Specialty Pipeline Report FIRST QUARTER 2017
FORWARD-LOOKING STATEMENTS 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. INDUSTRY AND MARKET DATA 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.
Table of Contents PREFACE.....................................................................................................................................5 RECENT APPROVALS................................................................................................................6
Rubraca™ (rucaparib).................................................................................................7
Vemlidy® (tenofovir alafenamide)..........................................................................8
TOP AGENTS TO ANTICIPATE...............................................................................................10 Abaloparatide...........................................................................................................11 Baricitinib.................................................................................................................. 12 Brodalumab............................................................................................................. 13 Deflazacort............................................................................................................... 14 Dupilumab................................................................................................................15
Ocrevus® (ocrelizumab)..........................................................................................16
Telotristat ethyl....................................................................................................... 17
RECENT SPECIALTY DRUG APPROVALS............................................................................19 LATE-STAGE AGENTS............................................................................................................ 20 NEW INDICATIONS, COMBINATIONS, AND FORMULATIONS....................................... 23 GLOSSARY............................................................................................................................... 25 REFERENCES........................................................................................................................... 26
AT D I P L O M AT, we blend clinical excellence with a personal touch— for happier lives and health that lasts.
Preface1,2,3 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 is pleased to provide you our Specialty Pipeline Report. This quarterly report, dedicated exclusively to specialty products, provides insight on 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 U.S. 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 3 trials or those for which new drug applications (NDAs) or biologic license applications (BLAs) have been filed with the FDA. This table includes products expected to have an FDA approval 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.
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 Therapy 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 months to six.
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 U.S. information is unavailable.
specialty pipeline report – Q1 2017
5
Recent Approvals
6
Rubraca™ (rucaparib)4,5
Recent Approvals APPROVAL DATE: Dec. 19, 2016 CLASS: PARP inhibitor HOW SUPPLIED: 200 and 300 mg tablets
INDICATION
DOSING
Treatment of patients with deleterious germline and/or somatic BRCA mutated advanced ovarian cancer who have previously been treated with two or more chemotherapies.
Administer 600 mg orally twice daily with or without food. Dosing adjustments may be made based on adverse reactions. Continue treatment until disease progression or unacceptable toxicity occurs.
CLINICAL TRIAL BRIEFING
SAFETY
Rucaparib was evaluated in two multicenter, single-arm, open-label studies composed of 106 total patients with BRCA+ ovarian cancer who had progressed after two or more previous chemotherapies. During the studies, patients received 600 mg of rucaparib orally twice daily as monotherapy until disease progression or unacceptable toxicity occurred. The endpoints measured in both studies were objective response rate (ORR) and duration of response (DOR) as assessed by the investigator and an independent radiology review using Response Evaluation Criteria in Solid Tumors (RECIST). Overall, ORR was 54% (95% CI: 44%, 64%) with 9% achieving complete response and 45% demonstrating a partial response. Median DOR was 9.2 months (95% CI: 6.6, 11.6). Rucaparib was approved under the FDA Accelerated Approval program based on ORR and DOR results. Continued approval may be dependent on confirmation of clinical benefit in additional trials.
Common Adverse Events: Nausea, fatigue (including asthenia), vomiting, anemia, abdominal pain, dysgeusia, constipation, decreased appetite, diarrhea, thrombocytopenia, and dyspnea Common Laboratory Abnormalities: Increased – Creatinine, ALT, AST, and cholesterol Decreased – Hemoglobin, lymphocytes, platelets, and absolute neutrophil count Serious Adverse Events: Myelodysplastic syndrome/acute myeloid leukemia (MDS/ AML) and embryo-fetal toxicity
OTHER AGENTS IN THERAPEUTIC AREA • Lynparza™ (olaparib)
Oncology
MANUFACTURER: Clovis Oncology STORAGE: 20–25°C (68–77°F) with
PATIENT POPULATION: 195,000 in the U.S.
excursions permitted from 15–30°C (59–86°F)
PROJECTED U.S. SALES (USDm)
400 300 200 100 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed Dec. 20, 2016
specialty pipeline report – Q1 2017
7
Vemlidy® (tenofovir alafenamide)4,6
Recent Approvals APPROVAL DATE: Nov. 10, 2016 CLASS: Nucleoside analog reverse
transcriptase inhibitor (NRTI)
Hepatitis
HOW SUPPLIED: 25 mg tablets MANUFACTURER: Gilead STORAGE: Store below 30°C (86°F); keep
PATIENT POPULATION: 850,000 to 2.2 million
container tightly closed; dispense in the original container
INDICATION
DOSING
Treatment of adult patients with chronic hepatitis B virus infection who have compensated liver disease.
