Q2 2016 Specialty Pipeline Report

Specialty Pipeline Report

2ND QUARTER 2016

FORWARD-LOOKING STATEMENTSThis 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 December 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.

INDUSTRY AND MARKET DATACertain information contained in this publication concerning our industry and the markets in which we operate is based on information from publicly available independent industry and research organizations and other third-party sources, and management estimates. Management estimates are derived from publicly available information released by independent industry and research analysts and 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.

PREFACE .......................................................................................................................................5RECENT APPROVALS ...................................................................................................................6 Zepatier™ (elbasvir + grazoprevir) ............................................................................. 7 Descovy® (emtricitabine + tenofovir alafenamide) .................................................8 Odefsey® (emtricitabine + tenofovir alafenamide + rilpivirine) .............................9 Taltz® (ixekizumab) .................................................................................................... 10 Venclexta™ (venetoclax) .............................................................................................11TOP AGENTS TO ANTICIPATE .....................................................................................................12 Cabozantinib ...............................................................................................................13 Zinbryta™ (daclizumab) ..............................................................................................14 Deutetrabenazine ......................................................................................................15 Obeticholic acid ..........................................................................................................16 Rociletinib ....................................................................................................................17 Velpatasvir + sofosbuvir ............................................................................................19RECENT SPECIALTY DRUG APPROVALS ...................................................................................20LATE STAGE AGENTS .................................................................................................................22NEW INDICATIONS, FORMULATIONS AND DOSE MODIFICATIONS .......................................24 GLOSSARY ..................................................................................................................................26 REFERENCES ...........................................................................................................................27

Table of Contents

AT D I P LO M AT, we blend clinical excellence with a personal touch— for happier livesand health that lasts.

specialty pipeline report - Q2 2016 5

Preface 1, 2, 3

With thousands of clinical trials underway and only a fraction of agents reaching a rapidly evolving marketplace, strategic planning for specialty pharmaceuticals can be a challenging and daunting task. In our commitment to provide timely and valuable specialty medication news to our partners, Diplomat Specialty Pharmacy is pleased to provide you our Specialty Pipeline Report. This quarterly report, dedicated exclusively to specialty products, provides insight on both upcoming and recently approved medications expected to impact the specialty landscape and your business.

Each Specialty Pipeline Report begins by detailing selected Recent Approvals that have been approved by the US Food and Drug Administration (FDA) during the previous quarter. The following section, Top Agents to Anticipate, targets specific promising specialty medications expected to have significant therapeutic and market impact after approval. The Recent Specialty Drug Approvals table is an overview of all specialty drugs approved in the previous quarter. A more comprehensive review of

the pipeline is provided in the Late Stage Agents table, which includes agents in later stages of phase III trials or those for which new drug applications (NDA) or biologic license applications (BLA) have been filed with the FDA. This table includes products that are expected to have an FDA decision within the year. The New Indications, Combinations and Formulations table provides information regarding currently approved specialty medications that are seeking approval for new indications, combinations or formulations.

In each section, pipeline agents are presented with a description of an upcoming event which is generally a Prescription Drug User Fee Act (PDUFA) date. PDUFA authorizes the FDA to collect fees from drug sponsors, thus generating funding to expedite the drug review and approval process. This establishes two tiers (standard versus priority) from which the FDA sets a target date, or PDUFA date, for its review.

Sales projections at the time of printing are reported in U.S. dollars (millions); global data may be

substituted when US information is unavailable. The statuses below appear throughout the report and represent the medication’s classification within the FDA approval process.1,2

The accelerated approval pathway permits earlier approval of therapies developed for serious conditions with a currently unmet medical need. This designation may be based on surrogate endpoints, with post-marketing trials to verify clinical outcomes.

Breakthrough therapy designation provides for expedited development and review of drugs that treat serious or life-threatening conditions and demonstrate impressive preliminary clinical data. Breakthrough designation holds the same advantages as fast track designation with the addition of intensive FDA guidance for efficient drug development.

The fast track designation is designed to increase patient access to critical drugs that treat serious conditions with a currently unmet

medical need by facilitating a quick and efficient development and review process. Many fast track medications also receive a priority review.

Orphan drug status is granted to drugs and biologics which are intended to diagnose, prevent, or treat rare diseases and disorders that affect less than 200,000 people in the United States. A product with a greater target population may also qualify if the sponsor is not expected to recover its development and marketing costs.

A priority review designation is granted to drugs that are considered major therapeutic advancements or those used to treat conditions currently lacking adequate therapy. This status shortens the goal for FDA review from 10 to six months.

6

Recent approvals


APPROVAL DATE: Jan. 28, 2016MANUFACTURER: MerckCLASS: S5A inhibitor + NS3/4 protease inhibitor

STORAGE: 20°C to 25°C (68°F to 77°F) with excursions permitted between 15°C to 30°C (59°F to 86°F), store in the original package

HOW SUPPLIED: Tablets containing 50 mg of elbasvir and 100 mg of grazoprevirPATIENT POPULATION: Genotype 1 - 70% of HCV patients in the U.S.; genotype 4 - 1% of HCV patients in the U.S.

