Specialty Drug Approvals: 2015 Highlights + 2016 Projections by Diplomat

Specialty Drug Approvals 2015 HIGHLIGHTS + 2016 PROJECTIONS

c l i n i c a l s e rv i c e s

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DRUG APPROVAL TRENDS* 1,2,3,4,5 FDA approvals have increased in recent years: • 45 novel new drug approvals in 2015 + 9 biologics (as of Dec. 30, 2015) • 41 novel new drug approvals in 2014 + 19 biologics • 25 novel new drug approvals per year on average from 2005 to 2013

Of the 54 new drug and biologic approvals in 2015: • Approximately half are considered specialty pharmacy–dispensed products • Many new drugs received special FDA designations, such as breakthrough, fast track, orphan, accelerated approval and priority review, on their way to approval

Disease states with the greatest number of approvals in 2015: • Rare diseases (25) • Oncology (13)

*Numbers include novel drug approvals only. Expanded indications for previously approved drugs, new formulations, generics, biosimilars, and intravenously administered oncology products are excluded.

IN 2015, the FDA tied the record for the most novel new drug approvals in a year since the creation of the Prescription Drug User Fee Act (PDUFA). Special FDA designations—such as breakthrough, fast track, orphan, accelerated approval and priority review—apply to promising drugs or those that treat diseases with an unmet medical need. These designations have reduced the time needed for clinical trials and/ or reduced the FDA review timeline, allowing pipeline products to come to market more quickly than in the past.6 Once again, specialty drug products accounted for a sizable portion

(approximately half) of the total new drugs and biologics approved by the FDA this year. Similar to 2014, rare diseases and oncology saw the most newly approved drugs in the specialty pharmacy market. In 2015, 25 rare disease and 13 oncology products were approved, with some drugs counting as both rare disease and oncology approvals. 2,3, 4

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RARE DISEASES8 In the past, rare diseases were sometimes viewed by manufacturers as less attractive targets for product development. Due to low patient populations, it was perhaps understandable to think the utilization of a new orphan drug product would be low and therefore profits would be low as well. That thinking has changed in recent times; treating rare diseases is now often considered an appealing opportunity. Orphan diseases often have little to no treatment competition for a particular condition. These products are typically high-cost, allowing for potentially high earnings even if there are few patients who may benefit. Manufacturers earn a period of market exclusivity after FDA approval is granted for a rare disease product, receive certain tax incentives and may have access to certain funding for drug development.5

Additionally, manufacturers developing an orphan product that treats either a pediatric disease or a neglected tropical disease have the opportunity to earn a priority review voucher. The voucher is redeemable with the FDA for a future priority review for any pipeline product the manufacturer requests, and the owner also has the option to sell it. These vouchers have become valuable assets. In fact, one voucher was sold for $350 million over the summer.7 The number of pipeline orphan drug products has greatly increased in recent years, with a high of 293 agents gaining orphan designation in 2014 (see next page). Prior to 2003, there were never more than 95 products earning orphan designation in a particular year.8

Oncology continues to have an active pipeline. Key approvals in the oncology field for 2015 include Ibrance® (palbociclib) for estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative breast cancer; Tagrisso™ (osimertinib) for non–small cell lung cancer in patients with T790 genetic mutation; Farydak® (panobinostat) and Ninlaro® (ixazomib), each for multiple myeloma, and Lonsurf® (trifluridine and tipiracil) for colorectal

cancer. Also worth noting, Zarxio™ (filgrastimsndz) became the first biosimilar approved in the U.S. It is a biosimilar of Neupogen® (filgrastim). Zarxio™ is approved for all except one of the same indications as Neupogen®, but the FDA does not allow the biosimilar to be used interchangeably with the name-brand product.

YEAR

Number of Orphan Designations Granted by the FDA8

2010

195

2011

203

2012

190

2013

260

2014

293

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ONCOLOGY9

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HEPATITIS C9 Chronic hepatitis C (CHC), perhaps more than any other disease state, has seen the treatment landscape change dramatically over the last two to three years. In 2015, we saw some additional approvals and expanded indications to treat some of the less common forms of the disease in the United States. Daklinza™ (daclatasvir) was approved for genotype 3 and Technivie™ (ombitasvir + paritaprevir + ritonavir) earned

an indication for treating genotype 4. Harvoni® (ledipasvir + sofosbuvir) gained expanded indications, covering HIV/CHC coinfection in patients with CHC genotypes 1, 4, 5 and 6; genotype 1 treatment-naïve cirrhotics; and CHC genotypes 4, 5 and 6 regardless of treatment experience or cirrhosis status.