Administer 25 mg orally once daily with food. Prior to the initiation of treatment, test patients for HIV infection. Tenofovir alafenamide should not be used as monotherapy for HIV. Assessment of serum creatinine, serum phosphorus, estimated creatinine clearance, urine glucose, and urine protein is recommended prior to starting therapy and should be monitored during
CLINICAL TRIAL BRIEFING
Tenofovir alafenamide was evaluated for the treatment of chronic hepatitis B infection in two randomized, doubleblind, active-controlled studies composed of 1,298 patients with compensated liver disease. The studies included a variety of patient types including those with genotypes B, C, and D, positive and negative HBeAg status, as well as treatment naïve and experienced patients. During the study patients received 25 mg of tenofovir alafenamide or 300 mg tenofovir disoproxil fumarate once daily for 48 weeks. The primary endpoint of both studies was the proportion of patients with plasma HBV DNA levels below 29 IU/mL at Week 48. The primary endpoint was achieved by 94% of the tenofovir alafenamide group and 93% of the tenofovir disoproxil fumarate group among HBeAg-negative patients corresponding to a treatment difference of 1.8% (95% CI: -3.6% to 7.2%). The primary endpoint was reached by 64% of the tenofovir alafenamide group and 67% of the tenofovir disoproxil fumarate group among HBeAg-positive patients corresponding to a treatment difference of -3.6% (95% CI: -9.8% to 2.6%).
8
OTHER AGENTS IN THERAPEUTIC AREA • Baraclude® (entecavir) • Epivir® (lamivudine) • Hepsera® (adefovir) • Tyzeka® (telbivudine) • Viread® (tenofovir disoproxil)
treatment as necessary. SAFETY
Common Adverse Events: Headache, abdominal pain, fatigue, cough, nausea, and back pain Serious Adverse Events: Renal impairment Boxed Warning: Lactic acidosis, severe hepatomegaly with steatosis, discontinuation of treatment may result in severe exacerbations of hepatitis B
PROJECTED SALES NOT AVAILABLE
specialty pipeline report – Q4 2016
9
Top Agents to Anticipate
10
Top Agents to Anticipate
Abaloparatide4,7,8
MANUFACTURER: Radius CLASS: Parathyroid hormone receptor
modulator ROUTE: Subcutaneous injection
CLINICAL TRIAL BRIEFING
SAFETY
Abaloparatide was evaluated for the treatment of postmenopausal osteoporosis in a multi-national, Phase 3, double-blind study composed of 2,463 female patients. Patients on study had a bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or a history of nonvertebral fracture within the past five years. During the study 80 µg of abaloparatide, 20 µg teriparatide, or placebo were administered daily by subcutaneous injection for 18 months. The primary endpoint of the study was the percentage of patients sustaining a new vertebral fracture in the abaloparatide vs placebo groups. New vertebral fractures occurred in 0.58% of the abaloparatide group, 4.22% of the placebo group, and 0.84% of the teriparatide group corresponding to a statistically significant risk difference of -3.64 (95% CI= -5.42, -2.10) for abaloparatide vs placebo. Additionally, BMD increase was greater for abaloparatide compared to placebo (p<0.001). An extension study of 1,139 patients receiving abaloparatide and 70 mg of alendronate is ongoing. After the first six months of this study, the abaloparatide/alendronate group demonstrated 87% reduction in new vertebral fracture (p<0.0001) and a 52% reduction in nonvertebral fractures (p=0.0122) compared to placebo.
The most commonly observed adverse events included hypercalciuria (11.3%), dizziness (10.0%), arthralgia (8.6%), back pain (8.5%), nausea (8.3%), and upper respiratory tract infection (8.3%).
