s new label gives specific guidance on the population eligible to receive it. Gefitinib was approved by for patients with metastatic non-small cell lung cancer whose tumors have epidermal growth factor receptor exon 19 deletions or exon 21 (L858R) substitution mutations. The drug is approved with the therascreen EGFR RGQ PCR Kit as a companion diagnostic.

“This is a very difficult cancer to treat, and gefitinib definitely fills a need for very specific patients,” said Avella’s Leslie Yendro, the vice president of business development, in an interview with Specialty Pharmacy Continuum. “In oncology, the biggest barrier to therapy in many cases is tolerating the treatment, and access to hterapy. We will be helping break down the financial barriers to access, making sure the drug is affordable, whether people are commercially insured, government insured or have no insurance at all. For many patients this will be their last, best option, and we don’t want them to have to go through a long wait.”

Each “EP” program includes at no extra cost: expert-led orientation webinars; plain language Safety-Honesty-Caring® quality standards; hundreds of accreditation related documents; and access to the industry’s oldest and largest patient satisfaction reporting and benchmarking database.

For more details about The Compliance Team’s industry leading value packed pharmacy accreditation programs call us at 215.654.9110 or visit our web site at www.TheComplianceTeam.org

Visit us in Orlando at

AMCP Nexus

Exemplary Provider Accreditation ®

October 26-29

*The Compliance Team is nationally recognized and Medicare approved to accredit Part A-Rural Health Clinics and all Part B-DMEPOS providers.

Byron Yoshino President/CEO Pharmacare Hawaii Infusion/Specialty and LTC Pharmacy DMEPOS

16

Specialty Pharmacy Continuum • September/October 2015

OPERATIONS & MANAGEMENT 1,400

COPAY HELP

1,217

1,200

continued from page 1

The Power of Copay Cards Copay cards are clearly driving utilization. “If there are three products for the same condition that have the same mechanism of action, the doctors are going to write the prescription for the one that has the better copay card,” Mr. Kus said. “Our medical group is smart

1,000

Dollars, $

917 826

800

735 616

600

5 584

400 200 0 2006

2007

2008

2009

2010

2011

2012

2013

2014

Figure 1. Average deductible for single coverage.

Source: Kaiser Family Foundation data; from Zitter Health Insights’ presentation.

‘Cost sharing is surpassing patients’ ability to pay. Real people can’t afford these drugs.’

—Mark Zitter

enough to always ask their patients if they can afford the drug and explain their out-of-pocket expense.”

When financial assistance isn’t available for one drug, prescribers will often switch to another. “We recently had a situation where one of the nonprofit sources of copay support for a leading prostate cancer drug ran out for 60 days. We saw an instant change in prescribing patterns, with physicians switching [to] the leading competitor drug. They’re trying to take care of their patients, so even if they believe one drug might be a little better, the fact is that the most expensive drug is the one that’s not taken.”

Such changes are understandable,

Copay nonutilizers

given the huge drug costs that patients would face in the absence of specialty pharmacy copay support programs.

According to Zitter Health Insights’ 2015 Co-Pay Offset Monitor report, the average out-of-pocket oncology drug cost for patients whose copay was covered by their insurance program was only $29; the balance of the copay, at $436, was covered via specialty copay support (Figure 2).

Copay assistance definitely drives patient adherence, said Mr. Zitter.

When Zitter Health Insights’ 2015 CoPay Offset Monitor asked rheumatoid arthritis patients on IV therapy, “How impactful is your copay program on your decision to refill your prescrip-

Copay covered by program for utilizers

None of the sources reported any relevant financial conflicts of interest.

Out-of-pocket program utilizers

29 12

Dollars, $

is surpassing patients’ ability to pay.

Real people can’t afford these drugs.”

In a recent assessment of 183 health plans, Mr. Zitter found that 38 of them—or 21%—required satisfying a deductible before the pharmacy copay even applies. Of those, 22 required patients to meet deductibles higher than $1,000. The average deductible for single coverage has nearly doubled in less than a decade, going from $584 to $1,217, according to the Kaiser Family Foundation (Figure 1), and deductibles of more than $1,000 are increasingly common—found in 41% of all firms in 2014, compared with just 10% in 2006. Even deductibles of $2,000 or more are no longer rare, found at 18% of all firms in 2014.

“We are accustomed to the idea of a $25 copay for a first-tier drug and a $50 copay for a second-tier drug, but that’s increasingly not true. People don’t have the copays they thought they had,” Mr. Zitter said.