In early 2015, we saw the arrival of Cosentyx® (secukinumab) for psoriasis. It became the first drug targeting interleukin (IL)-17A to earn FDA approval. Other agents with this mechanism of action are currently in the late-stage pipeline as well. Also of note was the approval of Glatopa™ (glatiramer acetate), the first generic of Copaxone®. Glatiramer acetate is a complex

molecule that proved to be more difficult for generic manufacturers to develop than the average small-molecule drug, but it is not a biosimilar.

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IMMUNOLOGY AND MULTIPLE SCLEROSIS9

10 2015 SPECIALTY APPROVALS

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Approval Date

Drug

Indication

2,3

Route

Approximate Population (U.S.)

Q1 2015 1/21/15

Cosentyx® (secukinumab)

Psoriasis

SubQ

7.5 million

1/23/15

Natpara® (parathyroid hormone)

Hypoparathyroidism

SubQ

60,000

1/29/15

Imbruvica®* (ibrutinib)

Waldenstrom’s macroglobulinemia

Oral

1,000 to 1,500 diagnoses/year

2/3/15

Ibrance® (palbociclib)

Breast cancer (ER+, HER2-)

Oral

1 million

2/13/15

Lenvima® (lenvatinib)

Thyroid cancer

Oral

600,000

2/18/15

Revlimid®* (lenalidomide)

Newly diagnosed multiple myeloma

Oral

60,000

2/23/15

Farydak® (panobinostat)

Multiple myeloma

Oral

90,000

3/6/15

Zarxio™ (filgrastim-sndz)

Biosimilar Neupogen® for neutropenia

SubQ and IV

60,000 diagnoses per year

3/17/15

Cholbam™ (cholic acid)

Bile acid disorders

Oral

<10 in 1 million

4/16/15

Glatopa™ (glatiramer acetate)

Multiple sclerosis

SubQ

400,000

4/29/15

Ixinity® (recombinant factor IX)

Hemophilia B

3,400

Q3 2015 7/2/15

Orkambi™ (lumacaftor + ivacaftor)

Cystic fibrosis

Oral

25,000

7/10/15

Envarsus® XR (tacrolimus extendedrelease tablets)

Kidney transplant rejection

Oral

<200,000

7/11/15

Rapamune®* (sirolimus)

Lymphangioleiomyomatosis

Oral

30,000 to 50,000 worldwide

7/13/15

Iressa® (gefitinib)

Non–small cell lung cancer

Oral

400,000 all NSCLC

7/24/15

Praluent® (alirocumab)

Hypercholesterolemia

SubQ

625,000

7/24/15

Odomzo® (sonidegib)

Basal cell carcinoma

Oral

2.8 million diagnoses/ year

*Expanded indication [Does not include IV or other health care provider–administered oncology products]

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Q2 2015

Diplomat Clinical Services | Specialty Drug Approvals

12 7/24/15

Daklinza™ (daclatasvir)

Hepatitis C, genotype 3

Oral

10% of HCV population in the US

7/24/15

Technivie™ (ombitasvir + paritaprevir + ritonavir)

Hepatitis C, genotype 4

Oral

1% of HCV population in the US

8/7/15

Keveyis™ (dichlorphenamide)

Periodic paralysis

Oral

5000

8/27/15

Repatha™ (evolocumab)

Hypercholesterolemia

SubQ

625,000

9/4/15

Xuriden™ (uridine triacetate)

Hereditary orotic aciduria

Oral

20 world wide

9/11/15

Humira®* (adalimumab)

Hidradenitis suppurativa

SubQ

155,000

9/15/15

Nuwiq® (simoctocog alfa)

Hemophilia A

16,500

9/22/15

Lonsurf® (trifluridine + tipiracil)

Colorectal cancer

Oral

1.1 million

Q4 2015 10/20/15

Coagadex® (coagulation factor X)

Hereditary factor X deficiency

300-600

10/23/15

Strensiq™ (asfotase alfa)

