Specialty Pipeline Report 2ND 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, 2016, 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
Siliq™ (brodalumab)...................................................................................................7
Emflaza™ (deflazacort)..............................................................................................8
Austedo™ (deutetrabenazine)..................................................................................9
Dupixent® (dupilumab)...........................................................................................10
Zejula™ (niraparib)....................................................................................................11
Ocrevus™ (ocrelizumab).......................................................................................... 12
Kisqali® (ribociclib).................................................................................................. 13
Xermelo™ (telotristat ethyl).................................................................................... 14
TOP AGENTS TO ANTICIPATE...............................................................................................16 Brigatinib.................................................................................................................. 17
Cerliponase alfa......................................................................................................18
Edaravone................................................................................................................19 Midostaurin............................................................................................................. 20
Nonacog beta pegol...............................................................................................21
Valbenazine............................................................................................................ 22 RECENT SPECIALTY DRUG APPROVALS........................................................................... 25 LATE-STAGE PIPELINE AGENTS........................................................................................... 26 NEW INDICATIONS, COMBINATIONS, AND FORMULATIONS....................................... 28 GLOSSARY............................................................................................................................... 30 REFERENCES............................................................................................................................ 31
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 – Q2 2017
5
Recent Approvals
6
Siliq™ (brodalumab)4,5
Recent Approvals APPROVAL DATE: Feb. 15, 2017 CLASS: Interleukin-17 receptor A (IL-17RA)
antagonist HOW SUPPLIED: 210 mg/1.5 mL prefilled
syringe for single-dose
INDICATION
Treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed or no longer respond to other systemic therapies. CLINICAL TRIAL BRIEFING
Brodalumab was evaluated for the treatment of moderate-to-severe plaque psoriasis in three multi-center, randomized, double-blind, controlled trials composed of 4,373 total patients. Patients on study had at least a six-month history of moderate-to-severe plaque psoriasis and were considered candidates for systemic therapy or phototherapy. During the study brodalumab or placebo were given at weeks 0, 1, and 2, then every two weeks thereafter through Week 12. Additionally, in selected trials certain patients received 45 or 90 mg of Stelara® (ustekinumab) (weight-based dosing), on weeks 0, 4, and 16, and then every 12 weeks thereafter. The primary endpoint for all studies was the proportion of patients achieving ≥75% reduction in Psoriasis Area and Severity Index (PASI) score and Static Physician’s Global Assessment (sPGA) of 0 or 1, and at least a two-point improvement from baseline at Week 12. Across all three trials PASI 75 ranged from 83 to 86% for the brodalumab groups, 3 to 8% for placebo, and 70 to 85% for ustekinumab. sPGA of 0 or 1 ranged from 76 to 80% for brodalumab, 1 to 4%
for placebo, and 57 to 61% for ustekinumab. A continuation period was conducted through 52 weeks with patients receiving brodalumab or placebo every two weeks. 79–83% of brodalumab patients maintained sPGA response score of 0 or 1, and 87% maintained PASI 75 response. 72% of PASI 100 responders at Week 12 maintained that response at Week 52.
Psoriasis
MANUFACTURER: Valeant STORAGE: 2–8°C (36–46°F) in the original
carton; protect from light; may be stored up to a maximum of 25°C (77°F) for up to 14 days; do not freeze or shake
the U.S.
OTHER AGENTS IN THERAPEUTIC AREA
• Cimzia® (certolizumab pegol) • Cosentyx® (secukinumab) • Enbrel® (etanercept) • Humira® (adalimumab) • Otezla® (apremilast) • Remicade® (infliximab) • Simponi® (golimumab)
DOSING
• Stelara® (ustekinumab)
Administer 210 mg by subcutaneous injection on weeks 0, 1, and 2, then every two weeks thereafter.
• Taltz® (ixekizumab)
PROJECTED GLOBAL SALES (USDm)
SAFETY
Common Adverse Events: (incidence ≥1%) arthralgia, headache, fatigue, diarrhea, oropharyngeal pain, nausea, myalgia, injection site reactions, influenza, neutropenia, and tinea infections Warnings and Precautions: Infections, tuberculosis, Crohn’s disease, interaction with live vaccines Boxed Warning: Suicidal ideation and behavior, including completed suicides in clinical trials, monitor patients with suicidal thoughts or behavior and refer to mental health professionals as appropriate; brodalumab is available only through a Risk Evaluation and Mitigation Strategies (REMS) program
PATIENT POPULATION: 7.5 million patients in
200 150 100 50 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
Specialty Pipeline Report – Q2 2017
7
Emflaza™ (deflazacort)4,6
Recent Approvals APPROVAL DATE: Feb. 9, 2017 CLASS: Corticosteroid HOW SUPPLIED: 6, 18, 30, and 36 mg
tablets; 22.75 mg/mL oral solution MANUFACTURER: PTC
INDICATION
DOSING
Treatment of Duchenne muscular dystrophy (DMD) in patients 5 years of age and older.
Administer 0.9 mg/kg/day once daily for both tablet and oral suspension formulations.
CLINICAL TRIAL BRIEFING
SAFETY
Deflazacort was evaluated in two randomized, double-blind, placebocontrolled trials composed of 225 total male patients ranging from 5 to 15 years of age with DMD who had abnormal dystrophin or confirmed mutation of the dystrophin gene. In Study 1, patients received 0.9 or 1.2 mg/kg/day of deflazacort, an active comparator, or placebo for 52 weeks. The primary endpoint was change in average muscle strength score between baseline and Week 12 as evaluated by the modified Medical Research Council 11-point scale. Deflazacort 0.9 mg/kg/day demonstrated a 0.15 change from baseline compared to a -0.10 change for placebo (p=0.017) as determined by least squares (LS) mean. Deflazacort 1.2 mg/kg/day had a higher incidence of adverse reactions and is not recommended. Study 2 was 104 weeks in duration and compared deflazacort to placebo by measuring average muscle strength score on a 0–5 scale. However, no statistically significant difference was found.