Zepatier™ (elbasvir + grazoprevir) 4,5

INDICATIONTreatment of adult patients with chronic hepatitis C (HCV) who have genotype 1 or 4 infection.

CLINICAL TRIAL BRIEFINGElbasvir + 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 naïve or experienced, with or without cirrhosis, co-infected with HIV, and/or had severe renal impairment. Patients on study received 50 mg elbasvir + 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 + grazoprevir for 12 weeks) to 100% (multiple patient types).

DOSINGPrior to the initiation of treatment for genotype 1a, testing for NS5A resistance-associated polymorphisms

Recent approvals Hepatitis C

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.

SAFETYCommon Adverse Events: Elbasvir + grazoprevir: fatigue, headache, and nauseaElbasvir + grazoprevir + ribavirin: anemia and headache Serious Adverse Events: ALT elevation

OTHER AGENTS IN THERAPEUTIC AREA • Daklinza™ (daclatasvir) + Sovaldi®

(sofosbuvir) • Harvoni® (ledipasvir + sofosbuvir) • Olysio® (simeprevir) + Sovaldi®

(sofosbuvir) • Technivie® (ombitasvir + paritaprevir +

ritonavir) • Viekira™ (dasabuvir + ombitasvir +

paritaprevir + ritonavir)

USDm – US Dollars, millions Biopharm Insight; Accessed March 1, 2016

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PROJECTED US SALES (USDm)

8

APPROVAL DATE: April 4, 2016MANUFACTURER: GileadCLASS: Nucleoside analog reverse transcriptase inhibitors (NRTIs)

STORAGE: Below 30°C (86°F), keep container tightly closed, dispense only in the original container

HOW SUPPLIED: Co-formulated tablets containing 200 mg of emtricitabine (FTC) and 25 mg of tenofovir alafenamide (TAF)PATIENT POPULATION: 1.2 million patients in the U.S.

Descovy® (emtricitabine + tenofovir alafenamide) 4,6

INDICATIONTreatment of HIV-1 infection in adults and pediatric patients 12 years and older when used on combination with other antiretroviral agents.

CLINICAL TRIAL BRIEFINGEmtricitabine (FTC) + tenofovir alafenamide (TAF) was evaluated in combination with elvitegravir (EVG) + cobicistat (COBI) in studies composed of a total of 1,936 patients. Included in the studies were patients with no past antiretroviral treatment history and those replacing another previously stable antiretroviral regimen. Virologic response rates (defined as HIV-1 RNA < 50 copies per mL) were evaluated after 24 and 48 weeks. Across all studies, virologic response rates ranged from 91% to 95%.

DOSINGTake one tablet orally once daily with a meal. Prior to the initiation of treatment, patients should be tested for hepatitis B infection. Estimated creatinine clearance, urine glucose and urine protein should be evaluated.

HIV

SAFETYCommon Adverse Events: NauseaSerious Adverse Events: Redistribution/accumulation of body fat, immune reconstitution syndrome, new onset or worsening of renal impairment, bone loss and mineralization defectsBlack Box Warning: Lactic acidosis, severe hepatomegaly with steatosis, and severe acute exacerbation of hepatitis B in patients co-infected with HIV-1 and hepatitis B that discontinue treatment

OTHER AGENTS IN THERAPEUTIC AREA • Combivir® (zidovudine + lamivudine) • Emtriva® (emtricitabine) • Epivir® (lamivudine) • Epzicom® (abacavir + lamivudine) • Retrovir® (zidovudine) • Trizivir® (abacavir + zidovudine +

lamivudine) • Truvada® (tenofovir disoproxil fumarate

+ emtricitabine) • Videx® (didanosine) • Viread® (tenofovir disoproxil fumarate) • Zerit® (stavudine) • Ziagen® (abacavir)

PROJECTED SALES NOT AVAILABLE

Recent approvals


APPROVAL DATE: March 1, 2016MANUFACTURER: GileadCLASS: HIV nucleoside analog reverse transcriptase inhibitors (NRTI) + non-nucleoside reverse transcriptase inhibitor (NNRTI)

STORAGE: Below 30°C (86°F), keep container tightly closed, dispense only in the original containerpackage

HOW SUPPLIED: Co-formulated tablets containing 200 mg of emtricitabine (FTC), 25 mg of tenofovir alafenamide (TAF), and 25 mg of rilpivirine (RPV)PATIENT POPULATION: 1.2 million patients in the U.S.

Odefsey® (emtricitabine + tenofovir alafenamide + rilpivirine) 4,7

HIV

INDICATIONComplete treatment regimen for patients with HIV-1 infection who are 12 years of age or older. See prescribing information for further details.

