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2016 HIGHLIGHTS & 2017 PROJECTIONS

Diplomat Clinical Services | Specialty Drug Approvals

Specialty Drug Approvals

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This document contains forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Forward-looking statements give current expectations or forecasts of future events or our future financial or operating performance. The forward-looking statements contained in this document are based on management’s good-faith belief and reasonable judgment based on current information, and these statements are qualified by important risks and uncertainties, many of which are beyond our control, that could cause our actual results to differ materially from those forecasted or indicated by such forward-looking statements. These risks include the number of patients prescribed such drug(s) currently and in the future, patient’s adherence to such drug(s), the number of distributors on panel and our relative distribution share, the timing of drug sales, the cost of such drug(s) and reimbursement rates by payors, drug competition, and the factors set forth in “Risk Factors” in Diplomat’s Annual Report on Form 10-K for the year ended Dec. 31, 2015, and in subsequent reports filed with or furnished to the Securities and Exchange Commission. Except as may be required by any applicable law, Diplomat assumes no obligation to publicly update such forward-looking statements, which are made as of the date hereof or the earlier date specified herein, whether as a result of new information, future developments, or otherwise. Certain information in this presentation concerning our industry and the markets in which we operate is derived from publicly available information released by third-party sources, including independent industry and research organizations, and management estimates. Management estimates are derived from publicly available information released by independent industry and research analysts and other third-party sources, as well as data from our internal research, and are based on assumptions made by us upon reviewing such data and our knowledge of such industry and markets, which we believe to be reasonable. We believe the data from these third-party sources is reliable. In addition, projections, assumptions, and estimates of the future performance of the industry in which we operate and our future performance are necessarily subject to uncertainty and risk due to a variety of factors, as discussed in Diplomat’s reports filed with the Securities and Exchange Commission. These and other factors could cause results to differ materially from those expressed in the estimates made by these third-party sources.


AT D I P L O M AT, we blend clinical excellence with a personal touch — for happier lives and health that lasts.


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DRUG APPROVAL TRENDS1,2,3,4,5 The number of novel new drugs approved by the FDA in 2016 declined substantially compared to each of the previous two years. Approval numbers are closer to average yearly totals from 2005–2013. Novel New Drug Approvals by Year* Year

Number of Novel New Drug Approvals

2016

22

2015

45

2014

41

2005–2013

25 (average per year)

Of the 22 novel new drug approvals in 2016: • Approximately half are considered specialty drugs, depending on the criteria used to define specialty products. This is a similar proportion as last year. • Eighteen (82%) received a special FDA designation (i.e. Breakthrough, Fast Track, Orphan, Accelerated Approval, Priority Review) on their way to approval.

Additionally, seven new biologics have been approved in 2016** for a total of 29 combined novel new drug and biologic approvals. The 2016 new approvals included a mix of oncology, immunology, rare diseases, and other disease states.

*Numbers from FDA webpage: Novel Drug Approvals for 2016. Includes novel new drug approvals only. Expanded indications, non-novel drug approvals, and new formulations or combinations are not included. **Numbers from FDA webpage: Biological License Application Approvals. Nonbranded biologics are not included.


INTRODUCTION1,2,3,5 Less than half the number of novel new drugs was approved in 2016 as in 2015. The total was similar to but still below the average number of approvals in each year from 2005 to 2013. It is also worth noting that approximately 17 specialty drugs also earned expanded indications. There might be a perception that fewer novel new drug approvals signifies

slowed growth in the specialty market, but this number does not speak to the impact of the drugs that were approved. Although the quantity was down in 2016, some important new drugs became available in each of the broad disease states covered by specialty pharmacy.

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RARE DISEASES4,5,6,7,8,9 Once again, rare diseases accounted for a large share of the new approvals in 2016. Nine of the 29 (31%) newly approved drugs have earned Orphan designation from the FDA, meaning they treat a patient population of less than 200,000 in the U.S. This continues to be an area of emphasis in drug development. Many rare diseases have no available treatments, so new drugs are often particularly significant to these patients. Exondys 51™ (eteplirsen) became the first drug in the U.S. to be approved for the treatment of Duchenne muscular dystrophy (DMD), but the decision to allow the drug to enter the marketplace was not agreed upon by all experts involved. Eteplirsen failed to meet the primary endpoint goal in pivotal studies, and the advisory committee panel voted that the drug did not sufficiently demonstrate efficacy. However, after a lengthy review process, the FDA decided to grant approval in September. Ocaliva® (obeticholic acid)