Common Adverse Events: (≥10% for deflazacort and greater than placebo) Cushingoid appearance, weight increase, appetite decrease, upper respiratory tract infection, cough, pollakiuria, hirsutism, central obesity, and nasopharyngitis Warnings and Precautions: Altered endocrine function, immunosuppression and increased risk of infection, altered cardiovascular and renal function, gastrointestinal perforation, behavioral and mood disturbances, bone effects, ophthalmic effects, vaccination limitations, and serious skin rashes
8
OTHER AGENTS IN THERAPEUTIC AREA
• Exondys 51™ (eteplirsen)
Rare Diseases
STORAGE: 20–25°C (68–77°F) with
excursions permitted between 15 and 30°C (59–86°F) PATIENT POPULATION: 1 in every 7,250 males aged 5–24 years
PROJECTED SALES NOT AVAILABLE
Recent Approvals
Austedo ™ (deutetrabenazine)4,7
APPROVAL DATE: April 3, 2017 CLASS: VMAT2 inhibitor HOW SUPPLIED: 6, 9, and 12 mg tablets MANUFACTURER: Teva
Treatment of chorea associated with Huntington’s disease.
from tetrabenazine to deutetrabenazine, see the prescribing information for details on dosage conversion.
CLINICAL TRIAL BRIEFING
SAFETY
Deutetrabenazine was evaluated in a randomized, double-blind, placebocontrolled, multi-center trial composed of 90 patients with chorea associated with Huntington’s disease. During the study patients received deutetrabenazine at an initial dose of 6 mg/day then increased as necessary to a maximum of 48 mg/day until chorea was adequately controlled or intolerable adverse events occurred. The mean dose after titration was 40 mg/ day. Additional patients received placebo. The administration period was 12 weeks and included a titration segment of eight weeks and a maintenance segment of four weeks. The primary endpoint of the study was Total Maximal Chorea Score (TMCS), a component of the Unified Huntington’s Disease Rating Scale. The change in TMCS was -4.4 for the deutetrabenazine group and -1.9 for placebo (p<0.001).
Common Adverse Events: (>8% of deutetrabenazine patients and greater than placebo) somnolence, diarrhea, dry mouth, and fatigue Warnings and Precautions: Neuroleptic malignant syndrome, akathisia, agitation, restlessness, parkinsonism, and sedation/ somnolence Boxed Warning: Increased risk of depression and suicidal thoughts, weigh potential benefits and risks of deutetrabenazine administration accordingly and monitor patients as needed
INDICATION
OTHER AGENTS IN THERAPEUTIC AREA
• Xenazine® (tetrabenazine)
Rare Diseases
STORAGE: 25°C (77°F) with excursions
permitted from 15 to 30°C (59–86°F); protect from light and moisture PATIENT POPULATION: 30,000 patients in the U.S. (Huntington’s disease)
PROJECTED U.S SALES (USDm) 600 400 200 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
DOSING
Take orally at an initial dose of 6 mg once daily. Increase as necessary by 6 mg at weekly intervals to a tolerable dose that reduces chorea, up to a maximum of 48 mg daily (taken as 24 mg twice daily). If the daily dose is ≥12 mg, divide into two doses. Take deutetrabenazine with food and swallow tablets whole. If switching Specialty Pipeline Report – Q2 2017
9
Dupixent® (dupilumab)4,8
Recent Approvals APPROVAL DATE: March 28, 2017 CLASS: IL-4 receptor alpha antagonist HOW SUPPLIED: 300 mg/2 mL pre-filled
syringes MANUFACTURER: Regeneron and Sanofi-
Atopic Dermatitis
STORAGE: 2–8°C (36–46°F) in the original
PATIENT POPULATION: 300,000 patients in
carton; protect from light; may be stored up to a maximum of 25°C (77°F) for up to 14 days; do not freeze, shake, or expose to heat
the U.S. have moderate-to-severe atopic dermatitis
Aventis
INDICATION
Treatment of adult patients with moderate-to-severe atopic dermatitis (AD) with disease not adequately controlled by topical prescription treatments or for those who are not good candidates for these treatments. CLINICAL TRIAL BRIEFING
Dupilumab was evaluated in three randomized, double-blind, placebocontrolled trials composed of 2,119 total patients with moderate-to-severe AD that was not adequately controlled by topical treatments. In all three trials patients received dupilumab 600 mg at Week 0 then 300 mg every other week thereafter. Additional patients received placebo. In the two dupilumab monotherapy trials, administration continued for 16 weeks. In the third study, concomitant topical corticosteroids (TCS) and, if necessary, topical calcineurin inhibitors were given in addition to dupilumab or placebo for 52 weeks. The primary endpoint in all three trials was the proportion of patients achieving an Investigator’s Global Assessment (IGA) score of 0 (clear) or 1 (almost clear) and at least a two-point improvement from baseline to Week 16. Across the three trials, IGA 0 or 1 score was achieved by 36–39% of the dupilumab groups compared to 9–12% of the placebo ± TCS groups. Additionally, Eczema Area and Severity Score improvement of ≥75% (EASI-75) was 10
evaluated and ranged from 44 to 69% in the dupilumab groups compared to 12–23% in the placebo ± TCS groups. DOSING
Administer by subcutaneous injection at an initial dose of 600 mg (given as two 300 mg injections at different locations), then 300 mg every other week thereafter. SAFETY
Common Adverse Events: (incidence ≥1%) injection site reactions, conjunctivitis, blepharitis, oral herpes, keratitis, eye pruritis, other herpes simplex viral infections, and dry eye Warnings and Precautions: Hypersensitivity, conjunctivitis and keratitis, and comorbid asthma OTHER AGENTS IN THERAPEUTIC AREA
• Eucrisa™ (crisaborole)
PROJECTED GLOBAL SALES (USDm) 3000 2000 1000 0
2017
2018
2019
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
2020
2021
Recent Approvals
Zejula™ (niraparib)4,9
APPROVAL DATE: March 27, 2017 CLASS: PARP inhibitor HOW SUPPLIED: 100 mg capsules MANUFACTURER: Tesaro
INDICATION
DOSING
Maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.
Administer 300 mg orally once daily at approximately the same time every day with or without food. Initiate niraparib no later than eight weeks after the last administration of a treatment that contains platinum.