CLINICAL TRIAL BRIEFINGFTC + TAF + RPV was evaluated as treatment for HIV-1 infection in studies composed of a total of 867 patients. Included in the studies were patients with no past antiretroviral treatment history and those replacing another previously stable antiretroviral regimen. Virologic response rates (defined as HIV-1 RNA < 50 copies per mL) were evaluated after 48 and 96 weeks. Virologic response rates in one study ranged from 68% (patients with baseline CD4+ cell count less than 200 cells/mm3) to 89% (patients previously on a stable antiretroviral regimen). In a study of FTC + TAF + RPV in patients age 12 to less than 18, virologic response rate was 80%.

DOSINGTake one tablet orally once daily with a meal. Prior to the initiation of treatment, patients should be tested for hepatitis B infection. Estimated creatinine clearance, urine glucose and urine protein should be evaluated. HIV-1 RNA values should be monitored while taking FTC + TAF + RPV.

SAFETYCommon Adverse Events: Depressive disorders, insomnia, headache and nauseaSerious Adverse Events: Skin and hypersensitivity reactions, increased risk of Torsade de Pointes when used concomitantly with drugs known to prolong QTc interval, depressive disorders, hepatotoxicity, redistribution/accumulation of body fat, immune reconstitution syndrome, renal impairment, bone loss and mineralization defectsBlack Box Warning: Lactic acidosis, severe hepatomegaly with steatosis, and severe acute exacerbation of hepatitis B in patients co-infected with HIV-1 and hepatitis B that discontinue treatment

OTHER AGENTS IN THERAPEUTIC AREA • Atripla® (efavirenz + tenofovir disoproxil

fumarate + emtricitabine) • Complera® (emtricitabine + tenofovir

disoproxil fumarate + rilpivirine) • Genvoya® (elvitegravir + tenofovir

alafenamide fumarate + emtricitabine + cobicistat)

• Stribild® (elvitegravir + cobicistat + tenofovir disoproxil fumarate + emtricitabine)

• Triumeq® (dolutegravir + abacavir + lamivudine)

PROJECTED SALES NOT AVAILABLE

Recent approvals

10

APPROVAL DATE: March 22, 2016MANUFACTURER: Eli Lilly

CLASS: IL-17A antagonistSTORAGE: 2°C to 8°C (36°F to 46°F), protect from light, do not freeze or shake

HOW SUPPLIED: 80 mg/mL single-dose syringe or autoinjectorPATIENT POPULATION: 7.5 million in the U.S.

Taltz™ (ixekizumab)4,8

INDICATIONTreatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

CLINICAL TRIAL BRIEFINGIxekizumab 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 2 weeks (following a 160 mg initial dose), 50 mg of etanercept twice weekly, 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 2-point improvement. Across the three studies, PASI 75 achievement ranged from 87% to 90% for patients given ixekizumab and 2% to 7% for patients given placebo. sPGA score of 0 or 1 was achieved by 81% to 83% of patients given ixekizumab and 3% to 7% of patients given placebo.

DOSINGAdminister 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 4 weeks thereafter.

Psoriasis

SAFETYCommon Adverse Events: Injection site reactions, upper respiratory tract infections, nausea, and tinea infectionsSerious 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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Recent approvals


APPROVAL DATE: April 11, 2016MANUFACTURER: AbbVieCLASS: BCL-2 inhibitor

STORAGE: At or below 30°C (86°F)HOW SUPPLIED: 10, 50 and 100 mg tablets

PATIENT POPULATION: 15,000 new diagnoses of chronic lymphocytic leukemia (CLL) yearly. Approximately 20% of patients with relapsed CLL have 17p deletion.

Venclexta™ (venetoclax)4,9

Oncology

INDICATIONTreatment 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 BRIEFINGVenetoclax 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, and 400 mg during week 4 and beyond. 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.

DOSINGAdminister orally once daily with a meal and water at approximately the same time each day. Co-administration with anti-hyperuricemics 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 dailyWeek 2 – 50 mg dailyWeek 3 – 100 mg dailyWeek 4 – 200 mg dailyWeek 5 and beyond – 400 mg daily

SAFETYCommon Adverse Events: Diarrhea, Neutropenia, diarrhea, nausea, anemia, upper respiratory tract infection, thrombocytopenia, and fatigueSerious Adverse Events: Tumor lysis syndrome, neutropenia, risk of interaction with live attenuated vaccines, and embryo-fetal toxicity OTHER AGENTS IN THERAPEUTIC AREA • Imbruvica® (ibrutinib) • Zydelig® (idelalisib)


USDm – US Dollars, millions Biopharm Insight; Accessed April, 12, 2016

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12

Top agents to anticipate


MANUFACTURER: ExelixisALIAS: Cometriq®, BMS-907351, XL-184CLASS: Kinase inhibitor

TARGET INDICATION: Renal cell carcinoma (RCC) after one previous treatmentPATIENT POPULATION: 17,000 in the U.S.