Hypophosphatasia

SubQ

1 in 100,000

11/4/15

Nucala® (mepolizumab)

SubQ

Not well understood; 10–20% of all asthma patients have poorly controlled symptoms

Eosinophilic asthma

11/5/15

Genvoya® (elvitegravir + cobicistat + HIV emtricitabine + tenofovir alafenamide)

Oral

1.1 million

11/10/15

Cotellic™ (cobimetinib)

Melanoma (in combination with Zelboraf)

Oral

920,000

11/12/15

Harvoni * (ledipasvir + sofosbuvir)

HIV/HCV coinfection with genotypes 1, 4, 5 and 6; genotype 1 treatment naïve cirrhotics; and HCV genotypes Oral 4, 5 and 6 regardless of treatment experience or cirrhosis status

Genotypes 4, 5 and 6: 3% combined of the HCV population in the U.S. 25% of HIV patients are coinfected with HCV

11/13/15

Tagrisso™ (osimertinib)

Non–small cell lung cancer

Oral

3,000 with this particular genetic mutation (T790)

11/13/15

Adynovate® (Factor VIII)

Hemophilia A

16,500

11/20/15

Ninlaro® (ixazomib)

Multiple myeloma

Oral

60,000

12/8/15

Vonvendi™ (von Willebrand factor)

Von Willebrand disease

Up to 1 in 100, no definitive diagnostic test

12/8/15

Kanuma™ (sebelipase alfa)

Lysosomal acid lipase deficiency

1 in 525,000

12/11/15

Alecensa® (alectinib)

Non–small cell lung cancer

Oral

400,000 all NSCLC

12/22/15

Uptravi® (selexipag)

Pulmonary arterial hypertension

Oral

15–50 cases in 1 million

*Expanded indication [Does not include IV or other health care provider–administered oncology products]

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IN THE PIPELINE The specialty drug pipeline continues to be strong, with a variety of novel products for new indications in development. Some trends are expected to continue into 2016 and beyond, with several approvals expected in the areas of rare diseases and oncology. Biosimilars will continue to be in the news as manufacturers try to bring them to the market. However, brand name manufacturers are expected to continue to fight the launch of biosimilar products in court. Some potentially high-volume biosimilars, for products such as adalimumab (Humira®) and etanercept (Enbrel®), have already filed with the FDA for review. The courts will be busy with legal arguments from both sides regarding biosimilars.

The cost of drugs—and the sustainability of payors and patients to cover their expenses—is expected to continue to be a major issue going forward. Discussions about what can be done to improve the health care system in terms of drug access and cost are sure to continue in 2016 and for a long time thereafter. In terms of specific drug approvals anticipated in 2016, particularly interesting products include: • Obeticholic acid for primary biliary cirrhosis (and later, non-alcoholic steatohepatitis)9 • Alectinib and brigatinib for non–small cell lung cancer in patients with ALK genetic mutation9 • Velpatasvir, a new hepatitis C agent paired with Sovaldi® (sofosbuvir) that has the potential to treat all genotypes9

2016 Expected Specialty Approvals9 Expected FDA Decision Date

Drug

Target Indication

Route

Population (U.S.)

Early Q1 2016

Drisapersen

Duchenne muscular dystrophy

SubQ

1–2 in 10,000

Early 2016

N9-GP/NN-7999

Hemophilia B

3,400

Daclizumab

Multiple sclerosis

SubQ

400,000

HIV

Injection

1.1 million

Cystic fibrosis additional gene mutation (NonG551D gating)

Oral

25,000 entire CF population; NonG551D mutation about 2% of this

Hemophilia B

3,400

Anemia

SubQ and IV

35–40% of cancer patients

Hepatitis C, genotypes 1, 4 and 6

Oral

Genotype 1: 70%; Genotypes 4 and 6: 2% combined

Duchenne muscular dystrophy

1–2 in 10,000 males

First-line treatment for CLL

Oral

16,000 new diagnoses yearly

Early 2016 Possibly Q1 2016

Possibly Q1 2016

Possibly Q1 2016 Possibly Q1 2016 1/28/16 2/26/16 3/15/16

Remune™

(HIV-1 immunogen) Kalydeco®*

(ivacaftor) Factor IX + recombinant albumin Epoetin alfa biosimilar Grazoprevir + elbasvir Eteplirsen Imbruvica®*