became the first drug approved to treat primary biliary cholangitis (PBC), a rare liver disease. Ocaliva® remains on the drug pipeline radar, as it continues to be evaluated for an expanded indication covering the treatment of nonalcoholic steatohepatitis (NASH), a disease with a much larger patient population that also lacks an FDA-approved treatment. Additionally, Defitelio® (defibrotide sodium) became the first treatment for hepatic veno-occlusive disease (VOD), another rare liver condition. VOD can occur in certain patients who receive chemotherapy and hematopoietic stem cell transplant. Eteplirsen and obeticholic acid were approved under the FDA’s Accelerated Approval program, which allows a drug to reach the market based on the results of a surrogate endpoint used in trials, but also requires additional post-marketing clinical trials to be performed to verify safety and efficacy in order to maintain permanent approval.


ONCOLOGY1,2,10 Venclexta™ (venetoclax) and Rubraca™ (rucaparib) were the only two orally dosed oncology products that qualified as novel new drug approvals in 2016. This is a surprisingly low number, given the overall high level of activity in the oncology pipeline. Along with venetoclax and rucaparib, there were two IV-administered agents launched this past year: Lartruvo™ (olaratumumab), for certain types of soft tissue sarcoma, and Tecentriq® (atezolizumab), an immuno-oncology agent for urothelial carcinoma. Additionally, diagnostic imaging agents Axumin® and Netspot™ were approved for the identification of prostate cancer and neuroendocrine tumors. These also met the FDA criteria for novel new agents. While the number of new approvals was low in oncology for 2016, if we dig a bit deeper, we find there were 15 instances of an oncology agent gaining approval for an

expanded indication, new dose formulation, new combination, or coverage of an expanded age group. While new drug approvals might be exciting, expanding the scope of currently approved agents is also an important avenue for reaching additional patients. Immunooncology continued to gain momentum, with Opdivo® (nivolumab) acquiring expanded indications to cover Hodgkin lymphoma and certain head and neck cancers. Keytruda® (pembrolizumab) earned the FDA’s OK for certain patients with non-small-cell lung cancer expressing PD-L1 in a first-line setting and also for head and neck cancers. The success of these immuno-oncology agents does not necessarily translate to high fill rates at most specialty pharmacies due to their IV route of administration.

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HEPATITIS C11,12 Given the remarkable advancements in hepatitis C virus (HCV) treatments in recent years, it’s becoming increasingly difficult to create a groundbreaking drug in this space. However, Epclusa® (sofosbuvir and velpatasvir) became the first pangenotypic treatment, meaning it is effective across all genotypes of the virus. Epclusa® is indicated for patients with or without cirrhosis, including both compensated and decompensated cirrhosis, although patients with decompensated

cirrhosis should add ribavirin to the treatment regimen. Additionally, Zepatier™ (elbasvir and grazoprevir) earned approval for treating genotypes 1 and 4. About three quarters of hepatitis C patients in the U.S. have genotype 1, so approval for this genotype covers the bulk of patients in the U.S. Zepatier™ demonstrated comparable safety and efficacy to similar previously approved treatments and was priced significantly lower, making it an attractive option for some payors.


IMMUNOLOGY AND MULTIPLE SCLEROSIS13,14,15,16,17 Two novel new drugs were approved for autoimmune diseases in 2016—one for psoriasis and another for multiple sclerosis (MS). Taltz® (ixekizumab) is an IL-17 inhibitor that became available in March for the treatment of moderate-to-severe plaque psoriasis. It’s the second drug with that mechanism of action to be approved for this disease state. Zinbryta™ (daclizumab) entered the market for relapsing forms of MS. It is an IL-2 inhibitor generally used after patients have had an inadequate response to two or more other MS treatments. Additionally, 2016 saw the approval of three

biosimilars: Inflectra® (infliximab-dyyb), Erelzi™ (etanercept-szzs), and Amjevita™ (adalimumabatto). These are biosimilars of Remicade®, Enbrel®, and Humira®, respectively. Although the products were approved by the FDA, patent law disputes have put a hold on the product launches for Erelzi™ and Amjevita™. Inflectra® also experienced a delayed launch after acquiring FDA approval in April; the product did not become available for distribution until December.