What’s more, he said, the old threetier system has rapidly given way to a norm of four to six tiers. In Zitter Health Insights’ Fall 2014 Managed Care Biologics and Injectables Index, 56% of the 102 payors surveyed anticipated four to six tiers in their most representative formulary design used with specialty drugs and biologics for 2015. That number was just 33% in 2013. “We’ve also found that one in six benefit designs has no coinsurance maximum on tier 4,” Mr. Zitter said.

“There’s a lot of exposure, given the cost of these drugs. People are struggling a lot more, especially in January and February, when they’re trying to meet the deductible.”

Providers know that their patients are struggling, Mr. Zitter said. Of 208 rheumatologists surveyed by Zitter Health Insights, 58% said that their patients “sometimes” indicate that they can’t afford their medications, and 42% said that they “very often” do so. (Only a single physician answered “never” to the survey.)

All of this suggests that without copay assistance, much of specialty pharmacy would fall apart, with patients unable to afford their share of the cost of these medications. “If you didn’t have copay support, nonadherence would go wild,” Mr. Kus suggested.

1 135 1,135 1,097 991

tion?” the average response, on a scale from 1 to 5 with 5 being most influential, was 4.63. Patients taking less costly subcutaneous therapy still ranked copay assistance as fairly important, at 3.93 of 5 on average. Fifty percent of IV patients would ask to be switched to a cheaper alternative drug if their assistance program became unavailable.

Manufacturers clearly know this, and are competing at the copay coupon level, Mr. Kus said. “Your market share is a lot less if your competitor has a better copay card, especially in the specialty pharmacy arena. As you see more and more five-tier plans with 25% to 50% coinsurances, it’s essential that manufacturers’ copay plans are competitive.”

For many brands, copay support is the No. 1 marketing cost, Mr. Zitter noted.

“In the last few years, we’ve seen a number of manufacturers make the decision not to try to get second-tier status for certain products anymore, and instead apply those dollars to copay support programs,” he said.

As biosimilars enter the market over the next few years, those products will probably need to have copay assistance as well, noted Zitter Health Insights’ Jason Rucker, the product director of syndicated research, who came to the company from a copay card vendor in North Carolina.

“Their cost, while it’s expected to be less, won’t be as [low] as generics have been,” Mr. Rucker said. “There will still be a cost burden, and still a need for some type of copay assistance. As more and more products have biosimilar competition, you’re going to see that as the next boost to copay offset programs.”

—Gina Shaw

12 6 71

436

114 34

No. of claims

22

5,449

555

Oncology

54,707

167

48,970

Rheumatoid arthritis

45,103

370 20

14,885

Multiple sclerosis

5,344

730

Hepatitis C

Figure 2. Average out-of-pocket costs for program utilizers.a a

2014 Q3. Data based on average of 525,000 prescriptions processed quarterly through specialty pharmacies, representing 25% of national specialty pharmacy claims.

Source: Zitter Health Insights’ Co-Pay Offset Monitor.

151

56

33

2,122

1,165

Pulmonary arterial hypertension

17

Specialty Pharmacy Continuum • September/October 2015

OPERATIONS & MANAGEMENT

The Case for Accreditation: Why It Matters Obtaining an accreditation for specialty pharmacy proves to pharmaceutical companies, patients and others that the pharmacy can deliver quality care, which should make it an important aspect of the pharmacy’s business. tation preparedness with a person’s daily tasks and daily duties,” explained Danyell Jones, the senior vice president of marketing at BHM Healthcare Solutions in St. Louis, a consulting firm that

not understaand why accreditaation is a benefit to them,” hem ” said Ms. Jones, so you need to show them that accredited organizations have a competitive edge.

Involve staff in the process by having each department write the SOPs for that department. “First, they are the only ones who ultimately know what see ACCREDITATION, page 19

Unit Do s Bar Cod e, ing, Pharma Nursing cy & Supp Experts ly !

Medi-Dose/EPS labels are specifically designed for every need…from solids to liquids, syringes to ampules, IV lines and bags to insulin and suppositories. Plus, with our MILT® software, you can even add optional bar codes.

You name it. At Medi-Dose/EPS, there’s a label for that!

Scan to see these labels in action!

800.523.8966

M

Yet, many specialty pharmacies do not always give the process the attention it requires to be successful, said experts in specialty pharmacy accreditation.

