ear ly 2019 outlook report extract - informa/media/informa-shop-windo… · february 2019 / 1 early...

February 2019 / 1

Early 2019 Outlook Report

EA RLY 2019 OUTLOOK REPORT EXTRACT

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February 2019 / 2


Summary In this report, we cover catalysts from 23 drugs, devices and diagnostics expected to occur in early 2019. For each drug, the likelihood of Phase/PDUFA review success and overall Likelihood of Approval (LOA) given their particular phase, drug class, and disease group are provided. The results of the catalysts highlighted in our Q4 2018 Outlook Report can be found on Page 4. At the end of this report, we have included a list of Large Impact catalysts through early 2019. The catalyst list is also provided in Excel by downloading the supplemental material at the top of this page. Like our report? Have any questions or feedback? Please let us know at [email protected].

About the Author Biomedtracker is an independent research service that offers proprietary clinical assessments of developmental drugs within a comprehensive and intuitive drug information database. Clients from the pharmaceutical, biotech, and investment industries rely on Biomedtracker for its insight on the likelihood of approval, commercial potential, and future data and regulatory catalysts for drugs within the competitive landscape of every important disease and indication. Over recent years, Biomedtracker has become the leader in providing objective information alongside evidence-based clinical assessments and investment research on pipeline drugs worldwide. For more information on getting direct access to Biomedtracker, please email [email protected]. Meddevicetracker is an all new medtech intelligence platform that provides clients with real-time data and analysis on medical devices and diagnostics. From the people behind Biomedtracker, comes an event-driven research service for the medical device and diagnostic marketplace. For access to Meddevicetracker please contact your sales representative or email [email protected].

Disclaimer Copyright © 2019 Sagient Research This report is published by Sagient Research (the Publisher). This report contains information from reputable sources and although reasonable efforts have been made to publish accurate information, you assume sole responsibility for the selection, suitability and use of this report and acknowledge that the Publisher makes no warranties (either express or implied) as to, nor accepts liability for, the accuracy or fitness for a particular purpose of the information or advice contained herein. The Publisher wishes to make it clear that any views or opinions expressed in this report by individual authors or contributors are their personal views and opinions and do not necessarily reflect the views/opinions of the Publisher.

February 2019 / 3


Contents Outcomes of Biomedtracker's Large Impact Catalysts from the Q4 2018 Outlook Report ........................... 4

Enfortumab Vedotin for Bladder Cancer (Astellas) ....................................................................................... 6 Margetuximab for Breast Cancer (MGNX) ..................................................................................................... 7

Recorlev for Cushing’s Syndrome (SBBP) ...................................................................................................... 8

Gimoti for Diabetic Gastroparesis (EVOK) ..................................................................................................... 9 Roclatan for Glaucoma / Ocular Hypertension (Ophthalmology) (AERI) ..................................................... 10

Teprotumumab for Graves' Ophthalmopathy/Orbitopathy (HZNP) ............................................................ 10 Esketamine for Major Depressive Disorder (MDD) (JNJ) ............................................................................. 11

Qtrypta for Migraine and Other Headaches (ZSAN) .................................................................................... 12 Selinexor for Multiple Myeloma (MM) (KPTI) .............................................................................................. 13

Mayzent for Multiple Sclerosis (MS) (NVS) .................................................................................................. 14

Solriamfetol for Narcolepsy (JAZZ) .............................................................................................................. 15 Ocaliva for Non-Alcoholic Steatohepatitis (NASH) (ICPT) ............................................................................ 16

HTX-011 for Postsurgical Pain (HRTX) .......................................................................................................... 17 N1539 for Postsurgical Pain (REPH) ............................................................................................................. 18

ResVax for Respiratory Syncytial Virus (RSV) (NVAX) ................................................................................... 19 Filgotinib for Rheumatoid Arthritis (RA) (GILD) ........................................................................................... 20

Iclaprim (IV) for Skin and Skin-Structure Infections (Antibacterial) (MTFB) ................................................. 21

Cablivi for Thrombotic Thrombocytopenic Purpura (TTP) (SNY) ................................................................. 22 t:connect Mobile Application for Diabetes Mellitus, Type II (TNDM) .......................................................... 23

ReStore for Motor Recovery (RWLK) ........................................................................................................... 24 ResAppDx for Respiratory Disease (ResApp) ............................................................................................... 24

Acquisition of Loxo Oncology by Eli Lilly ...................................................................................................... 26 CDX-6114 for Phenylketonuria (PKU) (CDXS) .............................................................................................. 26

Early 2019 Large Impact Drug Catalysts……………..…..………………..………………………………………………………………28

Early 2019 Large Impact Device/Diagnostics Catalysts…………………………………………………………………………..…36

February 2019 / 4


Outcomes of Biomedtracker's Large Impact Catalysts from the Q4 2018 Outlook Report Occurred

Date Lead Company Product Market Catalyst Did LOA Predict

Outcome

LOA Before Outcome

LOA After Outcome

10/5/2018 Akcea Tegsedi Metabolic PDUFA for NDA - First Review No 88%

(1% Below Avg.) 100%

(Same As Avg.)