Oncology
STORAGE: 20–25°C (68–77°F) with
excursions permitted between 15 and 30°C (59–86°F) PATIENT POPULATION: 196,000 patients in the U.S. (ovarian cancer)
PROJECTED U.S SALES (USDm)
CLINICAL TRIAL BRIEFING
Niraparib was evaluated in a doubleblind, placebo-controlled clinical trial composed of 553 patients with recurrent platinum-sensitive epithelial ovarian, fallopian tube, or primary peritoneal cancer. During the study, patients received 300 mg of niraparib or placebo daily until disease progression or intolerable adverse events occurred. Patients on study had previously received at least two prior platinum-containing regimens and responded to the most recent regimen. Patients with or without BRCA genetic mutations were included. The primary endpoint was progressionfree survival (PFS) as determined by central independent assessment using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 or other criteria as necessary. For patients with BRCA mutation, PFS for the niraparib group was 21.0 months (95% CI: 12.9, not reached) compared to 5.5 months (95% CI: 3.8, 7.2) for placebo. For patients without BRCA mutation PFS was 9.3 months (95% CI: 7.2, 11.2) for the niraparib group and 3.9 months (95% CI: 3.7, 5.5) for placebo (p<0.0001 for both comparisons).
SAFETY
Common Adverse Events: (incidence ≥10%) thrombocytopenia, anemia, neutropenia, leukopenia, palpitations, nausea, constipation, vomiting, abdominal pain/ distension, mucositis/stomatitis, diarrhea, dyspepsia, dry mouth, fatigue/asthenia, decreased appetite, urinary tract infection, AST/ALT elevation, myalgia, back pain, arthralgia, headache, dizziness, dysgeusia, insomnia, anxiety, nasopharyngitis, dyspnea, cough, rash, and hypertension Warnings and Precautions: Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML), bone marrow suppression, cardiovascular effects, and embryo-fetal toxicity
600 400 200 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
OTHER AGENTS IN THERAPEUTIC AREA
• Lynparza® (olaparib) • Rubraca® (rucabarib)
Specialty Pipeline Report – Q2 2017
11
Ocrevus™ (ocrelizumab)4,10
APPROVAL DATE: March 28, 2017 CLASS: CD20-directed cytolytic antibody HOW SUPPLIED: 300 mg/10 mL (30 mg/mL)
single dose vials MANUFACTURER: Genentech
INDICATION
Treatment of patients with relapsing or primary progressive forms of multiple sclerosis (MS). CLINICAL TRIAL BRIEFING
Ocrelizumab was evaluated for the treatment of relapsing forms of multiple sclerosis (RMS) in two randomized, double-blind, double-dummy, active comparator-controlled, identically designed clinical trials composed of 827 total patients. After an initial titration period, patients received ocrelizumab 600 mg or placebo by IV injection every 24 weeks or Rebif® (interferon beta-1a) 44 mcg by subcutaneous injection three times per week for 96 weeks. The primary endpoint of both studies was annualized relapse rate (ARR). For the ocrelizumab groups, ARR was 0.155 and 0.156 compared to 0.290 and 0.292 for the interferon beta-1a groups, corresponding to a relative reduction of 46–47% (p<0.0001). A third study evaluated ocrelizumab in a randomized, double-blind, placebocontrolled clinical trial composed of 488 patients with primary progressive MS (PPMS). Patients received ocrelizumab 600 mg or placebo every 24 weeks for 120 weeks. The primary endpoint of this study was the proportion of patients with 12-week confirmed disability progression defined as an increase of ≥1.0 from the 12
Multiple Sclerosis
Recent Approvals
baseline in Expanded Disability Status Scale (EDSS) score for patients with a baseline score of ≤5.5 or a score increase of ≥0.5 when the baseline score was >5.5. 32.9% of the ocrelizumab group and 39.3% of the placebo group demonstrated 12-week confirmed disability progression, corresponding to a risk reduction of 24% (p=0.0321). DOSING
Before the initial administration, screen patients for hepatitis B infection. Before each administration, pre-medicate with methylprednisolone (or other equivalent corticosteroid) and an antihistamine. Administer ocrelizumab by intravenous infusion. The starting dose is 300 mg followed by an additional 300 mg two weeks later. For subsequent doses, administer 600 mg every six months.
STORAGE: 2–8°C (36–46°F); keep in the
original carton to protect from light; do not freeze or shake PATIENT POPULATION: Relapsing MS – 340,000; Primary progressive MS – 40,000 (in the U.S.)
OTHER AGENTS IN THERAPEUTIC AREA
RMS • Aubagio® (teriflunomide) • Avonex® (interferon beta-1a) • Betaseron® (interferon beta-1b) • Copaxone® (glatiramer acetate) • Extavia® (interferon-beta 1b) • Gilenya® (fingolimod) • Glatopa® (glatiramer acetate) • Lemtrada® (alemtuzumab) • Plegridy® (pegylated interferon-beta 1a) • Rebif® (interferon beta-1a) • Tecfidera® (dimethyl fumarate) • Tysabri® (natalizumab) • Zinbryta® (daclizumab) PPMS • None
PROJECTED GLOBAL SALES (USDm)
SAFETY
Common Adverse Events: RMS: (incidence ≥10% and >interferon beta 1-a) upper respiratory tract infections and infusion reactions. PPMS: (incidence ≥10% and >placebo) upper respiratory tract infections, infusion reactions, skin infections, and lower respiratory tract infections. Warnings and Precautions: Infusion reactions, infections, and malignancies
4000
2000 0
2017
2018
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
2019
2020
2021
Recent Approvals
Kisqali® (ribociclib)4,11
APPROVAL DATE: March 13, 2017 CLASS: Kinase inhibitor HOW SUPPLIED: 200 mg tablets MANUFACTURER: Novartis
Oncology
STORAGE: 20–25°C (68–77°F); store in the
original package PATIENT POPULATION: 1 million in the U.S.