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2016 SPECIALTY APPROVALS2,3 (DOES NOT INCLUDE IV ONCOLOGY PRODUCTS)

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Approval Date

Drug

Manufacturer

Indication

Route

Approximate Population (U.S.)

SubQ

PSA: 1.5 million; AS: 700,000 to 900,000

Q1 2016

Diplomat Clinical Services | Specialty Drug Approvals

1/15/16

Cosentyx® (secukinumab)* Novartis

Psoriatic arthritis (PSA) and ankylosing spondylitis (AS)

Genotype 1: 70–75% of HCV in the U.S.

1/28/16

Zepatier™ (grazoprevir and Merck elbasvir)

Hepatitis C virus (HCV), genotypes 1 and 4

2/3/16

Ibrance® (palbociclib)*

Pfizer

Breast cancer, HR+, HER2(new combination with Oral Faslodex® [fulvestrant])

1 million

2/5/16

Daklinza® (daclatasvir)*

Bristol-Myers Squibb, Gilead

Hepatitis C, with HIV coinfection, advanced cirrhosis, and post– liver transplant HCV reoccurence

Oral

1/4 of HIV patients are coinfected with HCV; post-transplant recurrence in 1/3 of transplant patients

2/12/16

Harvoni® (ledipasvir and sofosbuvir)*

Gilead

Hepatitis C, specific patients with advanced liver disease

Oral

150,000 (specific patients with advanced liver disease)

2/26/16

Afinitor® (everolimus)*

Novartis

Gastrointestinal or lung neuroendocrine tumors

Oral

<16,000

3/1/16

Odefsey® (emtricitabine, rilpivirine, and tenofovir alafenamide)

Gilead

HIV

Oral

1.1 million

3/4/16

Idelvion® (coagulation factor IX [recombinant], albumin fusion protein)

CSL Behring

Hemophilia B

IV

3,400

3/4/16

Imbruvica® (ibrutinib)*

AbbVie

1st-line treatment of chronic lymphocytic leukemia (CLL)

Oral

115,000 (CLL total patients)

3/11/16

Xalkori® (crizotinib)*

Pfizer

Non-small-cell lung cancer (NSCLC), ROS1+

Oral

4,000 (NSCLC, ROS1+ genetic mutation)

*Expanded Indication

Oral

Genotype 4: 1% of HCV in the U.S.


Kovaltry® (antihemophilic factor [recombinant])

Bayer

Hemophilia A

IV

16,500

3/22/16

Taltz® (ixekizumab)

Eli Lilly

Psoriasis

SubQ

7.5 million

3/23/16

Cinqair® (reslizumab)

Teva

Severe asthma

IV

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

3/30/16

Defitelio® (defibrotide sodium)

Jazz

Hepatic veno-occlusive disease

IV

<160,000

Q2 2016 4/4/16

Descovy® (emtricitabine and tenofovir alafenamide)

Gilead

HIV

Oral

1.1 million

4/5/16

Inflectra™ (infliximabdyyb)

Celltrion

Multiple indications (Remicade® biosimilar)

IV

Several million

4/11/16

Venclexta™ (venetoclax)

AbbVie

Chronic lymphocytic leukemia (CLL) with 17p deletion

Oral

115,000

4/15/16

Gilotrif® (afatinib)*

Boehringer Ingelheim

Squamous cell carcinoma of the lung

Oral

100,000

4/25/16

Cabometyx™ (cabozantinib)

Exelixis

Renal cell carcinoma (RCC)

Oral

17,000 (RCC, 2nd line setting)

5/9/16

Imbruvica® (ibrutinib)*

AbbVie

Small lymphocytic leukemia (SLL)

Oral

CLL/SLL: 115,000

5/13/16

Lenvima® (lenvatinib)*

Eisai

RCC

Oral

17,000 (RCC, 2nd line setting)

5/25/16

Afstyla® (antihemophilic factor [recombinant] single chain)

CSL Behring

Hemophilia A

IV

16,500

5/27/16

Ocaliva® (obeticholic acid)

Intercept

Primary biliary cholangitis

Oral

128,000

5/27/16

Zinbryta™ (daclizumab)

AbbVie and Biogen

Relapsing forms of multiple sclerosis

SubQ

400,000

6/28/16

Epclusa® (sofosbuvir and velpatasvir)

Gilead

Hepatitis C, all genotypes

Oral

2.7–3.9 million

6/30/16

Humira® (adalimumab)*

AbbVie

Uveitis

SubQ

109,000

*Expanded Indication

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Diplomat Clinical Services | Specialty Drug Approvals

3/16/16


Q3 2016

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7/22/16

Viekira XR™ (dasabuvir, ombitasvir, AbbVie paritaprevir, and ritonavir)*

Hepatitis C, genotype 1, once daily formulation

Oral

Genotype 1: 70% in the U.S.