Accreditation is more than just writing up a couple of standard operating procedures (SOPs), making sure everyone is on their best behavior while the surveyor is in the building and then ignoring the SOPs until it is time for reaccreditation. Accreditation should become part of the mindset of the operation, guiding the pharmacy toward excellence.

“There can be a misperception that the accreditation piece is separate from what they do day to day, when the reality is if they are really incorporating [the standards] into their practices, it becomes part of the day to day. It is not a separate thing,” said Sandra Canally, the founder and president of The Compliance Team in Spring House, Pa. Therefore, choose an accreditor who suits your needs and will enhance your pharmacy practices, Ms. Canally suggested.

There are differences in standards, processes, time, culture and costs.

Review the standards to make sure that you understand what they are, what they cover, how they are organized and the scope of what you have to do to meet them. “Make sure the standards match your practice and vision,” suggested Lynnae M. Mahaney, BSPharm, MBA, FASHP, the executive director at the Center for Pharmacy Practice Accreditation in Madison, Wis. “I look at accreditations a little like a partnership,” added Greg Stowell, the education and consulting manager at Accreditation Commission for Health Care in Orlando, Fla. “Yes, our survey assesses an organization based on its compliance with a set of relevent standards that are good and appropriate, but ultimately, it is a partnership. If the pharmacy does not buy into our requirements, then I would argue that they are probably with the wrong accreditor.”

Mr. Stowell said he was surprised at the number of pharmacies that do not research the accreditor thoroughly before choosing one. It is important to determine the subtle differences among them to find the best fit for the pharmacy.

Preparation for an accreditation can take anywhere from six months to a year, depending on the SOPs at the pharmacy. It is critical that the specialty pharmacy gives itself enough time to write them. “If you wait until the last minute, it is difficult to juggle accredi-

provides assistance to organizations seeking accreditation from accredited bodies, such as URAC in Washington, D.C. Take advantage of the preparation tools provided by the accreditor, too.

Make sure that everyone in the company is on board with the accreditation, they said. That buy-in—not only from the rank and file, but also from the top—is essential to be successful.

“Sometimes the financial people might

MediDose.com

18

Specialty Pharmacy Continuum • September/October 2015

OPERATIONS & MANAGEMENT

Ambulatory Pharmacies Move Into Specialty With HCV As increasing numbers of hospitals and health systems open their own on-site ambulatory pharmacies, specialty pharmacies may soon face more competition for significant segments of their market—with hepatitis C virus (HCV) topping the list of therapeutic categories used as a point of entry.

When St. Vincent Hospital, a 285-bed acute care hospital in Worcester, Mass., prepared to open its own on-site ambulatory pharmacy, one of the facility’s

biggest proponents on the medical staff was infectious disease specialist George Abraham, MD, MPH, the hospital’s associate chief of medicine.

Dr. Abraham operates a busy practice, Primary Physician Partners, with a hospital-based office that was literally around the corner from the new ambulatory pharmacy, which opened in July 2013. Over the following year, as new curative HCV drugs, such as Gilead’s sofosbuvir (Sovaldi) and ledipasvir (Harvoni), entered the market, Dr. Abraham’s practice began treating his patients using these medications—

Not a subscriber yet?

Here’s what you’re missing: • In-depth meeting coverage of specialty pharmacy conferences • Disease State Spotlights on oral chemotherapy, HCV, orphan drugs and other disorders treated with leading specialty pharmacy medications.

• Policy updates on 340B, biosimilars, accreditation, cold chain requirements, and more.

• Practice Profiles of innovative specialty pharmacy operations.

To begin your FREE subscription, scan the QR code below or visit us at: www.specialtypharmacycontinuum. com/Subscription

And welcome to Specialty Pharmacy Continuum!

and the pharmacy thought it only made sense that it should fill many of these prescriptions, rather than an off-site specialty pharmacy.

“Because several significant health plans in Massachusetts have open networks, any pharmacy could fill specialty prescriptions for many of these patients, and so we were able to offer the convenience of filling their prescriptions right around the corner from their doctor’s office,” said Jason Poquette, RPh, the director of outpatient pharmacy services at St. Vincent. The pharmacy has been filling HCV prescriptions for only about six months, but Mr. Poquette said their volume is already averaging six to seven new patients monthly.

