Positive Phase 2 FORWARD-53 Data of WVE-N531, RNS60 Extends Survival in ALS, BLA to be Submitted for Deramiocel

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Welcome to this special edition of Neurology News Network. I'm Marco Meglio.

Newly announced interim data from the phase 2 FORWARD-53 study (NCT04906460) showed that treatment with Wave Life Sciences’ WVE-N531, an investigational antisense oligonucleotide, resulted in substantial dystrophin expression among boys with Duchenne muscular dystrophy (DMD) amenable to exon 53 skipping. The company expects to complete the trial in the first quarter of 2025, and anticipates using feedback from regulators to provide guidance for an accelerated approval.A total of 11 enrolled boys amenable to exon 53 skipping received 10 mg/kg infusions of WVE-N531 every 2 weeks (Q2W), with muscle biopsies taken after 24 and 48 weeks of dosing. At 24 weeks, interim results revealed a mean absolute muscle content-adjusted dystrophin expression of 9.0% (range, 4.6%-13.9%) and a mean absolute unadjusted dystrophin expression that was 5.5% of normal (range, 3.3%-8.3%), as measured by Western Blot. Notably, 89% of ambulatory participants (n = 10) achieved muscle content-adjusted dystrophin levels of at least 5%.

Newly published data from a post-hoc analysis of a phase 2 investigator-initiated trial (NCT03456882) showed that treatment with Revalesio’s RNS60, an anti-inflammatory and cytoprotective agent, resulted in beneficial impacts on survival and slowing the decline of respiratory function in patients with amyotrophic lateral sclerosis (ALS). Overall, the therapy was most successful in those with lower neurofilament light (NfL) and Monocyte Chemoattractant Protein-1 (MCP-1) levels at study entry, suggesting this could be a subgroup to target in future studies assessing RNS60’s effect on survival.Published in Brain, Behavior, and Immunity, the double-blind, placebo-controlled study randomly assigned 147 patients with ALS to either RNS60 (n = 74) or placebo (n = 73) for 24 weeks. Over a mean duration follow-up of 2.8 years, long-term median survival was 6 months longer in the RNS60 group (P = .0519) over placebo. During that time, the number of deaths was 40 (54.1%) in the group randomized to RNS60 and 46 (63.0%) in the group randomized to placebo.

Capricor has announced that following recent meetings with the FDA, the company intends to submit a biologics license application (BLA) later this year seeking full approval for its investigational agent deramiocel as a new treatment for patients with Duchenne muscular dystrophy (DMD) cardiomyopathy.Also known as CAP-1002, the treatment consists of allogeneic cardiosphere-derived cells, a population of stromal cells that have been shown in preclinical and clinical studies to exert potent immunomodulatory, antifibrotic and regenerative actions in dystrophinopathy and heart failure. In its announcement, Capricor claimed it was using data from the phase 2 HOPE-2 (NCT03406780) and HOPE-2 open label extension (OLE) trials as supplementary evidence, as well as combined data from cohorts A and B of the phase 3 HOPE-3 trial (NCT05126758). Notably, the company does not intend to unblind Cohort A from HOPE-3 at this time, which was expected to occur in the fourth quarter of 2024.

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