ROUTE: OralCURRENT STATUS: FDA filing completed

Cabozantinib 4,10

CLINICAL TRIAL BRIEFINGCabozantinib was evaluated for the treatment of renal cell carcinoma in a randomized, open-label, phase 3 trial composed of 658 patients who had progressed after a VEGFR therapy. Patients on study received 60 mg of cabozantinib or 10 mg of everolimus once daily as long as clinical benefit continued or until unacceptable adverse events occurred. Dose adjustments were made as necessary for each individual patient. The primary endpoint of the study was progression-free survival (PFS). Secondary endpoints included overall survival (OS) and objective response rate (ORR). Median PFS was 7.4 months for the cabozantinib group and 3.8 months for the everolimus group. The rate of progression or death was reduced by 42% in the cabozantinib group compared to everolimus (p<0.001). ORR was 21% for cabozantinib and 5% for everolimus (p<0.005). At the interim analysis, the difference in OS was not statistically significant between the two groups.


SAFETYThe most common adverse events in patients given cabozantinib were diarrhea, fatigue, nausea, decreased appetite, and palmar-plantar erythrodysesthesia syndrome. Overall, adverse events occurred in 100% of patients in the cabozantinib group and >99% of patients in the everolimus group.

UPCOMING EVENTPDUFA – June 22, 2016

STATUSBreakthrough, fast track, and priority review

Oncology


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MANUFACTURER: Biogen and AbbVieALIAS: DAC HYP, BIIB-019, ZenapaxCLASS: IL-2 receptor antagonist

TARGET INDICATION: Relapsing-remitting multiple sclerosis PATIENT POPULATION: 400,000 in the U.S.

ROUTE: SubcutaneousCURRENT STATUS: FDA filing completed

CLINICAL TRIAL BRIEFINGDaclizumab was evaluated for the treatment of relapsing-remitting multiple sclerosis in a randomized, double-blind, active-controlled, phase 3 study composed of 1,841 patients. Patients in the study received 150 mg of daclizumab every 4 weeks or 30 µg of interferon beta-1a once weekly for up to 144 weeks. The primary endpoint of the study was annualized relapse rate. Patients in the daclizumab group had 0.22 annual relapses compared to 0.39 relapses for the interferon beta-1a group, corresponding to a 45% lower relapse rate (p<0.001) in favor of daclizumab. The number of new or newly enlarged hyperintense lesions was 4.3 in the daclizumab group compared to 9.4 in the interferon beta-1a group (p<0.001). Additionally, the estimated incidence of disability progression confirmed at 12 weeks was 16% for daclizumab and 20% for interferon beta-1a (p=0.16).

SAFETYThe most common adverse events, not including multiple sclerosis relapse, were nasopharyngitis, headache, upper respiratory tract infection, pyrexia, injection-site pain, urinary tract infection, influenza-like illness, infection, cutaneous events and hepatic events.

UPCOMING EVENTFDA decision in Q2, 2016

STATUSNone

Zinbryta™ (daclizumab) 4,11

Multiple Sclerosis



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CLINICAL TRIAL BRIEFINGDeutetrabenzine was evaluated for the treatment of chorea associated with Huntington’s disease in two phase 3 studies. One of the studies was a double-blind, placebo-controlled, parallel-group trial composed of 90 patients. Patients on study received deutetrabenazine or placebo for 12 weeks at dose levels ranging from 6 mg once daily to 24 mg twice daily with titration and other dosing adjustments made as needed for each individual patient. The primary endpoint of this study was the change from baseline in Total Maximal Chorea (TMC) score rated on the Unified Huntington’s Disease Rating Scale (UDRS). Patients given deutetrabenazine achieved a 2.5 point improvement (p<0.0001) compared to placebo. The other open-label study involved switching 37 patients previously on tetrabenazine to deutetrabenazine for 4 weeks. After switching treatments, TMC score was approximately one point lower compared to baseline after patients were given deutetrabenazine.

SAFETYThe most frequently reported adverse events were somnolence, falls, and nasopharyngitis.

