Small Molecule Kinase Inhibitor Slowed Clinical Progression in People with Dementia with Lewy Bodies
Treatment with neflamapimod (CervoMed, Boston, MA) —an investigational, orally administered small molecule kinase inhibitor—was associated with significant improvements in clinical and biomarker outcomes in people with dementia with Lewy bodies (DLB), according to findings from the extension-phase analyses of the phase 2b RewinD-LB trial (NCT05869669), which were presented at the 18th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference. Treatment benefits were more pronounced for participants who received a reformulated capsule batch and had biomarker measures associated with the absence of Alzheimer disease (AD) copathology.
RewinD-LB included an initial 16-week randomized, double-blind, placebo-controlled phase followed by a 32-week open label extension (OLE). The trial evaluated oral neflamapimod 40 mg 3 times daily in 159 participants with DLB across 43 sites in the United States, United Kingdom, and the Netherlands. During the randomized phase, participants received neflamapimod or placebo in capsules later determined (DP Batch A) to have lower-than-expected bioavailability, and no significant benefit on the primary end point was observed. In the extension phase, a subset of participants received a reformulated capsule batch (DP Batch B), which was shown to achieve target plasma levels. Researchers compared across-patient and within-patient outcomes DP Batch A and DP Batch B, while also evaluating outcomes for a subgroup of participants with AD copathology as determined by plasma phosphorylated tau-181 (ptau-181). The primary end point of the study was change in Clinical Dementia Rating–Sum of Boxes (CDR-SB).
Key results from the OLE phase include the following:
- At week 16 in all participants in the extension phase, mean CDR-SB worsening was 52% lower with DP Batch B vs DP Batch A, and 82% lower in those without AD copathology.
- At week 32, there was a mean CDR-SB worsening of 1.73 points with DP Batch A vs 0.53 points with DP Batch B (65% reduction) for all participants, while those without AD copathology had a mean CDR-SB worsening of 1.44 points with DP Batch A vs 0.16 points with DP Batch B (89% reduction).
- Among participants who switched from placebo in the initial phase to DP Batch B in the extension, DP Batch B treatment was associated with a 1.12-point improvement on CDR-SB vs placebo over 16 weeks (P=.005) and a 0.82-point improvement on Alzheimer’s Disease Cooperative Study–Clinical Global Impression of Change (ADCS-CGIC) (P=.004).
- In the subgroup without AD copathology, DP Batch B reduced the risk of clinical progression (≥1.5-point increase in CDR-SB) by 75% over 16 weeks vs placebo and increased projected median time to progression to an estimated 1.5 years vs 16 weeks with placebo.
- During the 32-week OLE, median change in plasma GFAP with DP Batch B was -16.0 pg/mL (IQR, -35 to +6.7; P<.0001), and in within-subject comparisons, GFAP change was 23.5 pg/mL lower during DP Batch B treatment than during prior placebo exposure (P=.016).
- Neflamapimod was generally well tolerated over 48 weeks, with discontinuation for liver enzyme elevation in 2.5% of neflamapimod recipients in the initial phase and 1.3% in the OLE, and all events were reversible and not associated with bilirubin elevation.
Source: CervoMed. CervoMed announces late-breaking data at the 18th CTAD conference demonstrating neflamapimod significantly slows clinical progression in dementia with lewy bodies. CervoMed News & Events. Published December 4, 2025. Accessed December 11, 2025. https://ir.cervomed.com/news-releases/news-release-details/cervomed-announces-late-breaking-data-18th-ctad-conference