Research led by Professor John-Paul Taylor, Theme Co-Lead for Dementia, Mental Health and Neurodegeneration at the NIHR Biomedical Research Centre (BRC): Newcastle and Professor of Translational Dementia Research at Newcastle University, has provided new evidence that an experimental drug could help slow the progression of dementia with Lewy bodies (DLB).

The findings have been published in two peer-reviewed journals, Alzheimer's Research & Therapy and Cells, and add to growing evidence that the drug neflamapimod may be able to target some of the underlying biological processes driving the disease.

A condition without a cure

DLB is the second most common form of progressive dementia after Alzheimer's disease, affecting millions worldwide. People living with the condition can experience problems with thinking and memory, visual hallucinations, movement difficulties similar to Parkinson's disease. There are no approved treatments for DLB in the United States or the European Union, and the current standard-of-care therapies only temporarily relieve symptoms.

CervoMed’s Phase 2b RewinD-LB clinical trial

CervoMed is a clinical-stage company developing treatments for age-related brain disorders. Its lead drug candidate, neflamapimod, is an oral small molecule targeting critical disease processes underlying degenerative disorders of the brain by inhibiting a key enzyme involved in neuroinflammation and neurodegeneration. Neflamapimod is currently in clinical development for the treatment of DLB, recovery after ischemic stroke, and primary progressive aphasia.

Neflamapimod was recently granted an Innovation Passport to enter the UK’s Innovative Licensing and Access Pathway (ILAP) for development in DLB. The ILAP, which focuses on potentially transformative investigational treatments that address unmet clinical needs, is designed to accelerate time to market and facilitate patient access to new medicines in the UK. It was also elected for inclusion in UK EXPERTS-ALS platform designed to prioritize promising treatments for Amyotrophic Lateral Sclerosis (ALS).

Professor Taylor was chief investigator of the RewinD-LB trial in the United Kingdom and first author of the Alzheimer’s Research & Therapy publication that reported results from the Phase 2b RewinD-LB clinical trial, which investigated neflamapimod in 159 people with DLB. While the trial did not meet its main outcome measure across all participants, researchers found encouraging signs that some patients benefited from treatment, particularly those without evidence of underlying Alzheimer's disease.

The study also identified biological changes that suggest the drug may be influencing disease-related processes in the brain. In an MRI substudy, participants receiving neflamapimod showed an increase in the volume of the right basal forebrain, an area particularly affected in DLB, compared with those receiving placebo.

A second publication in Cells explored how the drug works. Researchers found that neflamapimod blocks inflammatory signals in the brain that are thought to contribute to damage and cognitive decline in DLB. The findings provide further evidence that targeting neuroinflammation could be a promising approach for treating dementia.

Professor John-Paul Taylor said: “The placebo-controlled RewinD-LB data set, together with the Phase 2a results, provides encouraging evidence that neflamapimod may be an effective treatment for DLB and that further clinical evaluation is warranted. Taken together, these two important publications suggest that neflamapimod may be able to act on the underlying disease processes in DLB and make a meaningful difference for patients and caregivers who currently have limited therapeutic options.”

Dr John Alam, Founder and CEO of CervoMed said: “These publications demonstrate beneficial effects of neflamapimod on clinical endpoints and biomarkers of the underlying disease process that follow a consistent plasma drug-response relationship, with activity most evident at trough plasma concentrations of approximately 4 ng/mL or higher. We believe the alignment of clinical, biomarker, and imaging findings supports further development, particularly in patients without Alzheimer’s disease co-pathology, and reinforces the rationale for a 100 mg twice-daily dose using the new tablet formulation. This regimen is projected to achieve target trough concentrations in more than 90% of participants, providing more consistent drug exposure within the range associated with clinical activity in our prior clinical trials without substantially increasing peak concentrations or overall exposure.”

The research contributes to the NIHR BRC's mission of translating scientific discoveries into new approaches for diagnosing, treating and preventing dementia. As leaders in Lewy body disease, the BRC supports researchers such as Professor Taylor in developing and testing innovative treatments that could improve outcomes for people living with neurodegenerative diseases.

Further studies are planned to better understand which patients may benefit most from neflamapimod and to evaluate the treatment in larger clinical trials.

First published on CervoMed

Read A Phase 2b Randomized Clinical Trial of the Oral p38α Inhibitor Neflamapimod in Dementia with Lewy Bodies (DLB)

Read Targeting Pro-Inflammatory Interleukin-1 Beta Signaling to Modulate Neuroinflammatory Processes Associated with Cognitive Decline in Dementia with Lewy Bodies