(ibrutinib)

3/31/16

Reslizumab

Eosinophilic asthma

Not well understood; 10– 20% of all asthma patients have poorly controlled symptoms

3/31/16

Defibrotide

Veno-occlusive disease of the liver

Oral

1–5 in 10,000

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Q1 2016

Q2 2016

16 Daklinza®

(daclatasvir) + Sovaldi®* (sofosbuvir)

Diplomat Clinical Services | Specialty Drug Approvals

4/6/16

Mycapssa™

4/15/16

(octreotide) Xalkori®*

4/15/16

(crizotinib)

HCV/HIV coinfection, HCV with advanced cirrhosis, and posttransplant HCV recurrence

Oral

25% of HIV patients are coinfected with HCV; posttransplant recurrence: 1/3 of transplant patients

Acromegaly

Oral

20,000

Non–small cell lung cancer with ROS1 mutation

Oral

1% of NSCLC patients have ROS1 mutation

4/30/16

Ixekizumab

Psoriasis

SubQ

7.5 million

5/29/16

Obeticholic acid

Primary biliary cirrhosis

Oral

40 in 100,000

Gilotrif®*

Lung squamous cell carcinoma

Oral

25–30% of lung cancers

Non–small cell lung cancer with T790 mutation

Oral

3,000 with this particular genetic mutation (T790)

Lambert-Eaton myasthenic syndrome

Oral

2–3 in 1 million

Non–small cell lung cancer

Oral

400,000 (all NSCLC)

6/25/16

(afatinib) Rociletinib

6/28/16

Firdapse® Possibly Q2 2016

(amiphampridine phosphate)

Possibly Q2 2016

Brigatinib Etanercept

Possibly Q2 2016

(Enbrel® biosimilar made by Sandoz)

Same as Enbrel®

SubQ

Same as Enbrel®

Possibly Q2 2016

Deutetrabenazine

Huntington’s disease

Oral

30,000

Possibly Q2 2016

Cabozantinib*

Renal cell carcinoma

Oral

17,000 for second line or later RCC

Velpatasvir +

Hepatitis C, pangenotypic

Oral

4.4 million

Possibly Q2 2016

Sovaldi®

*Expanded indication [Does not include IV or other health care provider–administered oncology products]

Diplomat Clinical Services | Specialty Drug Approvals

MIKE | DIPLOMAT PHARMACIST

2015 Key Approvals

Cosentyx® Ibrance® Praluent® Repatha™ Tagrisso™

20 22 24 26 28

Diplomat Clinical Services | Specialty Drug Approvals

Cosentyx® (secukinumab)10 Psoriasis

Diplomat Clinical Services | Specialty Drug Approvals

INDICATION Treatment of adult patients with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. CLINICAL TRIAL BRIEFING Secukinumab was evaluated for the treatment of psoriasis in four multicenter, randomized, double-blind, placebo-controlled trials composed of a total of 2403 patients. Patients enrolled in the studies received either 150 or 300 mg of secukinumab, placebo, or in certain studies, a biologic active control. Dosing was completed on weeks zero, one, two, three and four, and every four weeks thereafter. For certain studies, patients receiving placebo who were nonresponders were crossed over and received secukinumab weekly during weeks 12 to 16, and then every four weeks thereafter. Two studies were 12 weeks in duration and two were 52 weeks in length. For all studies, the primary endpoint was the proportion of patients achieving a ≥75 percent reduction in Psoriasis Area Severity Index (PASI) at week 12 compared to baseline and a rating of clear or almost clear on the Investigator’s Global Assessment (IGA). Secondary endpoints included proportion of patients achieving ≥90 percent PASI at week 12 compared to baseline, maintenance of efficacy at week 52, and improvement in itching, pain and scaling at week 12 based on Psoriasis Symptom Diary. Across all four trials, PASI 75 ranged from, 67–71 percent for patients given 150 mg of secukinumab, 75–87 percent for patients given 300 mg of secukinumab, and 0–5 percent for patients given placebo. IGA of clear or almost clear was achieved by 51–53 percent of patients given 150 mg of secukinumab, 62–73 percent of patients given 300 mg of secukinumab, and 0–3 percent of patients given placebo. Proprietary information of Diplomat Pharmacy Inc. Subject to change without notice. Copyright © 2015 by Diplomat Pharmacy Inc. All rights reserved.