INDICATION
Treatment of hormone receptor (HR)positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in postmenopausal women when used in combination with an aromatase inhibitor as an initial endocrine-based therapy. CLINICAL TRIAL BRIEFING
Ribociclib was evaluated in a randomized, double-blind, placebo-controlled, multi-center study composed of 668 postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had not received prior therapy for advanced disease. Patients on study received ribociclib + letrozole or placebo + letrozole until disease progression or unacceptable toxicity occurred. Ribociclib 600 mg was given once daily for 21 consecutive days followed by seven days off and 2.5 mg of letrozole was given once daily continuously. The primary endpoint of the study was progression-free survival (PFS) as measured by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Additionally, overall response rate (ORR) was evaluated. 27.8% of the ribociclib + letrozole group experienced PFS events compared to 44.9% for placebo + letrozole. Median PFS was not reached in the ribociclib + letrozole group (95% CI: 19.3, not reached) compared to 14.7 months for placebo + letrozole (95% CI:
13.0, 16.5) corresponding to a hazard ratio of 0.556 (95% CI: 0.429 to 0.720). ORR as determined by patients with measureable disease was 52.7 for ribociclib + placebo (95% CI: 46.6, 58.9) compared to 37.1 placebo + letrozole (95% CI: 31.1, 43.2). PROJECTED U.S. SALES (USDm)
DOSING
Administer orally at a recommended starting dose of 600 mg once daily for 21 consecutive days followed by seven days off treatment in repeating cycles. May be taken with or without food. Dose adjustments may be made depending on individual patient response. SAFETY
Common Adverse Events: (≥20%) neutropenia, nausea, fatigue, diarrhea, leukopenia, alopecia, vomiting, constipation, headache, and back pain Warnings and Precautions: QT interval prolongation, hepatobiliary toxicity, neutropenia, and embryo-fetal toxicity
800 600 400 200 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
OTHER AGENTS IN THERAPEUTIC AREA
• Ibrance® (palbociclib)
Specialty Pipeline Report – Q2 2017
13
Xermelo™ (telotristat ethyl)4,12
Recent Approvals APPROVAL DATE: Feb. 28, 2017 CLASS: Tryptophan hydroxylase inhibitor HOW SUPPLIED: 250 mg tablets MANUFACTURER: Lexicon
INDICATION
SAFETY
Treatment of carcinoid syndrome diarrhea in combination with somatostatin analog (SSA) therapy in adults inadequately controlled by SSA therapy.
Common Adverse Events: (≥5%) nausea, headache, increased gamma-glutamyl transpeptidase (GGT) depression, flatulence, decreased appetite, peripheral edema, and pyrexia Warnings and Precautions: Constipation
CLINICAL TRIAL BRIEFING
Telotristat ethyl was evaluated in a 12-week double-blind, placebocontrolled, randomized, multi-center trial composed of 90 adult patients with welldifferentiated metastatic neuroendocrine tumors and carcinoid syndrome diarrhea who experienced 4–12 daily bowel movements while on SSA treatment. During the study patients received 250 mg of telotristat ethyl or placebo three times daily and maintained prior SSA treatment. Additionally, patients were allowed to take rescue medication for symptom relief as necessary. The primary endpoint of the study was change from baseline in the number of daily bowel movements averaged during the course of treatment. The telotristat ethyl group demonstrated a change of -1.4 bowel movements compared to -0.6 for placebo, corresponding to a treatment difference of -0.8 (p<0.001). DOSING
Administer 250 mg three times daily with food. When administering short-acting octreotide in combination with telotristat ethyl, take octreotide at least 30 minutes after telotristat ethyl. 14
Rare Diseases
STORAGE: 25°C (77°F) with excursions
permitted from 15 to 30°C (59–86°F) PATIENT POPULATION: 1,200 diagnoses in the U.S. yearly
PROJECTED U.S. SALES (USDm)
OTHER AGENTS IN THERAPEUTIC AREA
• Sandostatin® (octreotide) • Somatuline® Depot (lanreotide)
300 200 100 0
2017
2018
USDm – US Dollars, millions Cortellis; Accessed April 7, 2017
2019
2020
2021
Specialty Pipeline Report â&#x20AC;&#x201C; Q2 2017
15
Top Agents to Anticipate
16
Top Agents to Anticipate
Brigatinib4,13
MANUFACTURER: Ariad CLASS: ALK Inhibitor ROUTE: Oral ALIAS: AP-26113
CLINICAL TRIAL BRIEFING
UPCOMING EVENT
Brigatinib was evaluated in an openlabel, multi-center, international, Phase 2 study composed of 222 patients with ALK+ NSCLC who were resistant to Xalkori® (crizotinib). During the study, patients received brigatinib 90 mg or 90 mg for seven days then180 mg (90/180 mg) daily until disease progression, intolerable toxicity, or other reasons for discontinuation occurred. The primary endpoint of the study was confirmed objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The primary endpoint was achieved by 45% of the 90 mg group (97.5% CI: 34-56) and 55% of the 90/180 mg group (97.5% CI: 44-65). Additionally, confirmed complete response (CR) was achieved in 2% of the 90 mg group compared to 5% in the 90/180 mg group. Confirmed partial response (PR) was achieved by 43% of the 90 mg group and 50% of the 90/180 mg group.
PDUFA – April 29, 2017
Oncology
TARGET INDICATION: Non-small-cell
lung cancer (NSCLC) with ALK genetic mutation PATIENT POPULATION: 4–5% of NSCLC patients have ALK genetic mutation
CURRENT STATUS: FDA filing completed
STATUS
Accelerated Approval, Breakthrough, Orphan, and Priority Review
PROJECTED SALES NOT AVAILABLE
SAFETY
The most common adverse events of any grade related to treatment (≥15% overall frequency) were nausea, diarrhea, and increased blood creatine phosphokinase.
Specialty Pipeline Report – Q2 2017
17
Top Agents to Anticipate
Cerliponase alfa 4,14,15
MANUFACTURER: BioMarin CLASS: Tripeptidyl peptidase stimulator
(enzyme replacement) ROUTE: Intracerebroventricular infusion
CLINICAL TRIAL BRIEFING
UPCOMING EVENT
Cerliponase alfa was evaluated in an open-label Phase 1/2 study composed of 24 patients with CLN2 disease. During the study, patients received 300 mg of cerliponase alfa every other week for at least 48 weeks. The primary endpoint was clinical motor and language function (ML) score as determined by a CLN2 disease-specific rating scale compared to historical control data in an untreated population. Patients receiving cerliponase alfa demonstrated reduction of decline in ML score of 0.32 points/48 weeks (p<0.0001) compared to the untreated population which had a rate of decline of 2.0 points/48 weeks. An extension study is ongoing.