AmerisourceBergen and its national specialty pharmacy, US Bioservices, have been providing guidance and partnerships for several hospitals and health systems aiming to capture some of the HCV revenue—or at a minimum, to provide better provider and patient satisfaction by aligning with one specialty pharmacy partner. “Beginning in 2012, we started seeing a lot of interest from health systems in this area,” said Erin Rausch, the vice president for specialty client strategies at AmerisourceBergen.

“We’re now working with several health systems in various stages of implementing specialty solutions. Each one has been customized because each one wants something a little different.”

With St. Vincent, for example, they helped the in-house pharmacy establish a system of its own. US Bioservices also provides “wraparound” services on an a la carte basis, offering a “bridge” solution to health systems as they develop their own specialty pharmacy infrastructure, with benefits verification services, 24-hour call center, patient assistance and copay support, and patient clinical management and monitoring.

“AmerisourceBergen focuses on assisting health systems interested in getting into the specialty space by providing them with a short-term and longterm glide path to optimizing their HCV and overall specialty capture rate as quickly as possible,” Ms. Rausch added.

“Regardless of the model, hepatitis C has very good margins, so they tend to focus on that disease state to start with if they’re looking to establish a specialty pharmacy contract partnership,” she stressed.

Depending on the level of 340B involvement, hospitals can expect anywhere from a 5% to 10% capture rate during the first year of initiating an HCV specialty program in their pharmacies, she added. “By two years out, they can be up around a 25% to 30% capture rate.

That, of course, is highly contingent on what infrastructure is in place to coordi-

19

Specialty Pharmacy Continuum • September/October 2015

OPERATIONS & MANAGEMENT

Web Only Partnering With An Established Specialty Provider Hospitals venturing into specialty might be seen as a threat by some specialty pharmacy providers, but to others, it’s an opportunity. About four years ago, Diplomat Pharmacy Inc. started to extend its existing support services program for retail pharmacies into the hospital space. For more details on these partnerships, scan the adjacent QR code or visit www. specialtypharmacycontinuum.com/ DiplomatRetail.

nate and hand-hold prescriptions from the providers into the pharmacy.”

St. Vincent’s pharmacy now has three options for filling its HCV prescriptions: The patient can pick up directly from the pharmacy, pharmacy staff can deliver it directly to the physician’s office or the prescription can be shipped directly to the patient.

“Most patients choose to pick up their medications from the doctor’s office, where they get an additional counseling opportunity,” Mr. Poquette said.

“Then we take an approach of trying to hit them midway through the 28-day therapy cycle, checking in with a 14-day midcycle call so the patient is getting frequent reminders and adherence

counseling, which is so critical. We also call the doctor’s office prior to the next visit to coordinate the filling of medication with the next visit.”

Steady Growth Mercy Fitzgerald Hospital in Darby, Pa., has operated its ambulatory pharmacy in partnership with AmerisourceBergen/Pharmacy Healthcare Solutions since 2012. Kevin Bisch, PharmD, the hospital’s director of outpatient pharmacy, said they began exploring the possibility of providing HCV prescriptions

for local physicians in November 2014.

Since then, HCV prescriptions filled through the pharmacy have climbed to a rate of about 10 new patients per month.

“Our primary infectious disease specialist likes the patient to be present in the office with their prescription when they initiate therapy, so the doctor can review the side effects and the importance of taking medication as scheduled and completing therapy,” Dr. Bisch said.

“With the pharmacy on campus, the patient can stop here on their way to the doctor’s office and have a one-on-one,

in-person consultation.”

Both Dr. Bisch and Mr. Poquette said, in just the short time they’ve been filling prescriptions for HCV medications, there has been a noticeable change to the bottom line. “It’s fair to say that this endeavor alone has doubled our monthly revenue for the outpatient pharmacy,” Mr. Poquette noted.

—Gina Shaw The sources reported no relevant financial conflicts of interest apart from employment by their respective companies.

in Your Inbox ... to receive the monthly e-newsletter from

at www.specialtypharmacycontinuum.com

ACCREDITATION continued from page 17

the pharmacy does, so who better to help in the development process than those that perform the tasks,” Mr. Stowell said. “On the other side of the coin, staff involvement also creates buy-in, which is critical for successfully achieving accreditation.”

Hiring a consulting firm to help during the accreditation process is fine, they said, but the pharmacy still needs to put in the hours and the “sweat equity” to get the most out of the accreditation.

They can be a helpful resource because they know the accrediting agencies and understand the standards.

“Accreditation helps align you on the path of measurement and monitoring that helps your pharmacy succeed. It forces you to look at your processes,” Ms. Canally said. Writing your own SOPs, or starting with a template that you can customize, and making sure that every department is involved will help ensure that accreditation is part of the corporate culture, she noted.