APPROVAL DATE: Jan. 21, 2015 MANUFACTURER: Novartis Pharmaceuticals CLASS: Interleukin-17A antagonist STORAGE: 2°C to 8°C (36°F to 46°F); protect from light HOW SUPPLIED: 150 mg/mL solution in a prefilled pen or syringe or a single-use vial containing 150 mg of lyophilized powder for reconstitution

Administer 300 mg by subcutaneous injection at weeks zero, one, two, three and four, then every four weeks thereafter. SAFETY Common Adverse Events: Nasopharyngitis, diarrhea and upper respiratory tract infection Serious Adverse Events: Infections, tuberculosis, Crohn’s disease exacerbations and hypersensitivity reactions OTHER AGENTS IN THERAPEUTIC AREA • Cimzia® (certolizumab pegol) • Enbrel® (etanercept) • Humira® (adalimumab ) • Otezla® (apremilast) • Remicade® (infliximab) • Simponi® (golimumab) • Stelara® (ustekinumab)

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DOSING

Ibrance® (palbociclib)11 Oncology

Diplomat Clinical Services | Specialty Drug Approvals

INDICATION Treatment of postmenopausal women with estrogen receptor (ER)–positive, human epidermal growth factor receptor 2 (HER2)–negative advanced metastatic breast cancer. Palbociclib is used in combination with letrozole. CLINICAL TRIAL BRIEFING Palbociclib was evaluated for the treatment of breast cancer in a randomized, open-label, multicenter study composed of 165 patients with ER-positive, HER2 negative advanced breast cancer who had not previously received systemic treatment. Patients on study received palbociclib plus letrozole or letrozole alone. Palbociclib was administered daily for 21 consecutive days, followed by seven days off. Dosing continued with this cycle until disease progression, unmanageable toxicity or consent withdrawal occurred. The primary endpoint of the study was progression-free survival (PFS) as measured by the Response Evaluation Criteria in Solid Tumors (RECIST). Additionally, overall response rate (ORR) was determined. Median PFS was 20.2 months for the palbociclib-plusletrozole group (95 percent CI: 13.8, 27.5) and 10.2 months for the letrozole-only group (95 percent CI: 5.7, 12.6). ORR was 55.4 percent for the palbociclib-plusletrozole group and 39.4 percent for the letrozole-only group. Overall survival (OS) was not available at the time of analysis. Approval was granted under the FDA accelerated approval program.

APPROVAL DATE: Feb. 3, 2015 MANUFACTURER: Pfizer Inc. CLASS: Kinase inhibitor STORAGE: 20°C to 25°C (68°F to 77°F); excursions permitted from 15°C to 30°C (59°F to 86°F) HOW SUPPLIED: 75, 100, and 125 mg capsules

Administer 125 mg of palbociclib orally once daily with food for 21 consecutive days followed by seven days off for repeated 28-day cycles. Take in combination with 2.5 mg of letrozole dosed once daily continuously for 28 days during the cycles. Doses of palbociclib may be reduced if adverse events occur. See prescribing information for details. SAFETY Common Adverse Events: Neutropenia, leukopenia, fatigue, anemia, upper respiratory infection, nausea, stomatitis, alopecia, diarrhea, thrombocytopenia, decreased appetite, vomiting, asthenia, peripheral neuropathy and epistaxis Serious Adverse Events: Neutropenia and infections

OTHER AGENTS IN THERAPEUTIC AREA • Afinitor® (everolimus)

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DOSING

PraluentÂŽ (alirocumab)12 Hypercholesterolemia

Diplomat Clinical Services | Specialty Drug Approvals

INDICATION Treatment as an adjunct to diet and maximally tolerated statin therapy for adult patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease, who require additional lowering of lowdensity lipoprotein cholesterol (LDL-C). CLINICAL TRIAL BRIEFING Alirocumab was evaluated in five multicenter, double-blind, placebo-controlled trials composed of 3,499 total patients. Patients on study had HeFH and/or clinical atherosclerotic cardiovascular disease and were receiving a maximally tolerated dose of a statin. Some patients were also receiving other lipid-modifying therapies. For three studies, the initial dose was 75 mg given every two weeks. If insufficient response in LDL-C was observed at week eight, dosing was increased to 150 mg every two weeks for week 12 and beyond. In the other two studies, only the 150 mg dose was administered. Selected patients received placebo in all studies. All studies were 52 weeks or greater in duration. The primary endpoint in all studies was mean percent change from baseline in LDL-C at week 24. Across the five trials, the mean treatment differences in LDL-C between alirocumab and placebo ranged from -36 percent (95 percent CI: -49, -24; p<0.0001) to -58 percent (95 percent CI: -61, -56; p<0.0001). Additional analyses related to the reduction of cholesterol and apolipoprotein were also performed.