Osteoporosis
ALIAS: PTH (1-34), ITM-058, BA-058, BIM-
44058
PATIENT POPULATION: 10 million in the U.S. CURRENT STATUS: FDA filing completed
TARGET INDICATION: Postmenopausal
osteoporosis
PROJECTED U.S. SALES (USDm)
UPCOMING EVENT
PDUFA – March 30, 2017 STATUS
None
400 300 200 100 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed Dec. 20, 2016
specialty pipeline report – Q1 2017
11
Top Agents to Anticipate
Baricitinib4,11,12,13
MANUFACTURER: Incyte and Eli Lilly CLASS: JAK 1 and 2 inhibitor ROUTE: Oral
Rheumatoid Arthritis
ALIAS: LY-3009104, INCB-28050,
PATIENT POPULATION: 1.5 million in the U.S. CURRENT STATUS: FDA filing completed
INCB-02850 TARGET INDICATION: Moderate-to-severe
rheumatoid arthritis (RA)
CLINICAL TRIAL BRIEFING
SAFETY
Baricitinib was evaluated for the treatment of moderate-to-severe RA in four randomized, double-blind, placebo-controlled Phase 3 clinical trials composed of 3,097 treatment naïve and experienced patients. During the trials patients received 2–4 mg of baricitinib orally once daily, 40 mg of Humira® (adalimumab) subcutaneously every two weeks, or placebo, and continued ongoing treatment with methotrexate (MTX) and/or a disease-modifying antirheumatic drug (DMARD) if applicable. The primary endpoint for the studies was American College of Rheumatology (ACR) 20 response after 12 or 24 weeks. In the RA-BEACON study, ACR20 response at Week 12 was 55% for bariticinib compared to 27% for placebo (p<0.001). Across all studies, baricitinib demonstrated a statistically significant improvement in ACR20 score compared to placebo, methotrexate, and adalimumab.
The most common adverse event observed in the RA-BEACON study was infections (minor and serious). Rare adverse events reported included herpes zoster, cancers (including nonmelanoma skin cancer), and major cardiovascular events.
12
PROJECTED GLOBAL SALES (USDm) 1500
UPCOMING EVENT
FDA decision delayed to April 2017 STATUS
None
1000 500 0
2017
2018
2019
USDm – US Dollars, millions Cortellis; Accessed Dec. 12, 2016
2020
2021
Top Agents to Anticipate
Brodalumab4,14,15
MANUFACTURER: Valeant CLASS: IL-17A antagonist ROUTE: Subcutaneous injection
Psoriasis
ALIAS: AMG-827, KHK-4827, MEDI-6365,
Lumicef, Siliq
PATIENT POPULATION: 7.5 million in the U.S. CURRENT STATUS: FDA filing completed
TARGET INDICATION: Moderate-to-severe
plaque psoriasis
CLINICAL TRIAL BRIEFING
Brodalumab was evaluated for the treatment of moderate-to-severe plaque psoriasis in three Phase 3, randomized, multi-center, double-blind, placebocontrolled trials that each included 12-week induction, 52-week maintenance, and long term extension segments. Patients received 140 or 210 mg of brodalumab, 45 or 90 mg of Stelara® (ustekinumab), or placebo. In certain studies, patients receiving brodalumab that weighed 100 kg or less received 140 mg and patients that weighed more than 100 kg received 210 mg (weight based). Brodalumab 140 mg was given every 2, 4, or 8 weeks and brodalumab 210 mg was administered once every 2 weeks. The primary endpoints for all studies were a 75% reduction in Psoriasis Area Severity Index (PASI 75) and achievement of static Physician’s Global Assessment (sPGA) scores of 0 or 1. In all trials, both 140 and 210 mg of brodalumab were superior to placebo as measured by PASI 75 and sPGA score of 0 or 1 (p<0.001) at Week 12. Brodalumab 210 mg and weight based dose were superior to ustekinumab (p<0.001) as measured by PASI 100 at Week 12. Across all three studies for patients given brodalumab, PASI 75 ranged from 60% to 86% and sPGA score of 0 or 1 ranged from 54% to 80%.
In July 2016, The FDA Advisory Committee voted unanimously in favor of approval for brodalumab as a treatment for adult patients with moderate-to-severe-plaque psoriasis. PROJECTED GLOBAL SALES (USDm)
SAFETY
The most common adverse events were headache and arthralgia. Other adverse events reported included fatigue, oropharyngeal pain, diarrhea, nausea, myalgia, influenza, injection site reactions, neutropenia, and tinea infections. Additionally, four completed suicides were committed by patients receiving brodalumab in the three pivotal psoriasis studies. UPCOMING EVENT
PDUFA – Feb. 17, 2017 STATUS
None
200 150 100 50 0
2017
2018
2019
2020
USDm – US Dollars, millions Cortellis; Accessed Dec. 12, 2016
specialty pipeline report – Q1 2017
13
Top Agents to Anticipate
Deflazacort4,16
MANUFACTURER: Marathon CLASS: Glucocorticoid ROUTE: Oral ALIAS: MP-104
CLINICAL TRIAL BRIEFING
SAFETY
Deflazacort was evaluated in a Phase 3, double-blind, randomized, placebo-controlled, multicenter study composed of 196 boys 5â&#x20AC;&#x201C;15 years of age with DMD. During the first phase of the study, patients received 0.9 mg/kg or 1.2 mg/kg of deflazacort, 0.75 mg/kg of prednisone, or placebo, daily for 12 weeks. In the second phase, patients receiving placebo were switched to deflazacort or prednisone and treatments continued for another 40 weeks. The primary endpoint was average change in muscle strength from baseline to Week 12 compared to placebo as measured by the Medical Research Council (MRC) scale. Deflazacort 0.9 mg/kg (0.25 vs -0.1, p=0.017), 1.2 mg/kg (0.36 vs -0.1, p=0.0003), and prednisone 0.75 mg/kg (0.37 vs -0.1, p=0.0002) all had statistically significant improvement in muscle strength compared to placebo. Additional analysis of change in muscle strength from weeks 12 to 52 resulted in further improvement in the deflazacort 0.9 mg/kg group compared to prednisone (0.29, p=0.044). The deflazacort 1.2 mg/ kg group did not achieve statistical significance (0.16, p=0.18).