8/30/2016

Erelzi™ (etanerceptszzs)

Multiple indications (Enbrel® biosimilar)

SubQ

Several million

9/13/2016

Cuvitru™(immune globulin Shire subcutaneous [human], 20% solution)

Primary immunodeficiency

SubQ

250,000

9/19/16

Exondys 51™ (eteplirsen)

Sarepta

Duchenne muscular dystrophy

IV

2,300 (with specific genetic mutation)

9/23/16

Amjevita™ (adalimumab-atto)

Amgen

Multiple indications (Humira® biosimilar)

SubQ

Several million

9/23/16

Ilaris® (canakinumab)* Novartis

Periodic fever syndromes

SubQ

Rare, although exact population is not well understood

9/23/16

Stelara® (ustekinumab)*

Janssen

Crohn’s disease

SubQ

Crohn’s: 780,000

9/28/16

Orkambi® (lumacaftor and ivacaftor)*

Vertex

Cystic fibrosis in pediatric patients ages 6–11 with F508del genetic mutation

Oral

2,500 (CF pediatric total patients)

Sandoz

Q4 2016 11/4/16

Selzentry® (maraviroc)*

Viiv

HIV in pediatric patients ages 2 and up

Oral

1.1 million (all HIV)

11/4/16

Enbrel® (etanercept)*

Amgen

Psoriasis in pediatric patients ages 4–17

SubQ

7.5 million (all psoriasis)

11/10/16

Vemlidy® (tenofovir alafenamide)

Gilead

Hepatitis B

Oral

1 million

12/14/16

Eucrisa™ (crisaborole)

Pfizer

Atopic dermatitis

Topical

17.8 million

12/19/16

Rubraca™ (rucaparib)

Clovis

Ovarian cancer

Oral

190,000

12/23/16

Spinraza™ (nusinersen) Biogen

*Expanded Indication

Spinal muscular atrophy Intrathecal

32,000


SPECIALTY DRUG PIPELINE5 Development of novel new drugs, as well as expanded indications for previously approved treatments, continues to make the specialty drug pipeline worth watching. In 2017, it is expected that a fairly wide scope of drugs will enter the market across the specialty disease states discussed previously. It seems reasonable to expect that more novel new oral oncology drugs will be approved in 2017 than 2016. In fact, multiple approvals are forecasted in both breast cancer and blood cancers. Rare disease drugs are also well represented on the 2017 forecast. Some particular drugs to watch in 2017 include: â&#x20AC;˘ Ocrelizumab is expected to be approved in the first quarter of 2017, making it the first drug specifically indicated for primary progressive forms of multiple sclerosis (MS), which affects approximately 15% of MS patients. It will also be a viable treatment option for relapsed-remitting MS, although there is much more competition in that market space. While ocrelizumab is expected to do well, the drug may be supplied to patients mainly outside the specialty pharmacy channel due to the IV route of administration. â&#x20AC;˘ New oral agents for acute myeloid leukemia (AML) are expected to be on the FDA review docket for 2017 and early 2018. Midostaurin has filed with the FDA for AML in patients with FLT-3 genetic mutation and aggressive systemic mastocytosis. Enasidenib is aimed at AML patients with IDH-2 genetic mutation, and the manufacturer has indicated plans to initiate filing with the FDA by the end of 2016. Additionally, gilteritinib has ongoing phase 3 trials in FLT-3+ AML patients. Currently, AML is treated with IV-administered chemotherapy regimens, so safe and effective oral AML drugs could be a welcome addition to the treatment options for these patients. â&#x20AC;˘ Moderate-to-severe atopic dermatitis/eczema may affect more than 17.8 million Americans and currently has limited advanced treatment options. Patients with atopic dermatitis that do not find adequate relief from preventive measures and currently available treatments may benefit from two drugs expected to launch in 2017. Eucrisa (crisaborole) is a topically administered PDE4 inhibitor that was approved on December 14, 2016. Dupilumab is a subcutaneously dosed IL-4 and -13 antagonist with a PDUFA date of March 29, 2017. It remains to be seen if these two agents will be distributed mostly through specialty or retail pharmacies. Given the large patient population and limited treatment options, some analysts see strong potential for these two new dermatological agents.