APPROVAL DATE: July 24, 2015 MANUFACTURER: Sanofi-Aventis and Regeneron CLASS: PCSK9 inhibitor STORAGE: 36°F to 46°F (2°C to 8°C) HOW SUPPLIED: 75 and 150 mg/mL pens and syringes PATIENT POPULATION: HeFH - 1 in 500; clinical atherosclerotic cardiovascular disease, over 25 million patients in the U.S.

Administer subcutaneously once every two weeks. The recommended starting dose is 75 mg. Dosing may be increased to a maximum of 150 mg if LDL-C response is insufficient at the initial dose level. SAFETY Common Adverse Events: Nasopharyngitis, injection site reactions and influenza Serious Adverse Events: Hypersensitivity reactions OTHER AGENTS IN THERAPEUTIC AREA • Repatha™ (evolocumab)

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DOSING

Repathaâ&#x201E;˘ (evolocumab)13 Hypercholesterolemia

Diplomat Clinical Services | Specialty Drug Approvals

INDICATION Treatment as an adjunct to diet and maximally tolerated statin therapy for adult patients with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (CVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C). Additionally indicated for homozygous familial hypercholesterolemia (HoFH) when used in combination with other LDLlowering therapies. CLINICAL TRIAL BRIEFING Evolocumab was evaluated in four multicenter, double-blind, randomized, placebo-controlled trials composed of 813 total patients. Patients on study had hypercholesterolemia, including CVD with primary hyperlipidemia, HeFH or HoFH. Patients received statins and/or other lipid-modifying therapies in addition to evolocumab or placebo. Evolocumab was given 140 mg every two weeks or 420 mg monthly for 12 weeks in three of the trials and 52 weeks in the other trial. The primary endpoint of the studies was mean difference from placebo in LDL-C. Across the four trials, the mean treatment differences in LDL-C between evolocumab and placebo ranged from -31 percent (95 percent CI: -44, -18) to -71 percent (95 percent CI: -81, -61). Additional analyses related to the reduction of cholesterol and apolipoprotein were also performed.

APPROVAL DATE: Aug. 27, 2015 MANUFACTURER: Amgen CLASS: PCSK9 inhibitor STORAGE: 36°F to 46°F (2°C to 8°C). May be stored at room temperature for up to 30 days. HOW SUPPLIED: 140 mg/mL prefilled pens and syringes PATIENT POPULATION: HeFH: 1 in 500; HoFH: 1 in 1 million; clinical atherosclerotic cardiovascular disease: over 25 million in the U.S.

Administer by subcutaneous injection. For primary hyperlipidemia with CVD or HeFH: 140 mg every two weeks or once monthly, given as three consecutive 140 mg injections. For HoFH: 420 mg once monthly. SAFETY Common Adverse Events: Nasopharyngitis, upper respiratory tract infection, influenza, back pain and injection site reactions Serious Adverse Events: Allergic reactions OTHER AGENTS IN THERAPEUTIC AREA • Praluent® (alirocumab)

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DOSING

Tagrisso™ (osimertinib)14 Oncology

Diplomat Clinical Services | Specialty Drug Approvals

INDICATION Treatment of metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non–small cell lung cancer (NSCLC) in patients who have progressed on or after EGFR TKI therapy. CLINICAL TRIAL BRIEFING Osimertinib was evaluated for the treatment of T790M mutation-positive NSCLC in two multicenter, single-arm, open-label trials composed of 411 total patients. Patients on study had progressed on a prior EGFR TKI treatment and received 80 mg of osimertinib once daily. The primary endpoint of both studies was objective response rate (ORR) according to RECIST criteria as evaluated by a blinded independent central review. Additionally, duration of response (DUR) was measured. The ORR for the combined studies was 59 percent (95 percent CI: 54, 64). Fifty-nine percent of responses were classified as partial and 0.5 percent were complete responses. DUR ranged from 1.1 to 5.6 months after a median duration of follow-up for 4.0 months in one study and 4.2 months in the other.