The most common adverse events in patients given deflazacort or prednisone were Cushingoid appearance, erythema, hirsutism, weight gain, headache, and nasopharyngitis.
14
Rare Diseases
TARGET INDICATION: Duchenne muscular
CURRENT STATUS: FDA filing completed
dystrophy (DMD) PATIENT POPULATION: 1 in 5,000 male
births
UPCOMING EVENT
Expected FDA Decision â&#x20AC;&#x201C; February 2017 STATUS
Fast Track, Orphan, Priority Review, Rare Pediatric Disease
PROJECTED SALES NOT AVAILABLE
Top Agents to Anticipate
Dupilumab4,17,18
MANUFACTURER: Regeneron and Sanofi CLASS: IL-4 and -13 inhibitor ROUTE: Subcutaneous injection
Atopic Dermatitis
ALIAS: REGN-668, SAR-231893, duplimab,
dupixent
PATIENT POPULATION: 17.8 million in the U.S. CURRENT STATUS: FDA filing completed
TARGET INDICATION: Moderate-to-severe
atopic dermatitis
CLINICAL TRIAL BRIEFING
Dupilumab was evaluated for the treatment of moderate-to-severe atopic dermatitis in three randomized, placebocontrolled, Phase 3 studies composed of more than 2,500 total patients who experienced inadequate symptom control with topical corticosteroids (TCS). In all three studies the primary endpoint was the proportion of patients achieving a score of 0 or 1 (clear or almost clear) on the Investigator’s Global Assessment (IGA) and a reduction of 2 points or more in the score at Week 16 compared to baseline. An additional key secondary endpoint was a 75% reduction of Eczema Area and Severity Index (EASI-75) at Week 16. The SOLO 1 and SOLO 2 studies were identically designed. In both studies, patients received 300 mg of dupilumab or placebo weekly or alternating weeks of dupilumab and placebo. The primary endpoint was met by 36–38% of the two dupilumab groups and 8–10% of the placebo groups. EASI-75 was attained by 44–52% of dupilumab groups and 12–15% of placebo groups (p<0.001 for all comparisons of dupilumab to placebo).
The LIBERTY AD CHRONOS trial evaluated dupilumab in combination with TCS. Patients in this study received TCS in addition to 300 mg of dupilumab once per week, 300 mg of dupilumab every two weeks, or placebo, for 52 weeks. 39% of patients in the dupilumab groups achieved IGA score of 0 or 1 compared to 12% for placebo. EASI-75 was reached by 64–69% of patients receiving dupilumab compared to 23% for placebo (p<0.0001 for all comparisons of dupilumab to placebo). SAFETY
The most common adverse events in the SOLO trials included exacerbation of atopic dermatitis, injection site reactions, nasopharyngitis, and upper respiratory tract infection. UPCOMING EVENT
PDUFA – March 29, 2017
PROJECTED GLOBAL SALES (USDm) 4000 3000 2000 1000 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed Dec. 21, 2016
STATUS
Breakthrough, Priority Review
specialty pipeline report – Q1 2017
15
Top Agents to Anticipate
Ocrevus® (ocrelizumab)4,19,20
MANUFACTURER: Roche CLASS: Anti-CD-20 monoclonal antibody ROUTE: IV infusion
CLINICAL TRIAL BRIEFING
SAFETY
Ocrelizumab was evaluated for the treatment of RMS in two multicenter, randomized, double-blind, doubledummy, parallel-group trials composed of 1,656 total patients called OPERA I and OPERA II. During the studies, patients received 600 mg of ocrelizumab by IV infusion every six months or 44 mcg of Rebif® (interferon beta-1a) by subcutaneous injection three times weekly for 96 weeks. The primary endpoint was annualized relapse rate (ARR). ARR was reduced 46% (OPERA I) and 47% (OPERA II) in the ocrelizumab groups compared to interferon beta-1a (p<0.0001).
