Positive AscenD-LB Trial Outcomes for Neflamapimod in Lewy Body Dementia

On February 12, 2024, CervoMed Inc., a clinical-stage company dedicated to the development of treatments for brain degenerative diseases, announced the publication of data from the AscenD-LB Phase 2a trial on the treatment of dementia with Lewy bodies (DLB) using neflamapimod. This data is now available in the Journal of Prevention of Alzheimer’s Disease (JPAD) under the title, "Phase 2a learnings incorporated into RewinD-LB, a Phase 2b clinical trial of neflamapimod in dementia with Lewy bodies."

John Alam, MD, CEO of CervoMed, remarked on the significance of the EEG and MRI results, which advance neflamapimod into late-stage development as a potential treatment for DLB. Despite there being no currently approved treatments for DLB, the promising data bolsters the ongoing RewinD-LB Phase 2b trial, aiming to target the expansion of this therapy into the market. This trial’s design incorporates learnings from the Phase 2a study, adding robustness to its methodology. The RewinD-LB trial is set to complete enrollment in the first half of 2024, with primary efficacy results expected in the second half of 2024.

Notably, the newly published JPAD manuscript summarises several key findings:

1.It presents an integrated analysis of neflamapimod at 40mg, administered three times a day (TID) versus placebo, across all endpoints in the AscenD-LB Phase 2a trial. This includes both overall patient populations (mixed with some Alzheimer's disease (AD) co-pathology) and those solely with pure DLB. Data indicated that patients with pure DLB exhibited a significantly higher response to neflamapimod compared to the overall patient population. Additionally, pure DLB patients improved in working memory as measured by the International Shopping List Test (ISLT) recognition.

2.EEG results from the AscenD-LB trial revealed that neflamapimod treatment led to improvement in beta functional connectivity (p=0.01 vs. placebo TID), a potential distinguishing factor between DLB and AD.

3.Previous Phase 2a results in AD indicated that neflamapimod treatment led to increased volume and functional connectivity of the basal forebrain, particularly the nucleus basalis of Meynert (NbM). After 12 weeks of treatment, the NbM volume increased by an average of 3.1% compared to baseline (p=0.03), along with an 11% enhancement in functional dynamic connectivity between the NbM and deep gray matter (DGM) (p=0.04).

The key learnings from AscenD-LB are incorporated into the RewinD-LB Phase 2b trial, which now utilizes a single dose regimen of neflamapimod 40mg TID, focusing on patients with pure DLB and the CDR-SB as the primary endpoint. Further effects on structural and functional brain atrophy will be evaluated using MRI in a subgroup of 40 patients.

The RewinD-LB Phase 2b study is a 16-week, randomized, double-blind, placebo-controlled trial involving up to 160 patients with prodromal or mild dementia due to DLB, excluding those with Alzheimer's disease-related co-pathology. Participants completing the initial 16 weeks on a placebo will be eligible for an additional 32 weeks of open-label neflamapimod treatment. Primary and secondary endpoints in the study include changes in CDR-SB, TUG test, cognitive test battery, and CGIC. Funded by a $21 million grant from the National Institutes of Health's National Institute on Aging (NIA), enrollment across 41 sites in the U.S., U.K., and Netherlands is active.

CervoMed Inc. is focused on treating age-related neurological disorders and is currently advancing neflamapimod, a unique small molecule designed to inhibit p38MAP kinase alpha (p38a), a potential therapeutic avenue for diseases like DLB.