UPCOMING EVENTFDA decision in Q2 2016

STATUSOrphan

MANUFACTURER: TevaALIAS: SD-809CLASS: VMAT2 inhibitor

TARGET INDICATION: Chorea associated with Huntington’s diseasePATIENT POPULATION: 3–7 patients / 100,000 people


Deutetrabenazine 4,12

Rare Diseases

USDm – US Dollars, millions Biopharm Insight; Accessed: March 14, 2016

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MANUFACTURER: InterceptALIAS: OCA, INT-747, DSP-1747CLASS: Farnesoid X receptor agonist

TARGET INDICATION: Primary biliary cirrhosisPATIENT POPULATION: 1 in 1,000 women over 40 years of age


CLINICAL TRIAL BRIEFINGObeticholic acid was evaluated for the treatment of primary biliary cirrhosis in a multinational, double-blind, placebo-controlled phase 3 study composed of 216 patients who could not tolerate or had not responded adequately to ursodeoxycholic acid (UDCA). Patients on study were given 5 or 10 mg of obeticholic acid or placebo once daily for 12 months. The primary endpoint was the proportion of patients achieving alkaline phosphatase (ALP) levels below 1.67 times the upper limit of normal (ULN), an ALP decrease of at least 15% from baseline, and a normal total bilirubin level after 12 months of treatment. After 6 months, patients in the 5 mg group were titrated to the 10 mg group if they demonstrated an inadequate response. The primary endpoint goal was met in 47% of patients receiving 10 mg obeticholic acid, 46% of patients in the titration group, and 10% in the placebo group (p<0.0001). Mean decrease in ALP level compared to baseline was observed in 39% of patients in the 10 mg group, 33% in the titration group, and 5% for the placebo group (p<0.0001).

Total bilirubin was significantly reduced in the 10 mg and titration groups (p<0.05). Additionally, patients receiving obeticholic acid demonstrated significant decreases in selected other liver function parameters.

SAFETYThe most commonly observed adverse event was pruritus.

UPCOMING EVENTPDUFA – May 29, 2016

STATUSFast track, orphan, priority review

Obeticholic acid 4,13,14

Rare Diseases

USDm – US Dollars, millions Biopharm Insight; Accessed: March 23, 2016

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CLINICAL TRIAL BRIEFINGRociletinib was evaluated for the treatment of non-small cell lung cancer in a phase 1-2 study composed of 456 patients with EGFR genetic mutation, including patients with T790 genetic mutation, who had disease progression after receiving treatment with a currently available EGFR inhibitor. Rociletinib was administered at dose levels ranging from 500 to 1,000 mg daily. Progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and disease control rate (DCR) were determined. At the initial evaluations, patients with T790 genetic mutation given 500 or 625 mg of rociletinib demonstrated a PFS of 8.0 months. Originally reported ORR for the 500 mg group was 60% and a DCR of 90%. The FDA requested additional information after it was determined that the initial New Drug Application (NDA) submitted contained immature data including both confirmed and unconfirmed responses. The revised ORR including only confirmed responses was 28% for the 500 mg group and 34% for the 625 mg group with a 9 month DoR for both groups.

SAFETYThe most commonly observed adverse events included hyperglycemia, diarrhea, fatigue, decreased appetite, muscle spasms, weight loss and vomiting.


STATUSBreakthrough, orphan, priority review

MANUFACTURER: ClovisALIAS: CO-1686, AVL-301CLASS: EGFR inhibitor

TARGET INDICATION: Non–small cell lung cancer in patients with T790 genetic mutationPATIENT POPULATION: 24,000 patients in the U.S.


Rociletinib 4,15,16

Oncology

PROJECTED U.S. SALES (USDm)


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18

MANUFACTURER: GileadALIAS: GS-5816CLASS: NS5A inhibitor, nucleotide analog polymerase inhibitor

TARGET INDICATION: Hepatitis C, pan-genotypicPATIENT POPULATION: 4.4 million patients in the U.S.


CLINICAL TRIAL BRIEFINGVelpatasvir + sofosbuvir was evaluated for the treatment of hepatitis C, genotypes 1–6, in four international phase 3 clinical studies. Three of the studies totaled 1,035 patients and involved a variety of patient types including genotypes 1–6, treatment naïve and experienced, and those with or without compensated cirrhosis. A fixed-dose of velpatasvir + sofosbuvir was administered once daily for 12 weeks for these three studies. The fourth study was composed of 267 patients with decompensated cirrhosis and patients received either velpatasvir + sofosbuvir for 12 weeks with or without ribavirin or velpatasvir + sofosbuvir for 24 weeks. The primary endpoint for all studies was sustained virologic response 12 weeks after the completion of treatment (SVR 12). Across the three studies, 98% of all patients achieved SVR 12. Among specific groups in these studies receiving velpatasvir + sofosbuvir, SVR 12 ranged from 95% to 100%. In the fourth study involving patients with decompensated cirrhosis, SVR 12 ranged from 83% to 94%.

SAFETYThe most commonly reported adverse events included headache, fatigue and nausea.