—Marie Rosenthal The sources reported no relevent financial conflicts of interest apart from employment by their respective companies.

Get the latest news delivered directly to your computer and PDA. The interactive format has embedded website links that give you instant access to additional information as well as unique searching features and printing capabilities.

Each installment contains brief summaries of the most important articles from the current month’s issue, and breaking news ahead of print.

Register for free @ www.specialtypharmacycontinuum.com

20

Specialty Pharmacy Continuum • September/October 2015

POLICY

340B MEGA-RULE continued from page 1

of the most complicated programs that pharmacists must manage.

To add clarity to the rules, HRSA, which oversees the program, recently issued its proposed 340B Drug Pricing Program Omnibus Guidance that most agree does clarify many, but not all, issues. However, it is not without controversy, so experts expect quite a few comments before the final guidance comes out sometime next year. The comment period ends Oct. 27, 2015.

“It has been a long time coming,” said Randy Barrett, of 340B Health, in a statement that the organization issued shortly after the document was released.

“There are gray areas in the program, and we look forward to having more clarity. This is an important process, and it is our hope that safety-net health care providers will not find themselves limited in their ability to meet their mission to treat the underserved.”

Who Is a 340B Patient?

One of the most controversial areas might be the updated definition of an eligible patient. “I think all participants, pharmacies, covered entities and even manufacturers have struggled to understand some of the requirements and procedures, specifically concerning who is [an eligible] patient,” said Matt Sneller, PharmD, the vice president of pharmacy affairs at Talyst, which provides 340B third-party administrator services to covered entities and contract pharmacies. “It has always been difficult to understand the definition of when is a patient not a patient and what is the true definition of a covered outpatient drug.”

There are now six criteria that narrow the definition of an eligible patient as opposed to three (box).

“Previous guidance issued in the mid-1990s adopted a three-part test for whether or not an individual is considered a patient who is eligible to receive drugs purchased at 340B prices. The mega-guidance offers a more detailed and nuanced six-part test to determine eligibility,” said John Arnold, JD, an attorney with the law firm Waller, headquartered in Nashville, Tenn. “The new definition of a patient will exclude patients from 340B status if, for example, their care was provided by an organization that is an affiliate of the covered entity, such that the covered entity is not itself billing for the services. And it would exclude, for example, discharge medications and patients who received

care from providers who only had privileges at the covered entity and are not an employee or independent contractor of the covered entity.”

One area that will probably cause consternation is that “the individual’s drug must be prescribed or ordered pursuant to an outpatient service,” noted Joseph W. Metro, JD, a partner at the law firm of Reed Smith, in Washington, D.C. Hospital pharmacists have been implementing drug adherence programs, hoping to minimize 30-day readmissions. Because the prescription typically is filled by the outpatient pharmacy in such cases (hospital owned or contracted), and is done for a patient whose status had changed to outpatient, safety-net providers thought these prescriptions qualified for 340B pricing.

The new guidance would say they do not, according to Mr. Metro.

“The fact that someone has received an inpatient service and leaves the hospital with a prescription, even though that prescription is being filled on an outpatient basis at a retail pharmacy,

the prescription for the infusion comes into play, Mr. Metro said.

“The mere administration does not count,” he stressed. “You must be treating the patient for the underlying condition.”

This could be a hardship, especially for rural facilities, Mr. Sneller noted. In the past, he said, a patient could travel to a regional cancer center several miles

Who Is a 340B Patient?

The Health Resources and Services Administration has expanded the criteria for an individual to be eligible for 340B drugs: 1. The individual receives a health care service at a facility or clinic site, which is registered for the 340B program and listed on the public 340B database.

2. The individual receives a health care service provided by a covered entity provider who is either employed by the covered entity or is an independent contractor for the covered entity, such that the covered entity may bill for services on behalf of the provider.

3. An individual receives a drug that is ordered or prescribed by the covered entity provider as a result of the service described in the second criterion.

4. The individual’s health care is consistent with the scope of the federal grant, project designation or contract.

5. The individual’s drug is ordered or prescribed pursuant to a health care service that is classified as outpatient.

6. The individual’s patient records can be accessed by the covered entity and demonstrate that the covered entity is responsible for care.

would not be sufficient [to garner 340B status],” Mr. Metro explained. “This guidance suggests that … inpatients are not eligible under the 340B program.”