PDUFA – April 27,2017
Rare Diseases
ALIAS: BMN-190, tripeptidyl-peptidase 1
enzyme replacement therapy (LINCL), Brineura™ TARGET INDICATION: CLN2 disease (Batten disease)
PATIENT POPULATION: 1 in 200,000 CURRENT STATUS: FDA filing completed
STATUS
Breakthrough, Orphan PROJECTED U.S. SALES (USDm) 60 40 20 0
2017
2018
2019
SAFETY
The most common adverse events included pyrexia, hypersensitivity, seizure, epilepsy, vomiting, and headache.
18
USDm – US Dollars, millions Cortellis; Accessed March 22, 2017
2020
2021
Top Agents to Anticipate
Edaravone4,16,17
MANUFACTURER: Mitsubishi Tanabe CLASS: Antioxidant ROUTE: Intravenous
CLINICAL TRIAL BRIEFING
UPCOMING EVENT
Edaravone was evaluated in a doubleblind, parallel-group, Phase 3 study composed of 137 patients with ALS. Following a 12-week observation period, patients received 60 mg of edaravone or placebo for six cycles of treatment. Each cycle consisted of 10 days of treatment over two weeks followed by 14 days off for 24 weeks. The primary endpoint of the study was change in ALS Functional Rating Scale-Revised (ALSFRS-R) score at Week 24. Mean change in ALSFRS-R score was -5.01 ± 0.64 for edaravone and -7.50 ± 0.66 for placebo, corresponding to a treatment difference of 2.49 ± 0.76 (p=0.001). Additionally, ALS Assessment Questionnaire (ALSAQ40) scores were evaluated and demonstrated a difference between groups of -8.79 ± 4.03 (p=0.031) in favor of edaravone.
PDUFA – June 16, 2017
Rare Diseases
ALIAS: Norphenazone, MCI-186,
norantipyrine, Radicut®, Radicava™ TARGET INDICATION: Amyotrophic lateral sclerosis (ALS)
PATIENT POPULATION: 30,000 in the U.S. CURRENT STATUS: FDA filing completed
STATUS
Orphan PROJECTED GLOBAL SALES (USDm) 55 50 45 40
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed March 23, 2017
In an extension study for an additional 24 weeks, patients from the original study received edaravone 60 mg once daily for six cycles with no placebo group. The difference between groups (edaravone in both studies vs placebo in the original study then edaravone in the extension) was 4.17 ± 1.40 (p=0.004) for ALSFRS-R and -10.71 ± 4.51 (p=0.02) for ALSAQ40. SAFETY
The most common adverse events were contusion and dysphagia.
Specialty Pipeline Report – Q2 2017
19
Top Agents to Anticipate
Midostaurin4,18,19,20
MANUFACTURER: Novartis CLASS: TKI ROUTE: Oral ALIAS: Benzoyl-staurosporine, CGP-41251,
CLINICAL TRIAL BRIEFING
UPCOMING EVENT
Midostaurin was evaluated in a randomized, double-blind, placebocontrolled international Phase 3 study composed of 717 newly diagnosed AML patients with FLT-3 genetic mutation. During the study, in addition to standard induction with daunorubicin plus cytarabine and consolidation chemotherapy of high dose cytarabine, patients received 50 mg of midostaurin or placebo on days 8–21 of each cycle for up to 12 cycles or until relapse or the occurrence of intolerable adverse events. Patients achieving a complete remission after consolidation chemotherapy continued treatment with midostaurin or placebo for one year. The primary endpoint of the study was median overall survival (OS). Median OS was 74.7 months for the midostaurin group and 25.6 months for placebo (p=0.0074), corresponding to an improvement of 23% in OS for midostaurin.
Estimated PDUFA – May 14, 2017
SAFETY
The most common adverse events were nausea, vomiting, diarrhea, neutropenia, thrombocytopenia, and anemia.
20
Oncology
STI-412, PKC-412, PKC-412A, CGP-62221, CGP-52421, Rydapt® TARGET INDICATION: Acute myeloid leukemia (AML) with FLT-3 genetic mutation
PATIENT POPULATION: One-third of AML
cases are FLT-3 mutation positive (~7127 estimated new cases in 2017) CURRENT STATUS: FDA filing completed
STATUS
Breakthrough, Priority Review PROJECTED GLOBAL SALES (USDm) 400 300 200 100 0
2017
2018
2019
USDm – US Dollars, millions Cortellis; Accessed March 24, 2016
2020
2021
Top Agents to Anticipate
Nonacog Beta Pegol4,21,22
MANUFACTURER: Novo Nordisk CLASS: Long-acting recombinant
glycoPEGylated factor IX ROUTE: IV ALIAS: GlycoPEGylated factor IX
CLINICAL TRIAL BRIEFING
UPCOMING EVENT
Nonacog beta pegol was evaluated in a multi-national, randomized, singleblind trial composed of 74 previously treated patients with hemophilia B. During the study, patients received 10 or 40 IU/kg of nonacog beta pegol once weekly as prophylaxis for 52 weeks or on-demand treatment of 40 IU/kg for 28 weeks. A primary efficacy endpoint was hemostatic effect when treating a bleeding episode. Successful hemostatic responses occurred in 92.4% of all treated patients. By group, successful hemostatic responses were demonstrated in 86.9% of the 10 IU/kg group, 97.1% of the 40 IU/kg group, and 95.1% of the on demand group. Additionally, the number of injections required to treat a bleeding episode was evaluated. Overall, 87% were treated with one injection, 10.4% with two injections, 0.9% with three injections, and 1.7% with four or more injections.
Estimated PDUFA – May 16, 2017
Rare Disease
(hemophilia B), recombinant coagulation factor IX (long-acting PEGylated, hemophilia B), GlycoPEG-FIX, NN-7999, N9-GP, rFIX glycoPEGylated, NNC-01560000-0009, Refixia®
TARGET INDICATION: Hemophilia B PATIENT POPULATION: 3,400 patients in the U.S. CURRENT STATUS: FDA filing completed
STATUS
Orphan PROJECTED GLOBAL SALES (USDm) 150 100 50 0
2017
2018
2019
2020
2021
USDm – US Dollars, millions Cortellis; Accessed April 4, 2017
SAFETY
No deaths, thromboembolic events, allergic reactions, or development of inhibitors occurred in patients during the course of the study. The most commonly reported adverse events were nasopharyngitis (13.5%), influenza (10.8%), and upper respiratory tract infections (10.8%).