10/12/2018 AcelRx Dsuvia Neurology FDA Advisory Panel Meeting Yes 91%

(8% Above Avg.) 92%

(9% Above Avg.)

10/16/2018 Pfizer Talzenna Oncology PDUFA for NDA - First Review Yes 85%

(3% Above Avg.) 100%

(Same As Avg.)

10/16/2018 Pharnext PXT3003 Neurology Phase III PLEO-CMT - Top-Line

Results N/A

52% (Same As Avg.)

60% (8% Above Avg.)

10/18/2018 GlaxoSmithKline Tivicay/Epivir Infectious disease NDA Filing Yes 69%

(8% Above Avg.) 96%

(8% Above Avg.)

10/18/2018 Takeda Motegrity Gastroenterology

(non inflammatory bowel disease)

FDA Advisory Panel Meeting Yes 92%

(3% Above Avg.) 96%

(7% Above Avg.)

10/23/2018 BeyondSpring Plinabulin Hematology Phase II/III Protective-2 - Top-Line

Results N/A

60% (Same As Avg.)

60% (Same As Avg.)

10/30/2018 Johnson & Johnson Invokana Cardiovascular PDUFA for sNDA - First Review N/A 85%

(Same As Avg.) 100%

(Same As Avg.)

11/2/2018 Trevena Oliceridine Neurology PDUFA for NDA - First Review Yes 78%

(5% Below Avg.) 52%

(Same As Avg.)

11/5/2018 AVEO Tivopath

(Oncology) Oncology Phase III TIVO-3 - Top-Line Results No 35%

(Same As Avg.) 30%

(5% Below Avg.)

11/5/2018 Eli Lilly Trulicity Endocrine Phase III REWIND - Top-Line Results N/A 100%

(Same As Avg.) 100%

(Same As Avg.)

11/10/2018 AstraZeneca Farxiga Endocrine Phase III DECLARE-TIMI58 - Updated

Results at AHA N/A 100%

(Same As Avg.) 100%

(Same As Avg.)

11/23/2018 Novo Nordisk Oral

Semaglutide Endocrine

Phase III PIONEER 6 - Top-Line Results

Yes 76%


(16% Above Avg.)

11/26/2018 Loxo Vitrakvi Oncology PDUFA for NDA - First Review Yes 96%

(14% Above Avg.) 100%

(Same As Avg.)

February 2019 / 5


11/28/2018 Catalyst Firdapse Autoimmune/ immunology

PDUFA for NDA - Second Review Yes 98%

(11% Above Avg.) 100%

(Same As Avg.)

11/29/2018 Alkermes ALKS 3831 Psychiatry Phase III ENLIGHTEN-2 - Top-Line

Results Yes 55%

(4% Above Avg.) 57%

(6% Above Avg.)

12/3/2018 bluebird LentiGlobin Hematology Phase III Northstar-3 - Top Line

Results at ASH No

70% (10% Above Avg.)

65% (5% Above Avg.)

12/3/2018 bluebird LentiGlobin Hematology Phase III Northstar-2 - Updated

Results at ASH No 70%


(5% Above Avg.)

12/10/2018 Marinus Ganaxolone Psychiatry Phase II Magnolia - Top-Line Results N/A 12%

(Same As Avg.) 14%

(2% Above Avg.)

12/23/2018 Apple Tree Partners Brixadi Psychiatry PDUFA for NDA - Second Review Yes 92%


(Same As Avg.)

1/2/2019 Aevi Genomic AEVI-001 Psychiatry Phase II ASCEND (Parts A and B) -

Top-Line Results Yes

50% (1% Below Avg.)

0% (Same As Avg.)

1/7/2019 SAGE SAGE-217 Psychiatry Phase IIa Postpartum Depression -

Top-Line Results Yes 59%

(8% Above Avg.) 61%

(10% Above Avg.)