Another area that will cause concern, especially for specialty pharmacies and cancer infusion centers, is patient ineligibility for 340B pricing if the only health care received was an infusion. These providers will have to show that the patient is receiving treatment for cancer or other condition in an outpatient setting of a safety-net health care provider before

Your Comments Needed!

Read the proposed 340B mega-guidance. This is not a final rule and the Health Resources and Services Administration is soliciting comments at www.regulations.gov/#!home. The comment period ends Oct. 27, 2015.

from home to see an oncologist, who would provide a prescription for the patient to receive the infusion at his or her local hospital or specialty pharmacy.

“Those drugs used with that infusion were all 340B eligible. Now, they are saying they are not because the patient was not seen by a physician at the covered entity,” he said. “Even though the facilities are providing all the medical services that are required with that infusion, that is no longer sufficient. This will be very financially burdensome to all covered entities.”

This guidance does not appear to recognize the amount of medical care that “goes with infusing that drug,” he added, including nursing and pharmacy care.

Another point of contention is who

provides the outpatient services. Under the mega-guidance, the safety-net health care provider must be the entity billing for the outpatient service. This would be a specialty or outpatient pharmacist or physician who is employed by the safety-net health care provider or who has a contract with that provider, rather than a practice that is affiliated with the hospital but does its own billing.

“So this would exempt patients who receive care from providers who only had privileges at the covered entity, and they are not employees or independent contractors of the covered entity,” explained Mr. Arnold, meaning “there is a connection and a direct line between the health care service and the ordering of a prescription drug.”

This rule seems to encourage an area of the program that has been criticized (most recently in a Government Accountability Office report on the program) for inducing hospitals to purchase more private practices, especially community cancer centers, to qualify for more 340B discounts.

“The guidance will require affiliations between providers and hospitals to be tighter, either employer–employee types of relationships or under-contract types of relationships, rather than affiliations,” Mr. Metro said. He added that this requirement probably won’t affect large teaching or regional facilities with many different types of employee relationships, but could have a greater effect on smaller, rural hospitals and centers.

Although this guidance does provide clarity for many issues, it is still subject to public comment, Mr. Metro reiterated, so some facilities might be wondering how to handle 340B products before the final rule is released. Some covered entities, which will bear the brunt of increased audits, may begin implementing provisions of the new guidance now, he noted. Others will say it is just a draft, so they should wait.

—Marie Rosenthal The sources reported no relevant financial conflicts of interest.

21

Specialty Pharmacy Continuum • September/October 2015

POLICY

BIOSIMILARS continued from page 1

with each other in their attempts to balance patient safety concerns, competing industry interests and the impetus to cut drug costs.

According to CMS’s proposed rule, all biosimilars of a reference product would receive one Health Care Common Procedure Coding System (HCPCS) code and, for Part B reimbursement, hospital outpatient providers would initially be reimbursed 106% of the manufacturer’s wholesale acquisition cost. Once manufacturers calculate an average sales price (ASP), reimbursement will change to 100% of the biosimilars’ ASP and 6% of the ASP of the reference product. (For the Fact Sheet, go to the CMS website at https:// goo.gl/jL6riI.) Whether the reference product and the biosimilars are ultimately coded together or separately, costs will likely fall, according to Bonnie Kirschenbaum, MS, FASHP, who is an expert on reimbursement issues.

“If the reference product keeps its own unique code and the entire biosimilar pool shares another, pricing and sales competition between the biosimilars will drive the ASP down,” Ms. Kirschenbaum said. “And if there is just one HCPCS code for both the reference product and its biosimilars, sales will likely sway toward biosimilars and reimbursement for the reference prod-

and Innovation Act of 2009, which states biosimilars should be reimbursed separately and have unique payment rates and unique HCPCS codes.

“CMS is treating biosimilars like they’re generic drugs, which they’re not,” said Mr. Werner. “Not only do biosimilars follow a completely different FDA approval pathway, but they also could

‘If the CMS rule is approved as is, it is likely to reduce all biosimilar options for patients.’

—Michael Werner

“I don’t understand the logic behind having four random letters,” said Scott Soefje, PharmD, the president of the Hematology/ Oncology Pharmacy Association (HOPA).

“It could be confusing for prescribers. Most of us would prefer an easier way to identify a company.”

Dr. Soefje said using a suffix could also be problematic from a health information technology perspective.