Specialty Pipeline Report – Q2 2017
21
Valbenazine4,23
Top Agents to Anticipate
Rare Disease
MANUFACTURER: Neurocrine, Mitsubishi
ALIAS: NBI-98854, NBI-98782, NBI-136110,
Tanabe CLASS: VMAT2 inhibitor ROUTE: Oral
MT-5199, valbenazine tosylate, Ingrezza™ TARGET INDICATIONS: Tardive dyskinesia (TD)
PATIENT POPULATION: 20–50% of long term
users of dopamine blockers and antipsychotics may develop TD CURRENT STATUS: FDA filing completed
CLINICAL TRIAL BRIEFING
Valbenazine was evaluated in a Phase 3 double-blind, parallel group, placebo-controlled trial composed of 234 patients with moderate-to-severe neuroleptic-induced TD with underlying schizophrenia, schizoaffective disorder, or mood disorder. During the study, patients received valbenazine 40 or 80 mg or placebo for six weeks. Concomitant use of antipsychotic medications was allowed. The primary endpoint was change from baseline on the Abnormal Involuntary Movement Scale (AIMS) score as assessed by blinded central raters. The 80 mg valbenazine group demonstrated a mean change in baseline AIMS score of -3.2 compared to -0.1 for placebo (p<0.0001). The 40 mg valbenazine group demonstrated a mean change in baseline AIMS score of -1.9 vs. -0.1 for placebo (p=0.0021). SAFETY
The most common adverse event was somnolence. UPCOMING EVENT
PDUFA – April 11, 2017 STATUS
Breakthrough, Fast Track, and Priority Review
22
PROJECTED U.S. SALES (USDm) 800 600 400 200 0
2017
2018
2019
USDm – US Dollars, millions Cortellis; Accessed April 4, 2017
2020
2021
Specialty Pipeline Report â&#x20AC;&#x201C; Q2 2017
23
24
Recent Specialty Drug Approvals24,25 DRUG NAME
APPROVED
DRUG CLASS MECHANISM
ROUTE
APPROVAL DATE
Austedo™ (deutetrabenazine) Teva
Treatment of chorea associated with Huntington’s disease
VMAT2 inhibitor
Oral
April 3, 2017
Ocrevus™ (ocrelizumab) Genentech
Relapsing and primary progressive forms of multiple sclerosis
CD20-directed cytolytic antibody
IV
March 28, 2017
Dupixent® (dupilumab) Regeneron and Sanofi-Aventis
Moderate-to-severe atopic dermatitis
IL-4 receptor alpha antagonist
Sub-Q
March 28, 2017
Zejula™ (niraparib) Tesaro
Ovarian, fallopian tube, and peritoneal cancer
PARP inhibitor
Oral
March 27, 2017
Kisqali® (ribociclib) Novartis
HR+/HER2- breast cancer
CDK 4/6 inhibitor
Oral
March 13, 2017
Xermelo™ (telotristat ethyl) Lexicon
Carcinoid syndrome diarrhea
Tryptophan hydroxylase inhibitor
Oral
Feb. 28, 2017
Revlimid® (lenalidomide)* Celgene
Maintenance treatment of multiple myeloma following autologous hematopoietic stem cell transplant
Thalidomide analog
Oral
Siliq™ (brodalumab) Valeant
Moderate-to-severe plaque psoriasis
IL-17RA antagonist
Sub-Q
Feb. 15, 2017
Emflaza™ (deflazacort) PTC
Duchenne muscular dystrophy
Corticosteroid
Oral
Feb. 9, 2017
Imbruvica® (ibrutinib)* AbbVie, Janssen
Marginal zone Lymphoma
Bruton’s tyrosine kinase (BTK) inhibitor
Oral
Jan. 18, 2017
Feb. 22, 2017
*Expanded indication or new formulation
Specialty Pipeline Report – Q2 2017
25
Late-Stage Pipeline Agents4,26 DRUG NAME MANUFACTURER
PROPOSED INDICATION(S)
DRUG CLASS MECHANISM
ROUTE
UPCOMING EVENTS
Acalabrutinib AstraZeneca, Acerta
Chronic lymphocytic lymphoma (CLL)
BTK inhibitor
Oral
FDA decision in early 2018
Brigatinib Ariad
Non-small-cell lung cancer, ALK+
ALK and ROS1 inhibitor, EGFR antagonist
Oral
PDUFA – April 29, 2017
Enasidenib Agios, Celgene
Acute myeloid leukemia (AML), IDH2+
IDH-2 inhibitor
Oral
PDUFA – Aug. 30, 2017
Epoetin alfa biosimilar Hospira, Pfizer
Same indications as Epogen® and Procrit®
Erythropoiesis stimulating agent
Sub-Q
FDA decision in mid-2017
Fostamatinib Rigel
Immune thrombocytopenic purpura
TKI
Oral
FDA decision in early 2018
Gilteritinib Astellas
AML, FLT3+
TKI
Oral
FDA decision in early 2018
Midostaurin Novartis
AML, FLT3+
TKI
Oral
Estimated PDUFA – May 14, 2017
Neratinib Puma
Breast cancer, HER2+
TKI
Oral
Estimated PDUFA – July 20, 2017
Pegfilgrastim biosimilar Mylan
Same indications as Neulasta®
Leukocyte growth factor
Sub-Q
PDUFA – Oct. 9, 2017
Pegfilgrastim biosimilar CHS-1701 Coherus
Same indications as Neulasta®
Leukocyte growth factor
Sub-Q
PDUFA – June 9, 2017
Ataluren PTC
Duchenne muscular dystrophy
Nonsense transcript modulator
Oral
PDUFA – Oct. 24, 2017
Cerliponase alfa BioMarin
CLN2 Batten disease
Enzyme replacement
IV
PDUFA – April 27, 2017
Edaravone Mitsubishi Tanabe
Amyotrophic lateral sclerosis (ALS)
Antioxidant
IV
PDUFA – June 16, 2017
Emicizumab Genentech
Hemophilia A
Bispecific monoclonal antibody
Sub-Q
FDA decision in late 2017
Eptacog alfa (LR769) LFB
Hemophilia A and B
Factor VIIa
IV
FDA decision in late 2017
Nonacog beta pegol (N9-GP/NN7999) Novo Nardisk
Hemophilia B
Factor IX
IV
Estimated PDUFA – May 16, 2017
Pegvaliase BioMarin
Phenylketonuria (PKU)
Enzyme substitute
Sub-Q
FDA decision in early/mid 2018
Plasminogen Prometic
Hypoplasminogenemia