APPROVAL DATE: Nov. 13, 2015 MANUFACTURER: AstraZeneca CLASS: Kinase inhibitor STORAGE: 25°C (77°F) with excursions permitted from 15°C to 30°C (59°F to 86°F) HOW SUPPLIED: 40 and 80 mg tablets PATIENT POPULATION: Approximately 60 percent of patients treated with an EGFR inhibitor develop T790M mutation

Administer 80 mg orally once daily, with or without food. SAFETY Common Adverse Events: Diarrhea, rash, dry skin and nail toxicity Serious Adverse Events: Interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy and embryo-fetal toxicity OTHER AGENTS IN THERAPEUTIC AREA • Gilotrif® (afatinib) • Iressa® (gefitinib) • Tarceva® (erlotinib)

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DOSING

About the Author

Diplomat Clinical Services | Specialty Drug Approvals

RYAN CHANDANAIS, LEAD AUTHOR Ryan Chandanais is an emerging therapeutics analyst at Diplomat in Flint, Michigan. His job is to gather, analyze and present pipeline intelligence involving specialty drug products. He has additional drug developmentâ&#x20AC;&#x201C;related experience at a contract research organization for pre-clinical drug studies, where he served as a research associate and report coordinator. He has earned a Master of Science in Integrative Pharmacology from Michigan State University and a Bachelor of Science in Education from Central Michigan University. He has acquired certifications as a pharmacy technician (CPhT) from the Pharmacy Technician Certification Board, and as a laboratory animal technologist (LATG) from the American Association for Laboratory Animal Science. He can be contacted at rchandanais@diplomat.is.

REFERENCES: 1. U.S. Food and Drug Administration Center for Drug Evaluation and Research. “Novel New Drugs 2014 Summary” January 2015. 2. U.S. Food and Drug Administration Website. “New Molecular Entity and New Therapeutic Biological Product Approvals for 2015” http://www.fda.gov/Drugs/DevelopmentApprovalProcess/DrugInnovation/ucm430302.htm (accessed December 8, 2015). 3. U.S. Food and Drug Administration Website. “2015 Biological License Application Approvals” http://www.fda.gov/ BiologicsBloodVaccines/DevelopmentApprovalProcess/BiologicalApprovalsbyYear/ucm434961.htm (accessed December 8, 2015). 4. U.S. Food and Drug Administration Website. “Search Orphan Drug Designations and Approvals” http://www.accessdata. fda.gov/scripts/opdlisting/oopd/OOPD_Results_2.cfm?Index_Number=309410 (accessed December 9, 2015). 5. Fast track, accelerated approval and priority review. Food and Drug Administration Website. http://www.fda.gov/ forpatients/approvals/fast/ucm20041766.htm (accessed December 8, 2015). 6. Developing products for rare disease & conditions. U.S. Food and Drug Administration (FDA) Website. http://www.fda. gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ucm2005525.htm (accessed December 1, 2015). 7. Priorityreviewvoucher.org. http://priorityreviewvoucher.org (accessed December 8, 2015). 8. FDA Law Blog – Hyman, Phelps, and McNamara, P.C. http://www.fdalawblog.net/fda_law_blog_hyman_phelps/orphandrugs (accessed December 4, 2015). 9. BioPharm Insight. Boston, MA: Infinata; 2013. http://www.infinata.com/biopharma-solution/by-product/biopharm-insight. html (accessed December 2015). http://www.fda.gov/ForIndustry/DevelopingProductsforRareDiseasesConditions/ ucm2005525.htm (accessed December 1, 2015). 10. Cosentyx® [package insert]. East Hanover, NJ: Novartis; 2015. 11. Ibrance® [package insert]. New York, NY: Pfizer; 2015. 12. Praluent® [package insert]. Bridgewater, NJ: Sanofi-Aventis U.S.; 2015. 13. Repatha™ [package insert]. Thousand Oaks, CA: Amgen; 2015. 14. Tagrisso™ [package insert]. Wilmington, DE: AstraZeneca; 2015.

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