The most commonly observed adverse event in the OPERA trials was infusionrelated reactions.
Ocrelizumab was evaluated for PPMS in a randomized, double-blind, global multi-center study composed of 732 patients called ORATORIO. During the study patients received 600 mg of ocrelizumab by IV infusion every six months or placebo for at least 120 weeks and a predefined number of confirmed disability progression (CDP) events occurred. The primary endpoint was time to onset of 12-week CDP. Ocrelizumab reduced the relative risk of 12-week CDP by 24% compared to placebo (p=0.0321) and 24-week CDP was reduced by 25% (p=0.0365).
16
Multiple sclerosis
ALIAS: 2H7, R-1594, PRO-70769, RG-1594,
PR-070769, RO-4964913, Ocrevus TARGET INDICATIONS: Relapsing multiple sclerosis (RMS) and primary progressive multiple sclerosis (PPMS)
PATIENT POPULATION: 428,000 in the U.S. CURRENT STATUS: FDA filing completed
UPCOMING EVENT
PDUFA – March 28, 2017
PROJECTED GLOBAL SALES (USDm)
STATUS
Breakthrough, Priority Review
4000 3000 2000 1000 0
2017
2018
2019
USDm – US Dollars, millions Cortellis; Accessed Dec. 22, 2016
2020
2021
Top Agents to Anticipate
Telotristat Ethyl4,21,22
MANUFACTURER: Lexicon CLASS: Tryptophan hydroxylase inhibitor ROUTE: Oral
CLINICAL TRIAL BRIEFING
SAFETY
Telotristat ethyl was evaluated for the treatment of carcinoid syndrome in a Phase 3, randomized, placebo-controlled, parallel-group, multicenter, doubleblind study composed of 135 patients. During the study, patients received 250 mg or 500 mg of telotristat or placebo three times daily for 12 weeks while also receiving somatostatin analogue. After the initial 12 weeks of the study, an openlabel extension phase was conducted and patients received 500 mg of telotristat ethyl three times daily and somatostatin analogue.
The most commonly observed adverse events (>10% of telotristat patients) were nausea and diarrhea.
The primary endpoint of the initial phase of the study was reduction in number of daily bowel movements (DBMs). Both of the telotristat ethyl groups had a significant reduction in DBMs compared to placebo (-0.81 and -0.69 DBMs for the 250 mg and 500 mg groups compared to placebo, respectively, p<0.001). Reduction of 24-hour urinary 5-hydroxyindoleacetic acid (5-HIAA) from baseline was significantly reduced in both telotristat ethyl groups (-40.13 and -57.73 mg/24 hours for the 250 mg and 500 mg groups, respectively, p<0.001).
Oncology
ALIAS: Telotristat etiprate, telotristat
besylate, LP-778902, LX-1032, LX-1606, Xermelo TARGET INDICATION: Carcinoid syndrome
UPCOMING EVENT
PROJECTED U.S. SALES (USDm)
PDUFA – Feb. 28, 2017 STATUS
Fast track, Orphan, Priority Review
PATIENT POPULATION: <1 in 10,000 CURRENT STATUS: FDA filing completed
300 200 100 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed Dec. 23, 2016
specialty pipeline report – Q1 2017
17
18
Recent Specialty Drug Approvals23,24 DRUG NAME
APPROVED
DRUG CLASS MECHANISM
ROUTE
APPROVAL DATE
Adynovate® (antihemophilic factor recombinant, pegylated)*
Hemophilia A in pediatric patients
Factor VIII
IV
Dec. 22, 2016
Enbrel® (etanercept)*
Plaque psoriasis in pediatric patients 4 years of age and older
TNF inhibitor
Sub-Q
Nov. 4, 2016
Eucrisa™ (crisaborole)
Atopic dermatitis
PDE-4 inhibitor
Topical
Dec. 14, 2016
Rubraca™ (rucaparib)
Ovarian cancer with deleterious BRCA mutations
PARP inhibitor
Oral
Dec. 19, 2016
Selzentry® (maraviroc)*
HIV in pediatric patients 2 years of age and older
CCR-5 co-receptor antagonist
Oral
Nov. 4, 2016
Spinraza™ (nusinersen)
Spinal muscular atrophy
SMN2-directed antisense oligonucleotide
