FDA Updates: Treatment for Duchenne Mutation, Gilead Seeks Remdesivir Approval, Data on ALKS 3831

August 16, 2020

Actions from FDA this week include approval of a second targted treatment for a Duchenne muscular dystrophy mutation, and filings in COVID-19 and blood disorders.

Second treatment for Duchenne mutation. FDA on Wednesday approved the targeted therapy viltolarsen under its accelerated process to treat patients with Duchenne muscular dystrophy in patients who have a gene amenable to exon 53 skipping. About 8% of Duchenne patients have the mutation treatable with viltolarsen, which will be sold as Viltepso by NS Pharma. This is the second treatment approved for these patients.

Duchenne muscular dystrophy is a rare, serious neurological disorder that affects about 1 in 3,500 male births and appears between ages 3 and 6. Genetic mutations cause a loss of dystrophin, which keeps muscle cells intact. Wasting in the pelvic area muscles appears first, followed by weakness and atrophy that spread throughout the body; life-threatening complications include cardiomyopathy and respiratory illness. In a clinical study, viltolarsen caused dystrophin levels to rise from 0.6% of normal to 5.9% of normal at 25 weeks. A post-approval trial will be required.

Remdesivir NDA for COVID-19 filed. On Monday, Gilead Sciences formally filed its New Drug Application (NDA) for remdesivir to treat coronavirus disease 2019 (COVID-19). The drug, which is already available under an FDA emergency use authorization, would take the brand name Veklury, the company said in a statement. Clinical trials show the drug shortens the recovery time from COVID-19 by stopping the virus from copying itself. On Tuesday, authors in the New England Journal of Medicine called for Gilead to do more to improve diversity of enrollees in clinical trials for the drug, since a disproportionate share of patients with COVID-19 are Black and Latino. Meanwhile, The Detroit News reported that FDA rejected a bid by Henry Ford Health System to for approval to use hydroxychloroquine in treating some COVID-19 patients.

ALKS 3831 Schizophrenia Data Published. Alkermes announced Thursday that data from the phase 3 ENLIGHTEN-2 study involving its investigational therapy ALKS 3831 in treatment schizophrenia had been published in the American Journal of Psychiatry. The randomized controlled trial involving 561 patients examined whether the study drug, ALKS 3831 (olanzapine/samidorphan), produced similar antipsychotic effects while causing less weight gain in patients than olanzapine alone. Fewer patients in the group taking ALKS 3831 had weight gain of greater than 10% (17.8% vs 29.8%), and fewer had a weight gain of at least 7% (27.5% vs 42.7%). Increases in waist circumference were smaller among the group taking the study drug. FDA accepted the NDA for ALKS 3831 to treat schizophrenia and bipolar disorder; action is required by November 15, 2020.

Priority Review for umbralisib in previously treated MZL. FDA on Thursday granted priority review designation for TG Therapeutics’ umbralisib for treatment of patients with marginal zone lymphoma (MZL) who have received at least one prior treatment with an anti-CD20 based therapy. In accepting the NDA, FDA set an action date of February 15, 2021 for the MZL indication and separate date of January 15, 2021 for an indication in follicular lymphoma (FL), which will be handled under FDA’s standard review process. According to the company’s statement, no advisory board hearing is planned. Umbralisib is a once-daily, oral, dual inhibitor of PI3K-delta and CK1-epsilon that has been evaluated in the phase 2b UNITY-NHL trial; each group of patients met the primary end point of an overall response rate of 40% to 50%. The drug previously received breakthrough therapy designation in MZL and orphan drug designation for both MZL and FL.

Panel supports pediatric indication for remestemcel-L . FDA’sOncologic Drugs Advisory Committee voted 8-2 Thursday to support approval of remestemcel-L, a cell therapy for the treatment of children with steroid-refractory acute graft-versus-host disease (GVHD). The hearing was set to support the biologics license agreement for the drug for use in this indication. Priority review status has been granted previously. Panelists reviewed trial data from two studies; in the first, a single-arm trial, 55 children who did not respond to steroids for GVHD; the overall response rate was 69.1% after 28 days. In the second, a double-blind, placebo controlled study with 27 patients, the ORR was 64.3% for those who received remestemcel-L with standard of care vs 38.5% for those who received standard of care only. The study drug is made by Mesoblast Limited.