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2017 Expected Specialty Approvals9 Expected FDA Decision Date

Drug

Target Indication

12

Population (U.S.)

Q1 2017 Baricitinib

Rheumatoid arthritis

Oral

1.3 million

1/24/17

Praluent® (alirocumab)*

Hypercholesterolemia, once-monthly formulation

SubQ

638,000

2/11/17

Deflazacort (MP-104)

Duchenne muscular dystrophy

Oral

16,000

2/17/17

Brodalumab

Psoriasis

SubQ

7.5 million

2/28/17

Telotristat etiprate

Carcinoid syndrome

Oral

3,200

3/28/17

Ocrelizumab

Multiple sclerosis, primary progressive and relapsing forms

IV

4,000 (primary progressive MS), 400,000 (relapsing forms of MS)

3/29/17

Dupilumab

Atopic dermatitis

SubQ

17.8 million

3/30/17

Abaloparatide

Osteoporosis

SubQ

10 million

Q1 2017

Adynovate® Hemophilia A in (antihemophilic pediatric patients and factor recombinant, surgical settings pegylated)*

IV

16,500 (hemophilia A total patients)

Q1 2017

Berinert® (C1 esterase inhibitor, human)*

Hereditary angioedema, new formulation

SubQ

20,000

Q1 2017

Imbruvica® (ibrutinib)*

Marginal zone lymphoma

Oral

12% of B cell lymphomas

Q1 2017

Neratinib

Breast cancer, HER2+

Oral

2.8 million

Q1 2017

N9-GP/NN7999

Hemophilia B

IV

3,400

Q1 2017

Tafinlar® (dabrafenib) and Mekinist® (trametinib)*

Non-small-cell lung cancer (NSCLC), BRAF+

Oral

2.6% of NSCLC patients have this mutation

Q1 2017

Ribociclib

Breast cancer, HR+, HER2-

Oral

1 million

1/19/17

Diplomat Clinical Services | Specialty Drug Approvals

Route


Midostaurin

Early 2017

SB-2 (infliximab) biosimilar

Acute myeloid leukemia (AML), FLT3+ Multiple indications (Remicade® biosimilar)

Oral

7,000 (AML, FLT3+)

IV

Several million

13

Q2 2017 4/3/17

Deutetrabenazine

Huntington’s disease

Oral

17,500

4/11/17

Valbenazine

Tardive dyskinesia

Oral

20–50% of long term users of dopamine blockers and antipsychotics may develop TD

4/27/17

Cerliponase alfa

Batten disease

IV

9,600

4/29/17

Brigatinib

Non-small-cell lung cancer, ALK+

Oral

400,000

6/9/17

CHS-1701 (pegfilgrastim biosimilar)

Febrile neutropenia, acute radiation syndrome (Neulasta® biosimilar)

SubQ

60,000 severe cases/year (febrile neutropenia and acute radiation syndrome combined)

6/30/17

Binimetinib

Melanoma, NRAS+

Oral

1 million

Mid-2017

Edaravone

Amyotrophic lateral sclerosis (ALS)

IV

15,000 to 21,000

Mid-2017

Benlysta® (belimumab)*

Lupus, new formulation

SubQ

89,300

Mid-2017

Enasidenib

AML, IDH2+

Oral

6,000 (AML, IDH2+)

Mid-2017

Niraparib

Ovarian cancer

Oral

190,000

Mid-2017

Ibalizumab

HIV

IV

1.1 million

Mid-2017

Buparlisib

Breast cancer, HR+ and HER2-

Oral

1 million

Mid-2017

CHS-1420 (adalimumab biosimilar)

Multiple indications (Humira® biosimilar)

SubQ

Several million

Mid-2017

Stivarga® (regorafenib)

Hepatocellular carcinoma

Oral

19,100

*Expanded indication (does not include IV or other health care provider–administered oncology products)

