CervoMed to Present Plasma Biomarker Data on Neflamapimod Effects in DLB at AAIC 2024

CervoMed Inc., a Boston-based clinical-stage company devoted to creating treatments for age-related neurological disorders, has released remarkable plasma biomarker data from its AscenD-LB Phase 2a trial of neflamapimod in patients with dementia with Lewy bodies (DLB). This data was showcased in a poster presentation at the Alzheimer's Association International Conference (AAIC) held in Philadelphia from July 28 to August 1, 2024.

John Alam, MD, Chief Executive Officer of CervoMed, emphasized the significance of plasma glial fibrillary acidic protein (GFAP) in assessing therapeutic impacts on DLB-specific disease processes. He pointed out that baseline data from the AscenD-LB trial reinforced the utility of this biomarker. The study established a clear link between plasma GFAP levels and dementia severity among DLB patients. Furthermore, growing evidence has highlighted the role of neflamapimod in influencing GFAP, suggesting its potential in addressing the underlying disease mechanism in early-stage DLB. Alam believes that these key insights from the AscenD-LB Phase 2a trial have optimized their ongoing RewinD-LB Phase 2b trial for success, with topline data expected by December 2024.

The ePoster titled "Neflamapimod treatment reduces plasma glial fibrillary acidic protein GFAP levels in patients with dementia with Lewy bodies (DLB) who do not have co-existing AD co-pathology," authored by John Alam and collaborators, is available on the conference portal. It discusses the effects of neflamapimod on plasma GFAP levels in both overall and early-stage DLB patient populations, drawing correlations to clinical outcomes.

Key findings from the presentation include:

1. Baseline plasma GFAP levels were highly correlated with baseline Clinical Dementia Rating Sum of Boxes (CDR-SB) scores and were significantly higher in patients with Alzheimer’s Disease (AD) co-pathology compared to those without.
2. In early-stage DLB patients, those in the placebo group saw a mean increase of 14.1 pg/mL in plasma GFAP, while those treated with neflamapimod experienced a mean reduction of 10.6 pg/mL, a statistically significant difference. In advanced DLB patients, the reduction in plasma GFAP was not statistically significant.
3. In early-stage DLB patients treated with neflamapimod, there was a meaningful correlation between GFAP reduction and clinical improvement, assessed by changes from baseline to week 16 in CDR-SB scores. This correlation was not observed in placebo recipients.

Recent advancements in the field suggest the use of plasma GFAP as a biomarker for the disease process in DLB. For example, a study from the Mayo Clinic demonstrated that patients with prodromal DLB had elevated plasma GFAP levels compared to healthy controls. This elevation seemed to reflect basal forebrain cholinergic system degeneration, a primary driver of early-stage DLB progression. Another study from the European Dementia with Lewy Bodies consortium found that plasma GFAP levels were associated with cognitive decline rates in DLB patients but not with CSF amyloid status, indicating that GFAP could be a valuable marker for DLB-specific processes.

The ongoing RewinD-LB Phase 2b study is a randomized, double-blind, placebo-controlled clinical trial examining the effects of oral neflamapimod in up to 160 patients with very mild or mild dementia due to DLB. The 16-week study allows patients to continue in an open-label phase for an additional 32 weeks. The primary endpoint is the change in the Clinical Dementia Rating Sum of Boxes, with secondary endpoints including the Timed Up and Go test, a cognitive test battery, and the Clinician’s Global Impression of Change. The study, funded by a $21 million grant from the National Institute on Aging, is being conducted across 43 sites in the United States, the United Kingdom, and the Netherlands. Enrollment was completed in June 2024, with topline primary efficacy results anticipated in December 2024.