February 2019 / 6


Drugs Enfortumab Vedotin for Bladder Cancer (Astellas)

Drug Company Partner(s) Indication(s) Date Range Expected Catalyst(s)

Enfortumab Vedotin Astellas Pharma

Seattle Genetics Bladder Cancer 01/01/2019 -

03/31/2019 Phase II EV-201 - Top-Line Results

Phase Disease Group Drug Class Group/Class Phase Success

Group/Class LOA (PTS)

BMT LOA Opinion

III Oncology NME 43.70% 37.19% Above Astellas and Seattle Genetics are developing enfortumab vedotin, an anti-drug conjugate (ADC) targeting nectin-4, a cell adhesion molecule expressed in many solid tumors, for the treatment of urothelial cancer. In March 2018, the U.S. Food and Drug Administration (FDA) granted Breakthrough Designation to enfortumab vedotin based on results from the Phase I trial studying enfortumab vedotin as a monotherapy treatment for patients with metastatic urothelial cancer who were previously treated with immune checkpoint inhibitors (CPIs). Enfortumab vedotin is being studied in two registrational trials, the single-arm Phase II EV-201 trial, and the Phase III EV-301 trial, the latter having a randomized design comparing enfortumab vedotin to the standard of care. Data from EV-201 will be submitted for approval through the FDA’s Accelerated Approval pathway, while the companies plan for data from the global EV-301 trial to support expansion of approval to further markets. Astellas and Seattle Genetics anticipate top-line results from the ongoing Phase II EV-201 study for the first cohort in the first quarter of 2019. EV-201 is a pivotal Phase II trial studying enfortumab vedotin for patients with locally advanced or metastatic urothelial cancer who were previously treated with an immune CPI, and includes patients treated with platinum chemotherapy in the first cohort and patients who have never received platinum-containing treatment as well as cisplatin-ineligible patients in the second cohort. The primary endpoint is objective response rate (ORR), per independent review. Astellas and Seattle Genetics completed patient enrollment for EV-201 for all cohorts in July 2018. In June 2018, from previously released results for a Phase I trial, the ORR for patients taking enfortumab vedotin was 41%, with the ORR at 40% in patients previously treated with a checkpoint inhibitor, 44% in patients without prior checkpoint inhibitor therapy and 39% in patients with liver metastates. Additionally, the interim median overall survival (OS) was 13.6 months. Given these positive early phase results, top-line results from EV-201 are highly anticipated, especially given the high unmet need in the post-platinum/post-CPI patient subset.

February 2019 / 7


Margetuximab for Breast Cancer (MGNX)


Margetuximab MacroGenics, Inc. Green Cross, ZAI Breast Cancer 01/01/2019 -

03/31/2019 Phase III SOPHIA - Top-Line Results



BMT LOA Opinion

III Oncology Biologic 45.83% 43.62% Above MacroGenics is developing margetuximab (MGAH22), an Fc-modified monoclonal antibody, that targets the HER2 oncoprotein, which is overexpressed on the surface of various cancer cells and plays an important role in tumorigenesis, tumor aggressiveness, and outcome in breast and other cancers. In January 2018, MacroGenics announced that the US FDA granted Fast Track designation for the investigation of margetuximab for treatment of patients with metastatic or locally advanced HER2+ breast cancer who have previously been treated with anti-HER2-targeted therapy. Margetuximab is currently in Phase III development for the treatment of breast cancer, and Phase I/II development for the treatment of esophageal and gastric cancer. Top-line results from the pivotal Phase III SOPHIA study of margetuximab for the treatment of patients with HER2+ metastatic breast cancer who have received two prior anti-HER2 therapies and require systemic treatment are anticipated in the first quarter of 2019. SOPHIA is a randomized, open-label, two-arm, interventional Phase III study evaluating margetuximab plus chemotherapy against trastuzumab plus chemotherapy in third-line metastatic breast cancer patients with HER2 expression at the 3+ level by IHC or 2+ level by IHC with gene amplification. The purpose of the study is to determine whether patients treated with margetuximab plus chemotherapy have longer progression-free and overall survival than patients treated with trastuzumab plus chemotherapy. Of note, in January 2018 an independent data safety monitoring committee (DSMC) recommended that the SOPHIA study continue as planned without modification based on a pre-planned interim futility analysis of progression-free survival (PFS). The futility analysis did not allow for early stopping due to efficacy. Data from a previous Phase I basket trial in a limited number of breast cancer patients demonstrated a median PFS of 24.1 weeks, increasing to 34.1 weeks in the Regimen B breast cancer patients (cohorts of 10, 15, and 18 mg/kg administered once every 3 weeks). This early evidence of disease control in Regimen B patients likely translated to the evaluated dose in the SOPHIA study: margetuximab plus chemotherapy (15 mg/kg intravenous) infusion over 120 minutes on day 1 of each 21-day cycle. Top-line PFS results are expected from the SOPHIA study in the first quarter of 2019. The efficacy and safety profile from the SOPHIA study will weigh heavily on the upcoming Biologics License Applications (BLA) that MacroGenics plans to file in 2019.