Intrathecal injection
Dec. 23, 2016
Vemlidy® (tenofovir alafenamide)
Hepatitis B
NRTI
Oral
Nov. 10, 2016
*Expanded indication or new formulation
specialty pipeline report – Q1 2017
19
Late-Stage Pipeline Agents4 DRUG NAME MANUFACTURER
PROPOSED INDICATION(S)
DRUG CLASS MECHANISM
ROUTE
UPCOMING EVENTS
Binimetinib Array
Melanoma, NRAS+
MEK inhibitor
Oral
PDUFA – June 30, 2017
Brigatinib Ariad
Non-small-cell lung cancer, ALK+
ALK inhibitor
Oral
PDUFA – April 29, 2017
Duvelisib Verastem
Chronic lymphocytic leukemia
PI3K inhibitor
Oral
FDA decision in late 2017
Enasidenib Agios, Celgene
Acute myeloid leukemia (AML), IDH2+
IDH-2 inhibitor
Oral
FDA decision in mid-to-late 2017
Gilteritinib Astellas
AML, FLT3+
FLT3 TKI
Oral
FDA decision in late 2017
Midostaurin Novartis
AML, FLT3+
FLT3 TKI
Oral
FDA decision in early-to-mid 2017
Neratinib Puma
Breast cancer, HER2+
TKI
Oral
FDA decision in mid-2017
Niraparib Tesaro, Janssen
Ovarian cancer
PARP inhibitor
Oral
PDUFA – June 30, 2017
Pegfilgrastim biosimilar Sandoz
Same indications as Neulasta®
Leukocyte growth factor
Sub-Q
Manufacturer addressing complete response letter
Pegfilgrastim biosimilar CHS-1701 Coherus
Same indications as Neulasta®
Leukocyte growth factor
Sub-Q
PDUFA – June 9, 2017
Ribociclib Novartis
Breast cancer, HR+, HER2-
CDK 4/6 inhibitor
Oral
FDA decision in early 2017
Telotristat ethyl Lexicon, Ipsen
Carcinoid syndrome
Tryptophan-5 hydroxylase inhibitor
Oral
PDUFA – Feb. 28, 2017
Cerliponase alfa Biomarin
CLN2 Batten disease
Tripeptidyl peptidase 1
IV
PDUFA – April 27, 2017
Deflazacort Marathon
Duchenne muscular dystrophy
Corticosteroid
Oral
FDA decision in February 2017
Deutetrabenazine Teva
Huntington’s disease
VMAT 2 inhibitor
Oral
PDUFA – April 3, 2017
Edaravone Mitsubishi Tanabe
Amyotrophic lateral sclerosis (ALS)
Antioxidant agent, free radical scavenger, neuroprotectant
IV
FDA decision in mid-2017
Hemophilia B
Factor IX
IV
FDA decision in early 2017
Oncology
Rare Diseases
N9-GP/NN7999 Novo Nordisk
20
Late-Stage Pipeline Agents4 DRUG NAME MANUFACTURER
PROPOSED INDICATION(S)
DRUG CLASS MECHANISM
ROUTE
UPCOMING EVENTS
Pegvaliase Biomarin
Phenylketonuria (PKU)
Enzyme replacement
Sub-Q
FDA decision in late 2017
Plasminogen Prometic
Hypoplasminogenemia
Plasminogen replacement
IV
FDA decision in mid-to-late 2017
Valbenazine Neurocrine Biosciences
Tardive dyskinesia
VMAT 2 inhibitor
Oral
PDUFA – April 11, 2017
Adalimumab biosimilar CHS-1420 Coherus
Same indications as Humira®
TNF blocker
Sub-Q
FDA decision in mid-to-late 2017; delayed product launch likely
Adalimumab biosimilar M923 Momenta
Same indications as Humira®
TNF blocker
Sub-Q
FDA decision in late 2017; delayed product launch likely
Baricitinib Eli Lilly, Incyte
Rheumatoid arthritis
JAK 1/2 inhibitor
Oral
FDA decision in April 2017
Brodalumab Valeant
Psoriasis
IL-17 inhibitor
Sub-Q
PDUFA – Feb. 17, 2017
Dimethyl fumarate Almirall
Psoriasis
Unknown
Oral
FDA decision in mid-to-late 2017
Guselkumab Janssen, Morphosys
Psoriasis
IL-23 inhibitor
Sub-Q
FDA decision in late 2017
Infliximab biosimilar SB2 Samsung Bioepis, Merck
Same indications as Remicade®
TNF blocker
IV
FDA decision in early 2017
IVIG-SN (human normal immunoglobulin G) Green Cross
Primary immunodeficiency disease
Immune globulin
IV
Manufacturer addressing complete response letter
Ocrelizumab Roche
Multiple sclerosis
CD20 antagonist
IV
PDUFA – March 28, 2017
Sarilumab Sanofi, Regeneron
Rheumatoid arthritis
IL-6 antagonist
Sub-Q
Manufacturer addressing complete response letter
Sirukumab GlaxoSmithKline, Janssen
Rheumatoid arthritis
IL-6 antagonist
Sub-Q
FDA decision in mid-to-late 2017