STATUSBreakthrough, priority review

Velpatasvir + Sovaldi® (sofosbuvir) 4,17

Hepatitis C


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DRUG NAME APPROVEDINDICATION(S)

DRUG CLASSMECHANISM ROUTE APPROVAL DATE

Afinitor® (everolimus)Progressive, well-differentiated, non-functional gastrointestinal and lung origin neuroendocrine tumors (NET)*

mTOR inhibitor Oral February 26, 2016

Cinqair® (reslizumab) Asthma with an eosinophilic phenotype IL-5 antagonist IV March 23, 2016

Cosentyx® (secukinumab) Ankylosing spondylitis and psoriatic arthritis* IL-17A antagonist Sub-Q January 15, 2016

Daklinza® (daclatasvir)Hepatitis C, genotypes 1 or 3 with HIV-1

co-infection, advanced cirrhosis, or post-liver transplant infection*

NS5A inhibitor Oral February 5, 2016

Defitelio® (defibrotide) Hepatic veno-occlusive disease Mechanism of action not understood IV March 30, 2016

Descovy® (emtricitabine + tenofovir alafenamide) HIV NRTI Oral April 4, 2016

Harvoni® (ledipasvir + sofosbuvir)

Hepatitis C, genotype 1 or 4 patients with post-liver transplant infection

and genotype 1 patients with decompensated cirrhosis*

NS5A inhibitor + nucleotide analog NS5B polymerase inhibitor Oral February 12, 2016

Ibrance® (palbociclib) HR+, HER2- metastatic breast cancer in combination with fulvestrant* CDK4/6 inhibitor Oral &

Injection February 19, 2016

Idelvion® (coagulation factor IX, recombinant) Hemophilia B Factor IX IV March 4, 2016

Imbruvica® (ibrutinib) First-line treatment for chronic lymphocytic leukemia (CLL)* BTK inhibitor Oral March 4, 2016

Recent Specialty Drug Approvals18,19


DRUG NAME APPROVEDINDICATION(S)

DRUG CLASSMECHANISM ROUTE APPROVAL DATE

Inflectra™ (infliximab-dyyb) biosimilar

Crohn’s disease, ulcerative colitis, rheumatoid arthritis, ankylosing

spondylitis, psoriatic arthritis, psoriasisTNF blocker IV April 5, 2016

Kovaltry® (anti-hemophilic factor, recombinant) Hemophilia A Factor VIII IV March 16, 2016

Odefsey® (emtricitabine + rilpivirine + tenofovir alafenamide) HIV ART regimen Oral March 1, 2016

Taltz® (ixekizumab) Psoriasis IL-17A antagonist Oral March 22, 2016

Venclexta™ (venetoclax) Chronic lymphocytic leukemia (CLL) with 17p deletion BCL-2 inhibitor Oral April 11, 2016

Xalkori® (crizotinib) Non-small cell lung cancer with ROS1 genetic mutation* ALK inhibitor Oral March 11, 2016

Xeljanz® (tofacitinib) Once daily formulation for rheumatoid arthritis* JAK inhibitor Oral February 24, 2016

Zepatier™ (elbasvir + grazoprevir) Hepatitis C, genotypes 1 and 4 NS5A inhibitor + NS3/4A protease inhibitor Oral January 28, 2016

Recent Specialty Drug Approvals18,19

*Expanded indication or new formulation

22

DRUG NAMEMANUFACTURER

PROPOSEDINDICATION(S)

DRUG CLASSMECHANISM ROUTE UPCOMING EVENTS

Oncology

AbemaciclibEli Lilly

Breast cancer CDK 4/6 inhibitor Oral FDA decision in late 2016

BinimetinibArray/Novartis

Melanoma MEK inhibitor Oral FDA decision in late 2016

BrigatinibAriad

Non–small cell lung cancer ALK inhibitor Oral FDA decision in early 2017

BuparlisibNovartis

Breast cancer P13K Oral FDA decision in late 2016

Grastofil™ (filgrastim biosimilar)Apotex

Neutropenia Granulocyte colony-stimulating factor Subcutaneous, IV FDA decision in 2016

MidostaurinNovartis

Acute myeloid leukemia PKC inhibitor Oral FDA decision in mid-2016

Pegfilgrastim biosimilarSandoz

Same indications as reference product Leukocyte growth factor Subcutaneous FDA decision in 2016

RociletinibClovis

Non–small cell lung cancer EGFR inhibitor Oral FDA decision by June 28, 2016

Telotristat etiprateLexicon

Carcinoid syndrome Tryptophan hydroxylase inhibitor Oral FDA decision in late 2016

Rare Diseases

CSL-627CSL Behring

Hemophilia A Factor VIII IV FDA decision in late 2016

DeutetrabenazineAuspex

Chorea associated with Huntington’s disease Vesicular monoamine transporter 2 Oral FDA decision in mid-2016

EteplirsenSarepta

Duchenne muscular dystrophy mRNA inhibitor IV FDA decision by May 26, 2016

IGSC 20% Baxalta

Primary immunodeficiency Immune globulin IV FDA decision in late 2016

MP-104Marathon

Duchenne muscular dystrophy Glucocorticoid Oral FDA decision in early 2017

N9-GP/NN7999Neose

Hemophilia B Factor IX IV FDA decision by October 7, 2016

Obeticholic acidIntercept

Primary biliary cirrhosis Farnesoid X receptor agonist Oral FDA decision by May 29, 2016