February 2019 / 8


Recorlev for Cushing’s Syndrome (SBBP)


Recorlev Strongbridge Biopharma plc N/A Cushing's

Syndrome 01/01/2019 - 03/31/2019

Phase III LOGICS - Top-Line Results



BMT LOA Opinion

III Endocrine NME 56.63% 44.83% Above Recorlev is a 2S,4R pure enantiomer of ketoconazole for the treatment of endogenous Cushing’s syndrome being developed by Strongbridge Biopharma. In March 2012, the U.S. Food and Drug Administration (FDA) granted orphan drug designation to Recorlev. Strongbridge anticipates on releasing top-line results from the pivotal Phase III LOGICS trial in the first quarter of 2019. LOGICS is a double-blind, placebo-controlled, randomized withdrawal study assessing Recorlev’s safety and efficacy for patients with endogenous Cushing’s syndrome through three treatment phases. The first being a Recorlev naïve-only dose titration for 14 to 19 weeks, then a randomized-withdrawal phase where subjects blindly receive either Recorlev or placebo for 8 to 9.5 weeks, and thirdly a restoration phase for 8 to 9.5 weeks where patients receive a therapeutic dose of blinded Recorlev or placebo. The primary endpoint of efficacy is comparing the effects of withdrawing to placebo versus continuing treatment with Recorlev on the urinary free cortisol (UFC) level measurement. Approximately half of the randomized subjects have completed the SONICS trial. The LOGICS trial is a supplement to the ongoing Phase III SONICS trial. In August 2018, Strongbridge reported Recorlev to be effective and well tolerated in patients in the SONICS trial. The SONICS trial was a single-arm, open-label study evaluating the safety and efficacy of Recorlev for the treatment of endogenous Cushing’s syndrome with three treatment phases. The study met its primary endpoint with 30% of patients achieving normalization of mean UFC after six months of maintenance treatment without a dose increase. With these results and the anticipated data from the LOGICS trial, Strongbridge plans to meet with the FDA to discuss an accelerated approval in the future. However, safety issues still stand. Ketoconazole has a black-box warning for potentially fatal liver toxicity in the US and was recommended to be withdrawn by the EMA, though since it is recommended in Cushing’s syndrome, where there is a high unmet need, this may not preclude approval of Recorlev. Depending on further data, though, Recorlev may likewise be given a black box warning, which could impact payers. It is also to be noted as a potential competition that Novartis is also in Phase III development of osilodrostat for Cushing’s syndrome with pivotal data to be released later this year as well.

February 2019 / 9


Gimoti for Diabetic Gastroparesis (EVOK)


Gimoti Evoke Pharma, Inc. Mallinckrodt Diabetic Gastroparesis 04/01/2019 PDUFA for NDA

- First Review



BMT LOA Opinion

NDA Gastroenterology (non inflammatory bowel disease) Non-NME 90.91% 33.00% Above

Gimoti (EVK-001) is a formulation of metoclopramide which acts as a dopamine D2 receptor antagonist and a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist. Gimoti is being developed by Evoke Pharma for the treatment of diabetic gastroparesis. In 2014, Mallinckrodt acquired Questcor, thus entering into a partnership with Evoke on the development of Gimoti. Under the current agreement, one single milestone payment from Evoke Pharma to Mallinckrodt will be due one year after FDA approval of Gimoti. In April and May of 2018, Evoke Pharma was granted a patent from the European Patent Office and Mexican Institute of Industrial Property, respectively. In 2017, Gimoti was studied in a Pharmacokinetic Bioequivalence study which the company used to submit a 505(b)(2) NDA application to the FDA. In the 4-way crossover study design, male and female volunteers each received one Reglan Tablet and three different doses of Gimoti in a random sequence. Although the maximum observed plasma concentration (Cmax) analysis for Gimoti showed results slightly lower than the bioequivalence range in a top-line data release, this study produced mixed results as Gimoti showed pharmacokinetics equivalent to Reglan as measured by an area under the curve analysis. Cmax numbers were not disclosed, and it was not clear if Cmax was an FDA criterion for showing bioequivalence in this study at the time of the data release. The company also conducted two Phase III studies of Gimoti, METO-IN-003 (Women) and METO-IN-004 (Men). Data released from the women’s study was obtained by measuring the change from baseline to Week 4 of treatment in the mean gastroparesis (GP) symptom score for the Intent-to-Treat (ITT) population. The change from baseline to Week 4 was not statistically significant, but patients with higher baseline symptom scores demonstrated a significant treatment effect, as well as reduction in nausea and abdominal pain through the study. These results illustrated that Gimoti provided statistically significant symptom relief in women with diabetic gastroparesis, consistent with the FDA’s draft guidance for gastroparesis and that Gimoti 10mg used four times per day for four weeks was well tolerated. Early in 2018, Evoke held a pre-NDA meeting with the FDA to discuss and clarify expectations of items being prepared for inclusion in the NDA for Gimoti. The NDA included a risk management strategy and a post-approval safety study to confirm prior safety findings and rule out possible differences with side effects. The NDA was filed in June 2018 and accepted in August 2018. The target goal date for a first review under the Prescription Drug User Fee Act (PDUFA) is April 1, 2019. Find out more about the full report

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