Abaloparatide Radius
Osteoporosis
Parathyroid hormone-related protein analog
Sub-Q
PDUFA – March 30, 2017
Dupilumab Sanofi, Regeneron
Atopic dermatitis (eczema)
IL-4 blocker
Sub-Q
PDUFA – March 29, 2017
Immunology and Multiple Sclerosis
Other
specialty pipeline report – Q1 2017
21
Late-Stage Pipeline Agents4 DRUG NAME MANUFACTURER
PROPOSED INDICATION(S)
DRUG CLASS MECHANISM
ROUTE
UPCOMING EVENTS
Glecaprevir + pibrentasvir AbbVie
Hepatitis C, pangenotypic
NS3/4A protease inhibitor + NS5A inhibitor
Oral
FDA decision in mid-to-late 2017
Ibalizumab TaiMed, Theratechnologies
HIV
HIV-1 entry inhibitor
IV
FDA decision in mid-2017
Romosozumab Amgen, UCB
Osteoporosis
Sclerostin inhibitor
Sub-Q
PDUFA â&#x20AC;&#x201C; July 19, 2017
Voxilaprevir + sofosbuvir + velpatasvir Gilead
Hepatitis C, all genotypes
NS3 protease inhibitor + NS5B polymerase inhibitor + NS5A inhibitor
Oral
FDA decision in mid-late 2017
22
New Indications, Combinations, and Formulations4 DRUG NAME MANUFACTURER
CURRENT INDICATION
PROPOSED EXPANDED INDICATION(S)
CURRENT DOSING
UPCOMING EVENTS
Benlysta® (belimumab) GlaxoSmithKline
Lupus
Lupus – new formulation
Sub-Q
FDA decision in mid-2017
Berinert® (C1 esterase inhibitor, human) CSL Behring
Hereditary angioedema
Hereditary angioedema – new formulation
Sub-Q
FDA decision in early 2017
Imbruvica® (ibrutinib) AbbVie, Janssen
Mantle cell lymphoma (MCL), chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with or without 17p deletion, Waldenstrom’s macroglobulinemia
Marginal zone lymphoma
Oral
FDA decision in early 2017
Nitisinone Cycle
Hereditary tyrosinemia type 1
Hereditary tyrosinemia type 1 – new formulation
Oral
FDA decision in mid-2017
Orencia® (abatacept) Bristol-Myers Squibb
Adult rheumatoid arthritis, juvenile idiopathic arthritis
Psoriatic arthritis
Sub-Q
FDA decision in mid-to-late 2017
Praluent® (alirocumab) Sanofi, Regeneron
Hypercholesterolemia
Hypercholesterolemia – once monthly dose formulation
Sub-Q
PDUFA – Jan. 24, 2017
Revlimid® (lenalidomide) Celgene
Multiple myeloma (MM), myelodysplastic syndromes, Mantle cell lymphoma
MM as maintenance therapy after stem-cell transplant
Oral
PDUFA – Feb. 24, 2017
Stivarga® (regorafenib) Bayer
Colorectal cancer, gastrointestinal stromal tumors (GIST)
Hepatocellular carcinoma
Oral
FDA decision in mid-2017
Tafinlar® (dabrafenib) + Mekinist® (trametinib) Novartis
Melanoma, BRAF+
Non-small-cell lung cancer, BRAF+
Oral
FDA decision in early 2017
TLE-400 Mylan
HIV
Combination antiretroviral treatment
Oral
FDA decision in early-to-mid 2017
specialty pipeline report – Q1 2017
23
24
Glossary1, 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 postmarketing 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 Therapy 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 whether 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 those used to treat conditions currently lacking adequate therapy; this status shortens the goal for FDA review from 10 months to six. 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) — A 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.
specialty pipeline report – Q1 2017
25
References
26
1.
Fast track, accelerated approval and priority review. Food and Drug Administration Website. fda.gov/%20forconsumers/byaudience%20/%20 forpatientadvocates/%20speedingaccesstoimportantnewtherapies/ucm128291.htm. Accessed Dec. 20, 2013.
2.
Developing products for rare disease & conditions. U.S. Food and Drug Administration (FDA) Website. fda.gov/%20ForIndustry/%2 DevelopingProductsforRareDiseasesConditions/default.htm. Accessed Dec. 20, 2013.