Late Stage Pipeline Agents4


DRUG NAMEMANUFACTURER

PROPOSEDINDICATION(S)

DRUG CLASSMECHANISM ROUTE UPCOMING EVENTS

Rare Diseases

RI-002Adma

Primary immune deficiency disease Intravenous immune globulin IV FDA decision by September 30, 2016

Immunology and Multiple Sclerosis

ABP-501 adalimumab biosimilar

AmgenPsoriasis and rheumatoid arthritis TNF inhibitor Subcutaneous FDA decision possible in 2016

BaricitinibEli Lilly, Incyte

Rheumatoid arthritis JAK inhibitor Oral FDA decision in late 2016

BlisibimodAmgen

Lupus B-cell activating factor Subcutaneous FDA decision in late 2016

BrodalumabValeant, AstraZeneca

Psoriasis IL-17 inhibitor Subcutaneous FDA decision by November 16, 2016

CHS-1420Adalimumab biosimilar

CoherusPsoriasis TNF inhibitor Subcutaneous FDA decision possible in 2016

DaclizumabBiogen Idec, AbbVie

Multiple sclerosis IL-2 antagonist Subcutaneous FDA decision in Q2, 2016

Etanercept biosimilarSandoz

Same indications as Enbrel® TNF inhibitor Subcutaneous FDA decision possible in 2016

OcrelizumabGenentech, Roche

Multiple sclerosis CD20 antagonist IV FDA decision in late 2016

Remsima® (infliximab) biosimilarCelltrion

Same indications as Remicade® TNF blocker IV FDA decision possible in 2016

SarilumabSanofi, Regeneron

Rheumatoid arthritis IL-6 antagonist Subcutaneous FDA decision by October 30, 2016

Other

AbaloparatideRadius

Osteoporosis Bone resorption inhibitor Subcutaneous FDA decision in early 2017

Epoetin alfa biosimilarHospira

Anemia Erythropoiesis-stimulating agent (ESA) Subcutaneous, IV FDA decision possible in 2016

Velpatasvir; in combination with Sovaldi® (sofosbuvir)

GileadHepatitis C NS5A inhibitor Oral FDA decision by June 28, 2016

Late Stage Pipeline Agents4

24

DRUG NAMEMANUFACTURER CURRENT INDICATION PROPOSED EXPANDED

INDICATION(S) CURRENT DOSING UPCOMING EVENTS

CabozantinibExelixis

Thyroid cancer Renal cell carcinoma Oral FDA decision in mid-2016

Gilotrif® (afatinib)Boehringer-Ingelheim

Non-small cell lung cancer, EGFR exon 19 deletion or exon 21 substitution mutation Lung squamous cell carcinoma Oral FDA decision by

June 25, 2016

Viekira™ (ombitasvir + paritaprevir + ritonavir +

dasabuvir)AbbVie

Hepatitis C, genotype 1, including genotype 1b with compensated cirrhosis when used in

combination with ribavirin

Hepatitis C, genotype 1b with compensated cirrhosis without

ribavirinOral FDA decision by mid-2016

Lenvima® (lenvatinib)Eisai

Thyroid cancer Renal cell carcinoma Oral FDA decision by July 18, 2016

Revlimid® (lenalidomide) Celgene

Multiple myeloma, myelodysplastic syndromes (MDS) with a deletion 5q

abnormality, and mantle cell lymphoma

MDS with non-deletion 5q abnormality Oral FDA decision by mid-2016

Stelara® (ustekinumab)Janssen

Psoriasis, psoriatic arthritis Crohn’s disease Subcutaneous FDA decision by September 30, 2016

Stivarga® (regorafenib)Bayer

Colorectal cancer, gastrointestinal stromal tumor (GIST) Hepatocellular carcinoma Oral FDA decision in late 2016

Tenofovir alafenamideGilead

HIV as a component of combination regimens Hepatitis B Oral FDA decision by

October 15, 2016

New Indications + Formulations4


26

Glossary 1, 2

Accelerated Approval: Permits earlier approval of therapies developed for serious conditions with a currently unmet medical need; this designation may be based on surrogate endpoints, with post-marketing trials to verify clinical outcomes.

Adverse Event: Any undesirable experience associated with the use of a medical product in a patient.

Black Box Warning: Appears on the label of a prescription medication to alert the patient and healthcare provider about any important safety concerns, such as serious side effects or life-threatening risks.

Breakthrough Therapy: Provides for expedited development and review of drugs that treat serious or life-threatening conditions and demonstrate impressive preliminary clinical data; breakthrough designation holds the same advantages as fast track designation with the addition of intensive FDA guidance for efficient drug development.

Double-Blind Study: A clinical trial designed so that neither the participant nor the researcher knows if the treatment or a placebo has been administered.