“Some older EMRs [electronic medical records] have a character limit in the drug name field that could cut off the full suffix,” noted Dr. Soefje, who is also the director of pharmacy at the University Medical Center Brackenridge, in Austin, Texas. “So, from a list, the prescriber may not be able to distinguish the innovator product from the biosimilar. The HOPA Biosimilar Task Force believes a prefix would avoid this problem.”

What’s To Come?

‘I don’t understand the logic behind having four random letters.’

submitted comments to CMS indicating as much.

Unique Identifiers Urged

—Scott Soefje, PharmD

uct will get dragged down. The reference product would then lower its purchase price and the ASP for the entire pool drops, too.”

The potential result of downward pressure on pricing has the Biosimilars Forum, a nonprofit organization including 11 drug manufacturers, “gravely concerned” (www.biosimilarsforum.org/news/ biosimilars-forumexpresses-concern-cms-proposedrule-biosimilar-payment).

“If the CMS rule is approved as is, it is likely to reduce all biosimilar options for patients,” said Michael Werner, a partner at Holland & Knight LLP, in Washington, D.C., and a policy advisor for the Biosimilars Forum. “That would be a real economic disincentive for manufacturers to invest in biosimilars.”

The Biosimilars Forum argued that the proposed CMS rule is out of line with the Biologics Price Competition

have different indications even if they are tied to the same reference product.”

The CMS proposed rule also sparked a reaction from Congress. In a letter dated Aug. 4, 33 members of Congress expressed “serious concern” that the proposed rule does not recognize a difference between biosimilars and smallmolecule generics, and it said the signatories believed a “vibrant biosimilars market” requires that each biosimilar receive a unique HCPCS code (http:// goo.gl/nfoiNQ). The letter was spearheaded by Reps. Anna Eshoo (D-Calif.) and Joe Barton (R-Texas), both of whom have received significant campaign funding from the pharmaceutical industry (www.open-secrets.com).

The American Society of Health-System Pharmacists also opposed the CMS proposed rule, saying in an email that it prefers that CMS not apply these reimbursement regulations and that it has

Meanwhile, the FDA articulated that it believed not all biologics and biosimilars are necessarily created equal.

In a draft guidance issued in August, the agency suggested creating specific prescribing names for each biosimilar (http://goo.gl/RRrBe5). “There is a need to clearly identify biological products to improve pharmacovigilance, and, for the purposes of safe use, to clearly differentiate among biological products that have not been determined to be interchangeable,” the draft guidance stated.

The guidance suggested a reference biologic be prescribed by its chemical name alone, and that each biosimilar receive a unique suffix added to the chemical name. The suffix would consist of four random letters. So, a hypothetical biological product named transizumab would be prescribed as “transizumab” for the reference product, whereas a biosimilar version (made by Sandoz, for example), might be written as “transizumab-rndm,” instead of a more manufacturer-specific “transizumab-sndz,” for example.

The final CMS rule and FDA guidance are expected later this year. Both Dr. Soefje and Ms. Kirschenbaum said that, in some cases, the clinical distinction between biosimilars and their reference products could eventually disappear, since many products may prove interchangeable in safety and efficacy.

“Many of the biosimilars are products that Big Pharma has brought to market in other countries and they have been used successfully for many years, so the arguments that there are ‘unproven unknowns’ in some cases fall flat,” said Ms. Kirschenbaum.

Dr. Soefje echoed these thoughts, saying concern about clinical differences between biosimilars and reference products are hypothetical at the moment.

“I think that in five to 10 years, the biosimilars will be proven to be as effective and safe as their reference drugs,” he speculated.

—David Wild Mr. Werner reported serving as a policy advisor to the Biosimilars Forum, a nonprofit organization of 11 pharmaceutical companies. Ms. Kirschenbaum and Dr. Soefje reported no relevent financial conflicts of interest.

22

Specialty Pharmacy Continuum • September/October 2015

TECHNOLOGY

The Internet of Things

Linking Caregivers to Patients The Internet of Things (IoT) could transform health care by integrating more real-time data into decisions affecting patient care, the medication supply chain and regulatory compliance.

The IoT describes a process wherein a wide range of everyday objects, such as refrigerators and scales, can be connected to the Internet, allowing them to send and receive data.

Once health care professionals and patients master data emanating from billions of devices, the IoT could improve patient outcomes, speed care, streamline workflows and secure the supply chain, said Bill G. Felkey, MS, a professor emeritus of Healthcare InformaticsPharmacy Care Systems at the Auburn University James Harrison School of Pharmacy, in Alabama.

