Prescribe Right Pharmaceutical Pipeline Update for October 3

Four FDA approvals during the last week in September:

• The FDA approved Verastem’s duvelisib (Copiktra) on 9/24/18 ahead of the Oct 5, 2018 PDUFA Date, for the treatment of patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) or relapsed/refractory follicular lymphoma. Duvelisib has orphan drug and fast track Priority Designations.
• The FDA approved Pfizer’s dacomitinib (Vizimpro) on 9/27/2018, 3 days ahead of its PDUFA Date, as first-line treatment of patients with metastatic non-small cell lung cancer with epidermal growth factor receptor (EGFR) exon 19 deletion or exon 21 L858R substitution mutations, as detected by an FDA-approved test. WAC was set at $12,400 for one month’s treatment.
• The FDA approved Regeneron Pharmaceuticals’ and Sanofi Aventis’ cemiplimab (Libtayo) on 9/28/18, ahead of its Oct 28, 2018 PDUFA Date, for the treatment of patients with metastatic cutaneous squamous cell carcinoma (CSCC) or locally advanced CSCC who are not candidates for curative surgery or curative radiation. The WAC for a three-week treatment cycle is $9,100. The drug has a Breakthrough Therapy Priority Designation.
• The FDA approved Lilly’s galcanezumab (Emgality) on 9/28/2018, 2 days ahead of its PDUFA Date, as a once-monthly, self-administered, subcutaneous injection for the preventive treatment of migraine in adults. The drug had Fast Track Priority Designation. The WAC for galcanezumab is $575 once-monthly, or $6,900 annually, which matches the price set for erenumab (Aimovig) and fremanezumab (Ajovy). Lilly has a program to cover the co-pay for patients with commercial insurance for at least 12-months. Amgen/Novartis (erenumab, Aimovig) and Teva (fremanezumab, Ajovy) also have programs to cover co-pays for patients with commercial insurance.