Fast Track: Designed to increase patient access to critical drugs that treat serious conditions with a currently unmet medical need by facilitating a quick and efficient development and review process; many fast track medications also receive a priority review.

Orphan Drug Status: Granted to drugs and biologics which are intended to diagnose, prevent, or treat rare diseases and disorders that affect less than 200,000 people in the United States; a product with a greater target population may also qualify if the sponsor is not expected to recover its development and marketing costs.

Placebo-Controlled Studies: A study in which the effect of a drug is compared with the effect of a placebo (an inactive substance designed to resemble the drug).

Priority Review: Granted to drugs that are considered major therapeutic advancements or treat conditions currently lacking adequate therapy; this status shortens the goal for FDA review from ten to six months.

Randomized Study: A study design that randomly assigns participants into an experimental group or a control group. As the study is conducted, the only expected difference between the control and experimental groups in a randomized controlled trial (RCT) is the outcome variable being studied.

REMS: Risk Evaluation and Mitigation Strategy; strategy to manage known or potential serious risks associated with a drug or biologic product. REMS programs included medication guides, package inserts, and communication plans.


References

1. Fast track, accelerated approval and priority review. Food and Drug Administration Website. http://www.fda.gov/%20forconsumers/byaudience%20/%20forpatientadvocates/%20speedingaccesstoimportantnewtherapies/ucm128291.htm. Accessed December 20, 2013.

2. Developing products for rare disease & conditions. U.S. Food and Drug Administration (FDA) Website. http://www.fda.gov/%20ForIndustry/%20DevelopingProductsforRareDiseasesConditions/default.htm. Accessed December 20, 2013.

3. Frequently Asked Questions: Breakthrough Therapies. FDA Website. http://www.fda.gov/RegulatoryInformation/%20Legislation/FederalFoodDrugandCosmeticActFDCAct/%20SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed December, 2013.

4. BioPharm Insight. Boston, MA: Infinata; 2013. http://www.infinata.com/biopharma-solution/by-product/biopharm-insight.html. Accessed March and April 2016.5. Zepatier™ [package insert]. Whitehouse Station, NJ: Merck; 2016.6. Descovy® [package insert]. Foster City, CA: Gilead; 2016.7. Odefsey® [package insert]. Foster City, CA: Gilead; 2016.8. Taltz™ [package insert]. Indianapolis, IN: Eli Lilly and Company; 2016.9. Venclexta™ [package insert]. North Chicago, IL: AbbVie; 2016.10. Choueiri TK, Escudier B, Powles T, et al. Cabozantinib versus Everolimus in Advanced Renal-Cell Carcinoma. The New England Journal of Medicine. 2015;373:1814-23.11. Kappos L, Wiendl K, Selmaj DL, et al. Daclizumab HYP versus interferon beta-1a in relapsing multiple sclerosis. The New England Journal of Medicine. 2015 373:1418-28.12. Radke J. NDA for Huntington’s Drug Accepted by the FDA. Rare Disease Report Website. http://www.raredr.com/news/nda-huntington-drug-fda-teva. Accessed March 14, 2015.13. Intercept announces positive pivotal phase 3 POISE trial results. Intercept Website. http://ir.interceptpharma.com/releasedetail.cfm?releaseid=833072. Accessed March 23,

2016.14. Tucker ME. Obeticholic acid shows promise for primary biliary cirrhosis. Medscape Website. http://www.medscape.com/viewarticle/823669#vp_1. Accessed March 23, 2016.15. Inman S. FDA requests ODAC meeting for rociletinib following updated data. Targeted Oncology Website. http://www.targetedonc.com/news/fda-requests-odac-meeting-

rociletinib-updated-data. Accessed March 24, 2016.16. James D. FDA delays decision on new lung cancer drug. Specialty Pharmacy Times Website. http://www.specialtypharmacytimes.com/news/fda-delays-decision-on-new-lung-

cancer-drug. Accessed March 25, 2016.17. Gilead announces SVR12 rates from four phase 3 studies evaluating a once-daily, fixed-dose combination of sofobuvir (SOF) and velpatasvir (VEL) (GS-5816) for the treatment

of all six hepatitis genotypes. Gilead Website. http://www.gilead.com/news/press-releases/2015/9/gilead-announces-svr12-rates-from-four-phase-3-studies-evaluating-a-oncedaily-fixeddose-combination-of-sofosbuvir-sof-and-velpatasvir-vel-gs5816-for-the-treatment-of-all-six-hepatitis-c-genotypes. Accessed March 24, 2015.

18. New drug approvals. Drugs.com Website. http://www.drugs.com/newdrugs.html. Accessed March 24, 2016 and April 12, 2016.19. New indications & dosage forms for existing drugs. Drugs.com Website http://www.drugs.com/new-indications.html. Accessed March 24, 2016 and April 12, 2016.

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Documents

Q2 2016 Specialty Pipeline Report