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Frequently Asked Questions: Breakthrough Therapies. FDA Website. fda.gov/RegulatoryInformation/%20Legislation/ FederalFoodDrugandCosmeticActFDCAct/%20SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed December 2013.
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Cortellis™. Thomson Reuters; cortellis.thomsonreuterslifesciences.com/ngg/login.do. Accessed Dec. 2016.
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Rubraca™ [package insert]. Boulder, CO: Clovis Oncology. 2016.
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Vemlidy® [package insert]. Foster City, CA: Gilead. 2016.
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Miller PD, Hattersley G, and Riis BJ. Effect of abaloparatide vs. placebo on new vertebral fractures in postmenopausal women with osteoporosis. JAMA. 2016;316(7):722-733.
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Radius announces positive top-line data from ACTIVExtend trial including combined 25-month results. Radius Website. investors.radiuspharm.com/ releasedetail.cfm?releaseid=918453. Accessed Dec. 20, 2016.
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Baricitinib demonstrates superiority to adalimumab in improving signs and symptoms of rheumatoid arthritis in pivotal Phase 3 study. Eli Lilly Website. investor.lilly.com/releasedetail.cfm?ReleaseID=936515. Accessed Sept. 14, 2016.
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Lilly and Incyte announce positive top-line results from Phase 3 trial of baricitinib in moderate to severe rheumatoid arthritis. Eli Lilly Website. investor.lilly. com/releaseDetail.cfm?ReleaseID=886732. Accessed Sept. 14, 2016.
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Baricitinib superior to placebo in reducing rheumatoid arthritis disease activity in second Phase 3 study. Eli Lilly Website. investor.lilly.com/releasedetail. cfm?ReleaseID=897566. Accessed Sept. 14, 2016.
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Baricitinib superior to methotrexate in reducing signs and symptoms in pivotal Phase 3 study in patients with rheumatoid arthritis. Eli Lilly Website. lillymedia. com/releasedetail.cfm?ReleaseID=934142. Accessed Sept. 14, 2016.
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Genovese MC, Kremer J, Zamani O, et al. Baricitinib in Patients with Refractory Rheumatoid Arthritis. N Engl J Med. 2016;374:1243-52.
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FDA advisory committee recommends approval of brodalumab for treatment of moderate-to-severe plaque psoriasis. Valeant Website. ir.valeant.com/newsreleases/2016/07-19-2016-212752481. Accessed Sept. 12, 2016.
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FDA Briefing Document: Dermatologic and Ophthalmic Drugs Advisory Committee Meeting, July 19, 2016. Background Package for BLA 761032 Siliq (brodalumab) injection, 210 mg/1.5 mL.
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Griggs RC, Miller JP, Greenberg CR, et al. Efficacy and safety of deflazacort vs prednisone and placebo for Duchenne muscular dystrophy. American Academy of Neurology. Published ahead of print on Aug. 26, 2016 as 10.1212/WNL.0000000000003217.
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Simpson EL, Bieber T, Guttman-Yassky E, et al. Two Phase 3 trials of dupilumab versus placebo in atopic dermatitis. N Engl J Med 2016;375:2335-48.
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Regeneron and Sanofi announce that dupilumab used with topical corticosteroid (TCS) was superior to treatment with TCS alone in long-term Phase 3 trial in inadequately controlled moderate-to-severe atopic dermatitis patients. Regeneron Website. investor.regeneron.com/releasedetail.cfm?releaseid=974316. Accessed Dec. 22, 2016.
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Roche’s ocrelizumab first investigational medicine to show positive pivotal study results in both relapsing and primary progressive forms of multiple sclerosis. Roche Website. roche.com/media/store/releases/med-cor-2015-10-08.htm. Accessed Dec. 22, 2016.
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Montalban X, Hemmer B, Giovannoni G, et al. Efficacy and safety of ocrelizumab in primary progressive multiple sclerosis: results of the Phase 3 doubleblind, placebo-controlled ORATORIO study. Neurology April 5, 2016 vol. 86 no. 16 Supplement S49.001.
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Lapuerta P, Zambrowicz B, Fleming D et al. Telotristat etiprate, a novel inhibitor of serotonin synthesis for the treatment of carcinoid syndrome. Clin. Invest. (Lond.) (2015) 5(5), 447–456.
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New drug approvals. Drugs.com Website. drugs.com/newdrugs.html. Accessed Dec. 29, 2016.
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New indications & dosage forms for existing drugs. Drugs.com Website drugs.com/new-indications.html. Accessed Dec. 29, 2016.
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