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Early 2017


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Tony Lin

Staff Pharmacist


Epclusa® Taltz™ Venclexta™ Zepatier™

16 18 20 22

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2016 Key Approvals

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Epclusa® (velpatasvir and sofosbuvir)11 Hepatitis C

INDICATION Treatment of adult patients with chronic hepatitis C virus (HCV) infection, genotypes 1–6, with or without cirrhosis. Use in combination with ribavirin for patients with decompensated cirrhosis. CLINICAL TRIAL BRIEFING Velpatasvir and sofosbuvir was evaluated for the treatment of hepatitis C in four randomized trials composed of 1,825 total patients. As a group, the trials were composed of patients with genotypes 1–6, including those with or without cirrhosis (both compensated and decompensated), as well as treatment-naive and treatment-experienced patients. Patients on study received velpatasvir and sofosbuvir with or without ribavirin, sofosbuvir, and ribavirin, or a placebo, for 12 or 24 weeks. The primary endpoint of each study was sustained virologic response 12 weeks after the completion of dosing (SVR 12). Across all studies, SVR 12 in patients given velpatasvir and sofosbuvir with or without ribavirin ranged from 85% (velpatasvir, sofosbuvir, and ribavirin dosed for 12 weeks in Genotype 3 patients with decompensated cirrhosis) to 100% (multiple patient groups).


DOSING One tablet orally once daily with or without food. For patients without cirrhosis or with compensated cirrhosis (Child-Pugh A), take velpatasvir and sofosbuvir for 12 weeks. For patients with decompensated cirrhosis (Child-Pugh B and C), take velpatasvir and sofosbuvir in combination with ribavirin for 12 weeks. SAFETY Common Adverse Events: Velpatasvir and sofosbuvir: headache and fatigue Velpatasvir, sofosbuvir, and ribavirin: fatigue, anemia, nausea, headache, insomnia, and diarrhea Serious Adverse Events: Bradycardia with amiodarone coadministration OTHER AGENTS IN THERAPEUTIC AREA • Daklinza™ (daclatasvir) • Harvoni® (ledipasvir and sofosbuvir) • Olysio® (simeprevir) • Sovaldi® (sofosbuvir) • Technivie™ (ombitasvir, paritaprevir, and ritonavir) • Viekira Pak™ and Viekira XR™ (ombitasvir, paritaprevir, ritonavir, and dasabuvir) • Zepatier™ (elbasvir and grazoprevir)

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Diplomat Clinical Services | Specialty Drug Approvals

APPROVAL DATE: June 28, 2016 MANUFACTURER: Gilead CLASS: NS5A inhibitor and NS5B polymerase inhibitor STORAGE: Below 30°C (86°F); dispense only in original container HOW SUPPLIED: Tablets containing 100 mg of velpatasvir and 400 mg of sofosbuvir PATIENT POPULATION: Approximately 2.7–3.9 million patients with hepatitis C in the U.S.


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Taltz™ (ixekizumab)13 Psoriasis

INDICATION Treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy. CLINICAL TRIAL BRIEFING Ixekizumab was evaluated for the treatment of psoriasis in three multicenter, randomized, double-blind, placebo-controlled trials composed of 3,866 total patients. Patients on study received either 80 mg of ixekizumab every two weeks (following a 160 mg initial dose), 50 mg of etanercept twice weekly (two of three trials), or placebo for 12 weeks. The primary endpoints of the studies were the proportion of patients achieving at least 75% reduction in Psoriasis Area Severity Index (PASI 75) and a static Physician’s Global Assessment (sPGA) score of 0 or 1 with at least a two-point improvement. Across the three studies, PASI 75 achievement ranged from 87–90% for patients given ixekizumab, 41% for etanercept, and 2–7% for patients given placebo. sPGA score of 0 or 1 was achieved by 81–83% of patients given ixekizumab, 27% of those on etanercept, and 3–7% of patients given placebo.


