FDA Feedback Provides Clarity for Phase 3 Trial of Neflamapimod in Dementia With Lewy Bodies

According to a recent company update, the FDA has shared written feedback aligning on key aspects of CervoMed’s proposed phase 3 trial for neflamapimod, an investigational oral therapy for the treatment of patients with dementia with Lewy bodies (DLB), to support a potential new drug application (NDA) submission. The company anticipates receiving feedback from other global regulatory authorities in the coming months and plans to provide additional details on the phase 3 trial design in early 2026 following these interactions.¹

Based on the feedback from the agency, the company plans to initiate a single, global, randomized, double-blind, placebo-controlled phase 3 trial investigating the efficacy and safety of neflamapimod in approximately 300 patients with DLB who meet consensus clinical criteria in the second half of 2026. The study will randomize participants 1:1 to receive either oral neflamapimod or placebo for 32 weeks, followed by a neflamapimod-only extension for 48 weeks.

CervoMed noted that the study will exclude patients with historical evidence of Alzheimer disease (AD) co-pathology based on brain imaging or cerebrospinal fluid analysis. The trial will further select participants without AD co-pathology using a validated blood plasma test; individuals with plasma ptau181 levels of at least 21.0 pg/mL at screening will be excluded.

"We are pleased to have reached alignment with the FDA on a registration path and key aspects of our planned Phase 3 clinical trial for neflamapimod in DLB. This regulatory alignment validates the strength of the neflamapimod clinical development program, and the quality of evidence generated to date. DLB is a devastating disease with no approved therapies, and we believe neflamapimod has the potential to meaningfully advance care for patients and families as a first-in-class treatment for this condition," Marwan Sabbagh, MD, FAAN, FANA, behavioral neurologist at Barrow Neurological Institute and nonexecutive director at CervoMed, told NeurologyLive^® in a recent interview.

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The primary end point of the planned phase 3 trial will be change in global cognition and function, as measured by the Clinical Dementia Rating–Sum of Boxes (CDR-SB), consistent with the primary end point used in the company’s recently completed phase 2b RewinD-LB trial (NCT05869669) in DLB. Secondary end points will include the percentage of participants with a CDR-SB increase greater than 1.5 points and additional validated measures of cognitive and motor function. The study will also assess biomarkers of neurodegeneration, including glial fibrillary acidic protein, to support regulatory review and clinical interpretation.

"We are highly encouraged that critical elements of the planned Phase 3 clinical trial design are consistent with our previously completed Phase 2a and Phase 2b studies, which demonstrated positive treatment effects of neflamapimod in patients living with DLB. As such, we believe this Phase 3 trial, the first ever targeting cognitive and functional decline in DLB, is well-positioned to achieve its primary objective," Sabbagh said. "Given the high unmet need in DLB, we are excited to start this first-ever Phase 3 study in DLB, in the second half of 2026. By addressing the underlying biology rather than symptoms alone, neflamapimod has the potential to improve cognition and function in DLB and fundamentally change how this devastating disease is treated."

Earlier this year, CervoMed announced positive results from RewinD-LB, demonstrating that treatment with neflamapimod significantly improved the primary outcome measure and reduced neurodegenerative biomarkers in patients with DLB. RewinD-LB was a randomized, 16-week, double-blind, placebo-controlled trial of 159 patients with DLB, followed by an open-label, 32-week extension phase. Similar to the planned phase 3 trial, patients with AD co-pathology, as assessed by plasma p-tau 181 levels, were excluded from the study.²

In the RewinD-LB trial, 2 capsule batches were used: the initial “Old Capsules” (NFMD/A), which failed to reach target plasma levels, and the later “New Capsules” (NFMD/B), which achieved the desired concentrations. In the initial 16-week phase, the old capsules group showed between-group differences of –0.53 (P = 0.10; linear mixed-effects model) on CDR-SB, the primary end point, relative to placebo. During the first 16 weeks of the extension phase, the new capsule formulation outperformed the old formulation on CDR-SB, with between group differences of –0.58 (P = .024).

The phase 2 AscenD-LB study (NCT04001517), which assessed neflamapimod in patients with mild-to-moderate DLB, met its primary end point of demonstrating an improvement in cognition as assessed by the Neuropsychological Test Battery (NTB). AscenD-LB was a double-blind, placebo-controlled, proof-of-concept study that randomized patients 1:1 to receive 40-mg neflamapimod capsules or matching placebo capsules over a 16-week period. Patients who weighed at most 80 kg were given neflamapimod twice daily (BID), as opposed to those who weighed more than 80 kg who were placed in theneflamapimod 3 times daily (TID) group.³

As patients were evaluated on NTB, secondary analyses included additional composites built from a subset of tests in the NTB, 10-item Neuropsychiatric Inventory, Timed Up and Go test, and the Clinical Dementia Rating scale Sum of Boxes.Patients who received neflamapimod TID demonstrated significant improvement on the NTB compared to those who received neflamapimod BID or placebo (effect size d = 0.52; P = .015). Furthermore, statistically significant improvements (P <.05) or trends (P <.01) were evident on multiple secondary clinical end points.

"In our Phase 2a (ASCEND-LB) and Phase 2b (REWIND-LB) clinical studies, neflamapimod demonstrated reproducible improvements in cognition and function, with supportive biomarker changes, and a favorable safety profile, particularly in patients with DLB and a low likelihood AD co-pathology," Sabbagh told NeurologyLive. "Collectively, these findings underscore the therapeutic promise and scientific validity of neflamapimod as a potential treatment for DLB and other degenerative brain disorders. We are encouraged by the body of data generated to date and believe it further de-risks the development program as we move forward into a planned Phase 3 study."

REFERENCES
1. CervoMed Announces Alignment with FDA on Registration Path for Neflamapimod in Dementia with Lewy Bodies. News release. CervoMed. November 4, 2025. https://ir.cervomed.com/news-releases/news-release-details/cervomed-announces-alignment-fda-registration-path-neflamapimod
2. CervoMed Announces New Data from Phase 2b Trial Demonstrating Neflamapimod's Potential as a Treatment for Dementia with Lewy Bodies. News release. CervoMed. October 8, 2025. Accessed November 4, 2025. https://ir.cervomed.com/news-releases/news-release-details/cervomed-announces-new-data-phase-2b-trial-demonstrating?mobile=1
3. EIP Pharma announces positive phase 2 results for neflamapimod in mild-to-moderate dementia with Lewy bodies (DLB). News release. EIP Pharma. October 6, 2020. Accessed November 5, 2025. https://www.prnewswire.com/news-releases/eip-pharma-announces-positive-phase-2-results-for-neflamapimod-in-mild-to-moderate-dementia-with-lewy-bodies-dlb-301146415.html​