Mr. Felkey stressed that for IoT to work optimally in a health-system setting and beyond, its inherent limitations need to be appreciated. Specifically, pharmacists will need to “embrace learning machines and polling devices that show trends and issue real-time alerts, and understand which data require them to act and which not to reflexively react to, because devices won’t replace overt behavior by pharmacists,” he said.

As for what types of devices may be in play, he noted that the technology extends beyond the sophisticated data-emitting ones currently used in many hospital and specialty pharmacies, to include preadmission and postdischarge devices, such as vial caps and mobile apps that track compliance with medication regimens, blood glucose monitors and wearables that monitor heart rate and oxygen saturation.

Health care data obtained from such

devices could complete the care continuum and “finally achieve our goal to have fully engaged patients participating as members of their multidisciplinary care teams,” Mr. Felkey said.

A Wide Range of Devices At the recent Biosimilars 20/20 Conference in Philadelphia, Stanley Campbell, the chairman and CEO of EagleForce Associates and EagleForce Health, in Herndon, Va., offered his own vision for what the IoT may ultimately bring to health care. He discussed devices, such as scales, that could report sudden weight gains in heart failure patients and smartphone apps that could securely connect to patients’ electronic medical records to help patients and physicians better manage chronic conditions.

His company, which provides evidence-based clinical insight and business intelligence, is working on secure devices that use IoT technology. Mr. Campbell stressed that security, especially concerning health information, will be key if these devices are going to be accepted.

Specialty Pharmacy Applications The IoT isn’t just a glimpse of the future, however; evidence is beginning to accumulate that smartphone apps can be a powerful tool for promoting medication compliance post-discharge. A study presented at the 2015 Armada Specialty Pharmacy Summit revealed a significant improvement in

medication adherence amon ng patients with HIV who useed a mobile app developed by mscripts, m in San Francisco, for refill rreminders, dosage reminders and otherr prescription information.

Patients who did not usee the app were 2.9 times more likely to di discontinue their medication regimens than patients who used the app, reported Eric Sredzinski, PharmD, the executive vice president of clinical affairs and quality assurance for Avella Specialty Pharmacy, in Scottsdale, Ariz. He noted that 79% of Avella patients using the app achieved 90% or greater adherence, compared with 65.3% of patients who did not use the platform.

The study used proportion of days covered to assess adherence rates in HIV patients who were taking single and multiple-source medications, including efavirenz-emtricitabine-tenofovir (Atripla, Bristol-Myers Squibb) and emtricitabine-tenofovir (Truvada, Gilead).

“The No. 1 reason for not being adherent is forgetfulness,” Dr. Sredzinski said in an interview with Specialty Pharmacy Continuum. “Having a tool that can provide reminders about your refills as well as when to take your medication provides an extra support system. Most of us are pretty well tethered to our cell phones, so having something that is always around has the ability to change patients’ behavior.”

Let the (IT) Buyer Beware Regardless of the vendor one chooses as a partner, data obtained from mobile health apps and other digital sources produce a liability burden that some pharmacists and caregivers do

not want, Mr. Felkey noted. “One could legally argue that a caregiver ignored data points if he or she didn’t act on them. Thus, some say ‘don’t give it to me,’” he explained.

“Others say, ‘give me all of it, sorted to the most relevant points and customized to the individual patient.’ Still others want only data that require action, such as a CHF [congestive heart failure] patient who gained 10 pounds of heart-related edema.”

These mixed approaches will make the IoT more or less robust in different care settings, as each decides its stance on the basis of culture and developing literature, Mr. Felkey said.

—Al Heller The sources reported no relevant financial conflicts of interest.

Web Only A Willingness To Embrace IoT Stakeholders seem ready to embrace the Internet of Things (IoT), according to a survey by Forrester Consulting. For more details, scan the adjacent QR code or visit specialtypharmacycontinuum.com/IoTSurvey.

Interested in Best Practices in automation, informatics and patient safety?

Then don’t miss our next issue of PTR, mailing in March 2016.

To request a free subscription to PTR, send email to BWilson@McMahonmed.com, with PTR Subscription in the subject line.

Scan the adjacent QR code for a direct email link.

Read Specialty Pharmacy Continuum Anywhere, Anytime!

Download the iPad App here.

Š 2015 Amgen Inc. All rights reserved.

Not for reproduction or distribution. USA-145-104559