DOSING Administer by subcutaneous injection. The recommended initial dose is 160 mg (Week 0), followed by 80 mg given at weeks 2, 4, 6, 8, 10, and 12, followed by 80 mg every four weeks thereafter. SAFETY Common Adverse Events: Injection site reactions, upper respiratory tract infections, nausea, and tinea infections Serious Adverse Events: Infections, tuberculosis reactivation, hypersensitivity, exacerbations of inflammatory bowel disease OTHER AGENTS IN THERAPEUTIC AREA • Cosentyx® (secukinumab) • Enbrel® (etanercept) • Humira® (adalimumab) • Otezla® (apremilast) • Remicade® (infliximab) • Stelara® (ustekinumab)

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Diplomat Clinical Services | Specialty Drug Approvals

APPROVAL DATE: March 22, 2016 MANUFACTURER: Eli Lilly CLASS: IL-17A antagonist STORAGE: 2–8°C (36–46°F); protect from light; do not freeze or shake HOW SUPPLIED: 80 mg/mL single-dose syringe or autoinjector PATIENT POPULATION: 7.5 million in the U.S.


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Venclextaâ&#x201E;˘ (venetoclax)18 Oncology

INDICATION Treatment of chronic lymphocytic leukemia (CLL) for patients with 17p deletion, as detected by an FDA approved test, and who have received at least one prior therapy. CLINICAL TRIAL BRIEFING Venetoclax was evaluated for the treatment of CLL for patients with 17p deletion in an open-label, single-arm, multicenter study composed of 106 patients. Patients on study tested positive for 17p deletion and had received at least one prior treatment. Venetoclax was administered daily with 20 mg given each day during Week 1, 50 mg during Week 2, 100 mg during Week 3, 200 mg during Week 4, and 400 mg thereafter. Administration continued until disease progression or unacceptable toxicity occurred. Overall response rate (ORR) was evaluated by an Independent Review Committee (IRC) using International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines. ORR was 80.2% (95% CI: 71.3, 87.3). Additionally, the median time to first response was 0.8 months (ranging from 0.1 to 8.1 months). Median duration of response (DOR) had not been reached at the time of analysis. Approval was granted under the FDAâ&#x20AC;&#x2122;s accelerated approval program based on ORR. Continued approval may depend on the outcome of ongoing confirmatory clinical trials.


DOSING One tablet orally once daily with a meal and water at approximately the same time each day. Coadministration with antihyperuricemics and adequate hydration are recommended due to risk of tumor lysis syndrome. Increase the daily dose of venetoclax according to the following schedule: Week 1: 20 mg daily Week 2: 50 mg daily Week 3: 100 mg daily Week 4: 200 mg daily Week 5 and beyond: 400 mg daily SAFETY Common Adverse Events: Neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigue Serious Adverse Events: Tumor lysis syndrome, neutropenia, risk of interaction with live attenuated vaccines, and embryo-fetal toxicit OTHER AGENTS IN THERAPEUTIC AREA • Imbruvica® (ibrutinib) • Zydelig® (idelalisib)

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Diplomat Clinical Services | Specialty Drug Approvals

APPROVAL DATE: April 11, 2016 MANUFACTURER: AbbVie CLASS: PCSK9 inhibitor STORAGE: At or below 30°C (86°F) HOW SUPPLIED: 10, 50, and 100 mg tablets PATIENT POPULATION: 18,960 new diagnoses of chronic lymphocytic leukemia (CLL) in 2016. Approximately 20% of patients with relapsed CLL have 17p deletion.


Diplomat Clinical Services | Specialty Drug Approvals

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Zepatierâ&#x201E;˘ (elbasvir and grazoprevir)12 Hepatitis C

INDICATION Treatment of adult patients with chronic hepatitis C virus (HCV) who have genotype 1 or 4 infection. CLINICAL TRIAL BRIEFING Elbasvir and grazoprevir was evaluated in two placebo-controlled trials and four uncontrolled trials composed of 1,401 total patients with HCV genotype 1, 4, or 6. Overall, the studies included a variety of patient types including those who were treatment naĂŻve or experienced, with or without cirrhosis, coinfected with HIV, and/or had severe renal impairment. Patients on study received 50 mg elbasvir and 100 mg grazoprevir with or without ribavirin for 12 or 16 weeks. The primary endpoint in all studies was sustained virologic response 12 weeks after the end of treatment (SVR12). Across all patient types in all studies SVR12 ranged from 86% (six of seven patients with severe renal impairment and cirrhosis given elbasvir and grazoprevir for 12 weeks) to 100% (multiple patient types).