Plasminogen replacement
IV
FDA decision in mid/late 2017
Oncology
Rare Diseases
26
Late-Stage Pipeline Agents4,26 DRUG NAME MANUFACTURER
PROPOSED INDICATION(S)
DRUG CLASS MECHANISM
ROUTE
UPCOMING EVENTS
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
Dimethyl fumarate Almirall
Psoriasis
Unknown
Oral
FDA decision in mid-to-late 2017
Guselkumab Janssen, Morphosys
Psoriasis
IL-23 inhibitor
Sub-Q
Estimated PDUFA – Nov. 17, 2017
Infliximab biosimilar SB-2 Samsung Bioepis, Merck
Same indications as Remicade®
TNF blocker
IV
FDA decision in early 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
Estimated PDUFA – Sept. 23, 2017
Abaloparatide Radius
Osteoporosis
Parathyroid hormone-related protein analog
Sub-Q
PDUFA – June 30, 2017
Benralizumab AstraZeneca
Severe asthma
IL-5 antagonist
Sub-Q
PDUFA – March 29, 2017
Glecaprevir + pibrentasvir AbbVie
Hepatitis C, pangenotypic
NS3/4A protease inhibitor + NS5A inhibitor
Oral
Estimated PDUFA – Aug. 8, 2017
Ibalizumab TaiMed, Theratechnologies
HIV
HIV-1 entry inhibitor
IV
FDA decision in late 2017
Romosozumab Amgen, UCB
Osteoporosis
Sclerostin inhibitor
Sub-Q
PDUFA – July 19, 2017
Voxilaprevir + sofosbuvir + velpatasvir Gilead
Hepatitis C, pangenotypic
NS3 protease inhibitor + NS5B polymerase inhibitor + NS5A inhibitor
Oral
PDUFA – Aug. 8, 2017
Immunology and Multiple Sclerosis
Other
PDUFA listed when available; estimated PDUFA is based on FDA filing date; "FDA decision" is used when no exact PDUFA date can be located
Specialty Pipeline Report – Q2 2017
27
New Indications, Combinations, and Formulations4,26 DRUG NAME MANUFACTURER
CURRENT INDICATION
PROPOSED EXPANDED INDICATION(S)
CURRENT DOSING
UPCOMING EVENTS
Actemra® (tocilizumab) Genentech
Rheumatoid arthritis
Giant cell arteritis
Sub-Q
FDA decision in mid-2017
Austedo™ (deutetrabenazine) Teva
Chorea associated with Huntington’s disease
Tardive dyskinesia
Oral
PDUFA – Aug. 30, 2017
Benlysta® (belimumab) GlaxoSmithKline
Lupus
Lupus – new dose route
Sub-Q
Estimated PDUFA – July 23, 2017
Cabometyx™ (cabozantinib) Exelixis
Renal cell carcinoma
Hepatocellular carcinoma
Oral
FDA decision in early 2018
Haegarda® (C1 esterase inhibitor, human) CSL Behring
Hereditary angioedema
Hereditary angioedema – new dose route
Sub-Q
FDA decision in mid-2017
Imbruvica® (ibrutinib) AbbVie, Janssen
Mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma with or without 17p deletion, Waldenstrom’s macroglobulinemia, and marginal zone lymphoma
Graft versus host disease
Oral
Estimated PDUFA – Oct. 4, 2017
Lynparza™ (olaparib) AstraZeneca
Ovarian cancer, BRCA+ after three or more previous chemotherapies
Relapsed platinum sensitive ovarian cancer in a maintenance setting
Oral
Estimated PDUFA – Sept. 28, 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
Pomalyst® (pomalidomide) + Darzalex® (daratumumab) Celgene, Janssen
Multiple myeloma as separate treatments
Multiple myeloma – new combination
Oral, IV
FDA decision in late 2017
Praluent® (alirocumab) Sanofi, Regeneron
Hypercholesterolemia
Hypercholesterolemia – once monthly dose formulation
Sub-Q
PDUFA – April 24, 2017
Rituxan® (rituximab) Genentech, Halozyme
Non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis, and microscopic polyangiitis
Non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, granulomatosis, and microscopic polyangiitis – new dose route
Sub-Q
PDUFA – June 26, 2017
Simponi ARIA® (golimumab) Janssen
Rheumatoid arthritis
Psoriatic arthritis and ankylosing spondylitis
IV
Estimated PDUFA – Oct. 21, 2017
Soliris® (eculizumab) Alexion
Paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome
Myasthenia gravis
IV
Oct. 23, 2017
Stelara® (ustekinumab) Janssen
Psoriasis, psoriatic arthritis, and Crohn’s disease in adult patients
Psoriasis in pediatric patients
Sub-Q, IV
Estimated PDUFA – Oct. 15, 2017
28
DRUG NAME MANUFACTURER
CURRENT INDICATION
PROPOSED EXPANDED INDICATION(S)
CURRENT DOSING
UPCOMING EVENTS
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
Zykadia® (ceritinib) Novartis
Non-small-cell lung cancer, ALK+, after previous treatment with Xalkori® (crizotinib)
Non-small-cell lung cancer, ALK+, first-line setting
Oral
FDA decision in mid-to-late 2017
PDUFA listed when available; estimated PDUFA is based on FDA filing date; "FDA decision" is used when no exact PDUFA date can be located
Specialty Pipeline Report – Q2 2017
29
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 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 health care 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.
30
References 1.
Fast track, accelerated approval and priority review. Food and Drug Administration Website. fda.gov/%20forconsumers/byaudience%20/%20 forpatientadvocates/%20 speedingaccesstoimportantnewtherapies/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.