THIRTEEN Updates on products with PDUFA Dates and/or Priority Designations

• Pfizer is enrolling patients in the Phase III CROWN trial (NCT03052608) comparing lorlatinib with crizotinib as a first-line therapy for ALK-positive NSCLC. Lorlatinib has a PDUFA Date of November 30, 2018 with Orphan Drug and Breakthrough Priority Designations.
• Jazz filed an NDA for solriamfetol. The drug has a PDUFA Date of Dec 20, 2018, and an Orphan Drug Priority Designation.
• In the Phase III, CAPSTONE-1 trial, nausea was less common with a single dose of Genentech’s and Shionogi’s baloxavir marboxil rather than 5 days of oseltamivir. PDUFA Date of Dec 24, 2018.
• Govitecan is the active metabolite of irinotecan. It is bound to sacituzumab, a trophoblastic antigen-2 antibody, a receptor found on many tumors. Immunomedics is seeking approval for the treatment of metastatic triple-negative breast cancer in patients that have previously received at least two prior therapies for metastatic disease. Immunogenics has an ongoing Phase III trial evaluating sacituzumab govitecan in the treatment of triple negative breast cancer. The drug’s PDUFA Date is Jan 18, 2019.
• J&J announced that in a Phase III trial, esketamine nasal spray added to a new antidepressant did not improve Montgomery-Asberg Depression Rating Scale (MADRS) total score compared to monotherapy with a new antidepressant in patients with treatment-resistant depression. A preliminary report had described the numerical advantage with esketamine, but a more detailed report indicated the data was not statistically significant. No PDUFA Date. Breakthrough Therapy Priority Designation.
• In a Phase II trial of 130 female patients with HR+ breast cancer, using Syndax’s entinostat or placebo in exemestane treated patients, the entinostat group increased overall survival by 9 months, and progression free survival by 2 months. Syndax announced that an interim analysis from 76 NSCLC patients in the Phase Ib/II ENCORE 601 trial, treatment with entinostat and pembrolizumab had an objective response rate (ORR) of 10% and progression free survival of 2.8 months, which did not meet the prespecified ORR endpoint. Entinostat has a Breakthrough Therapy Priority Designation.
• In an ongoing Phase III trial, TG Therapeutics’ ublituximab (Orphan Drug Priority Designation) in combination with its umbralisib (Orphan Drug Priority Designation) is being compared to obinutuzumab plus chlorambucil in CLL. Topline data was originally expected in 2Q18 and later changed to 3Q18. In late September 2018, TG Therapeutics announced that an interim analysis found the data too immature to calculate overall response rate, so the company will now focusing on Progression Free Survival and hopes to announce results in 2019. Additionally, TG Therapeutics announced that in a 48-week, 48 patient, phase II trial, treatment with ublituximab resulted in median B cell depletion of >99% and a decrease in mean T2 lesion volume of 10% in patients with relapsing multiple sclerosis.
• Aldeyra Therapeutics announced that in a 12-week, 300 patient, Phase IIb trial, reproxalap reduced the Four-Symptom Ocular Dryness Score and the Overall Ocular Discomfort Symptom Score compared to placebo in patients with dry eye disease. A phase III trial of reproxalap is currently ongoing in patients with non-infectious anterior-uveitis and a phase 2 dry eye syndrome study. The drug has an Orphan Drug Priority Designation.
• Alnylam announced interim 3-month data from 41 patients in the Phase III, ENVISION trial, where treatment with givosiran lowered Urinary Aminolevulinic Acid compared to placebo in patients with acute intermittent porphyria. The drug has Orphan Drug and Breakthrough Therapy Priority Designations. The drug has EU EMA PRIME and orphan status.
• GeNeuro announced 6-month results in a 64 patient, Phase IIa safety trial, where GNbAC1 given concurrently with the patient’s diabetes regimen was found to be well tolerated in type 1 diabetic patients. Priority Designation: Orphan Drug.
• Reata announced that in a Phase II trial, treatment with bardoxolone (orphan drug Priority Designation) increased eGFR by 5.5 mL/min/1.73 m2 in 28 Type 1 diabetic chronic kidney disease (CKD) patients and by 8.0 mL/min/1.73 m2 in 26 patients with IgA nephropathy.
• Lumateperone may have a lower incidence of movement, metabolic and cardiovascular ADR compared to other anti-psychotics. One analyst felt it was comparable to risperidone. Intra-Cellular Therapies submitted an NDA in September 2018 for lumateperone which has a Fast Track Priority Designation.
• Gilteritinib: orphan status in EU.

FOUR additional updates:

• Incyte announced interim results from a Phase I/II trial, where treatment with epacadostat in combination with pembrolizumab resulted in an objective response rate of 29% regardless of high PD-L1 or IDO1 expression and a progression free survival of 17% at 18 months in patients with relapsed/refractory non-small cell lung cancer that had received platinum-based chemotherapy but had no prior exposure to immune checkpoint inhibitors. The study included patients with EGFR mutations and patients that were intolerant to EGFR inhibitors.
• BioCardia announced preliminary results from the first 10 patients in the Phase III Trial, suggested that a 9-month open label treatment with CardiAMP improved New York Heart Association class and Six Minute Walk Distance in patients with ischemic cardiomyopathy, LVEF 20-40%. BioCardia will present   1-year data from CardiAMP-HF at the November 2018 AHA meeting.
• Novo announced that in the 26-week, 59 patient, Phase II REAL 3 trial, weekly somapacitan was similar to daily somatropin in annualized height velocity in children with growth hormone deficiency.
• In July 2018, the FDA placed a hold on Sarepta Therapeutics’ microdystrophin gene therapy for Duchenne muscular dystrophy trial enrollment due to the presence of a trace fragment of DNA plasmid in one lot of the material. The hold was lifted in September 2018 and enrollment resumed.

​You can access up-to-date information on all drugs in the late stages of development with the Prescribe Right Pharmaceutical Pipeline Tracker.