DOSING Prior to the initiation of treatment for genotype 1a, testing for NS5A resistanceassociated polymorphisms is recommended. Administer one tablet orally once daily with or without food. Depending on patient type, treatment duration is 12 or 16 weeks and may be used with or without ribavirin. See prescribing information for further details. SAFETY Common Adverse Events: Elbasvir and grazoprevir: fatigue, headache, and nausea Elbasvir, grazoprevir, and ribavirin: anemia and headache Serious Adverse Events: ALT elevation OTHER AGENTS IN THERAPEUTIC AREA • Daklinza™ (daclatasvir) and Sovaldi® (sofosbuvir) • Epclusa® (velpatasvir and sofosbuvir) • Harvoni® (ledipasvir and sofosbuvir) • Olysio® (simeprevir) and Sovaldi® (sofosbuvir) • Technivie® (ombitasvir, paritaprevir, and ritonavir) • Viekira™ and Viekira XR™ (dasabuvir, ombitasvir, paritaprevir, and ritonavir)

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Diplomat Clinical Services | Specialty Drug Approvals

APPROVAL DATE: Jan. 28, 2016 MANUFACTURER: Merck CLASS: NS5A inhibitor and NS3/4A protease inhibitor STORAGE: 20–25°C (68–77°F) with excursions permitted between 15–30°C (59–86°F); store in the original package HOW SUPPLIED: Tablets containing 50 mg of elbasvir and 100 mg of grazoprevir PATIENT POPULATION: Genotype 1: 70% of HCV patients in the U.S.; Genotype 4: 1% of HCV patients in the U.S.


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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 preclinical 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. Novel Drug Approvals for 2016. U.S. Food & Drug Administration Website. http://www.fda.gov/Drugs/DevelopmentApprovalProcess/ DrugInnovation/ucm483775.htm. Accessed Dec. 28, 2016. 2. 2016 Biological License Application Approvals. U.S. Food & Drug Administration Website. http://www.fda.gov/BiologicsBloodVaccines/ DevelopmentApprovalProcess/BiologicalApprovalsbyYear/ucm482397.htm. Accessed Dec. 6, 2016. 3. Diplomat Clinical Services. Specialty Drug Approvals: 2015 Highlights + 2016 Projections. ISSUU Website. https://issuu.com/diplomatrx/ docs/specialty_drug_approvals_2015_highl_7a4d31141f4d2f. Accessed Dec. 28, 2016. 4. Search Orphan Designations and Approvals. U.S. Food & Drug Administration Website. http://www.accessdata.fda.gov/scripts/opdlisting/ oopd/. Accessed Dec. 6, 2016. 5. Cortellis™. Thomson Reuters. https://cortellis.thomsonreuterslifesciences.com/ngg/login.do. Accessed Dec. 13, 2016. 6. Exondys 51™ [package insert]. Cambridge, MA: Sarepta: 2016. 7. FDA grants accelerated approval to first drug for Duchenne muscular dystrophy. FDA Website. http://www.fda.gov/NewsEvents/Newsroom/ 8. FDA approves Ocaliva® for rare, chronic liver disease. FDA Website. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ ucm503964.htm. Accessed Nov. 29, 2016. 9. FDA approves first treatment for rare disease in patients who receive stem cell transplant from blood or bone marrow. FDA Website. http:// www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm493225.htm. Accessed Nov. 29, 2016. 10. New Indications & Dosage Forms for Existing Drugs. Drugs.com Website. https://www.drugs.com/new-indications.html. Accessed Dec. 6, 2016. 11. Epclusa® [package insert]. Foster City, CA: Gilead: 2016. 12. Zepatier™ [package insert]. Whitehouse Station, NJ: Merck: 2016. 13. Taltz™ [package insert]. Indianapolis, IN: Eli Lilly: 2016. 14. Zinbryta™ [package insert]. Cambridge, MA: Biogen and North Chicago, IL: AbbVie: 2016. 15. Types of MS. National Multiple Sclerosis Society Webpage. http://www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed Dec. 6, 2016. 16. Eczema Prevalence in the United States. National Eczema Associate Website. https://nationaleczema.org/research/eczema-prevalence/. Accessed Dec. 5, 2016. 17. New Drug Approvals. Drugs.com Website. https://www.drugs.com/newdrugs.html. Accessed Dec. 28, 2016. 18. Venclexta™ [package insert]. North Chicago, IL: AbbVie: 2016.


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Diplomat 2016 Pipeline Recap  
Diplomat 2016 Pipeline Recap