3.
Frequently Asked Questions: Breakthrough Therapies. FDA Website. fda.gov/RegulatoryInformation/%20Legislation/ FederalFoodDrugandCosmeticActFDCAct/%20SignificantAmendmentstotheFDCAct/FDASIA/ucm341027.htm. Accessed December 2013.
4.
Cortellis™. Clarivate Analytics; cortellis.thomsonreuterslifesciences.com/ngg/login.do. Accessed March, April 2017.
5.
Siliq™ [package insert]. Bridgewater, NJ: Valeant. 2017.
6.
Emflaza™ [package insert]. Northbrook, IL: Marathon. 2017.
7.
Austedo™ [package insert]. North Wales, PA: Teva. 2017
8.
Dupixent® [package insert]. Tarrytown, NY: Regeneron and Bridgewater, NJ: sanofi-aventis. 2017.
9.
Zejula™ [package insert]. Waltham, MA: Tesaro. 2017.
10.
Ocrevus™ [package insert]. South San Francisco, CA: Genentech. 2017.
11.
Kisqali® [package insert]. East Hanover, NJ: Novartis. 2017.
12.
Xermelo™ [package insert]. The Woodlands, TX: Lexicon. 2017.
13.
Camidge DR, Tiseo M, Ahn MJ, et al. Brigatinib in crizotinib-refractory ALK+ NSCLC: Central assessment and updates from ALTA, a pivotal randomized phase 2 trial. Presented at the 17th World Conference on Lung Cancer, Dec. 4-7 2016, Vienna, Austria. phx.corporate-ir.net/External. File?item=UGFyZW50SUQ9MzYwMzEzfENoaWxkSUQ9LTF8VHlwZT0z&t=1&cb=636167184406228837.
14.
Schultz A, Specchio N, Gissen P, et al. Long-term safety and efficacy of intracerebroventricular enzyme replacement therapy with cerliponase alfa in children with CLN2 disease: interim results for an ongoing multicenter, multinational extension study. Abstracts Molecular Genetics and Metabolism 120 (2016) S17–S145. mgmjournal.com/article/S1096-7192(16)30730-2/abstract.
15.
BioMarin announces positive data from cerliponase alfa program for treatment of CLN2 disease, a form of Batten disease, at 12th annual WORLDSymposium™ 2016. Globe Newswire Website. globenewswire.com/news-release/2016/03/03/816408/0/en/BioMarin-Announces-Positive-Data-From-Cerliponase-AlfaProgram-for-Treatment-of-CLN2-Disease-a-Form-of-Batten-Disease-at-12th-Annual-WORLDSymposium-TM-2016.html. Accessed March 22, 2017.
16.
Tanaka M, Sakata T, Palumbo J, and Akimoto M. A 24-week, phase III, double-blind, parallel-group study of edaravone (MCI-186) for treatment of amyotrophic lateral sclerosis (ALS). Neurology April 5, 2016 vol. 86 no. 16 Supplement P3.189.
17.
Palumbo J, Sakata T, Tanaka M, and Akimoto M. Sustained efficacy for up to 12 months in an active extension of a phase III study of edaravone (MCI-186) for treatment of amyotrophic lateral sclerosis (ALS). Neurology April 5, 2016 vol. 86 no. 16 Supplement P3.190
18.
Alliance of Clinical Trials in Oncology. A Phase III Randomized, Double-Blind Study of Induction (Daunorubicin/Cytarabine) and Consolidation (High-Dose Cytarabine) Chemotherapy + Midostaurin (PKC412) (IND #101261) or Placebo in Newly Diagnosed Patients < 60 Years of Age With FLT3 Mutated Acute Myeloid Leukemia (AML). In: ClinicalTrials.gov [Internet]. Bethesda (MD): National Library of Medicine (US). 2000- [cited 2017 Jan 25]. Available from: clinicaltrials.gov/ show/NCT00651261 NLM Identifier: NCT00651261.
19.
Novartis drug PKC412 (midostaurin) improves overall survival by 23% in global phase III study of AML patients with FLT3 mutations. Novartis Website. novartis. com/news/media-releases/novartis-drug-pkc412-midostaurin-improves-overall-survival-23-global-phase-iii. Accessed March 24, 2017.
20.
Gallogly MM, Lazarus HM. Midostaurin: an emerging treatment for acute myeloid leukemia patients. Journal of blood medicine. 2016;7:73.
21.
Novo Nordisk files for regulatory approval in the US of long-acting factor IX for the treatment of haemophilia. Nasdaq Global Newswire Website. globenewswire. com/news-release/2016/05/16/840336/0/en/Novo-Nordisk-files-for-regulatory-approval-in-the-US-of-long-acting-factor-IX-for-the-treatment-of-haemophilia-B. html. Accessed April 3, 2017.
22.
Collins PW, Young G, Knobe K, et al. Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial. Blood. 2014;124(26):3880-3886.
23.
Hauser R, Factor S, Marder S, et al. KINECT 3: A randomized, double-blind, placebo-controlled phase 3 trial of valbenazine (NBI-98854) for tardive dyskinesia (Pl02.003). Neurology April 5, 2016 vol. 86 no. 16 Supplement PL02.003.
24.
New drug approvals. Drugs.com Website. drugs.com/newdrugs.html. Accessed April 3, 2017.
25.
New indications & dosage forms for existing drugs. Drugs.com Website drugs.com/new-indications.html. Accessed April 3, 2017.
26.
PDUFA Calendar. Biopharmacatalyst.com Website. biopharmcatalyst.com/calendars/pdufa-calendar. Accessed April 3, 2017.
Specialty Pipeline Report – Q2 2017
31
877.977.9118 OR VISIT diplomat.is @diplomatrx CALL TOLL-FREE
4100 S. Saginaw St. Flint, MI 48507
LEGAL DISCLAIMER The information herein is for educational purposes only and may not be construed as medical advice. Diplomat Pharmacy Inc. takes no responsibility for the accuracy or validity of the information herein, nor the claims or statements of any manufacturer. Copyright Š 2017 by Diplomat Pharmacy Inc. Diplomat is a registered trademark of Diplomat Pharmacy Inc. All rights reserved. CS-68191-0517