CervoMed is developing neﬂamapimod for the treatment of central nervous system (CNS) disorders, including dementia with Lewy bodies (DLB), Alzheimer’s disease (AD) and stroke recovery.
RewinD-LB Phase 2b Clinical Trial in Dementia With Lewy Bodies
This is a randomized double-blind, placebo-controlled phase 2b study of neflamapimod in people living with DLB. This will confirm and expand upon the results from phase 2a. A total of 160 participants diagnosed with early-stage DLB will be randomized into the trial at clinical sites in the US, UK, and Netherlands.
Neflamapimod will be administered orally, 40 mg TID, with half the participants receiving matching placebo in the main study. All participants who complete the main study can continue into the open label portion of the study where all participants receive neflamapimod. Treatments will be administered for 12 weeks in the main study period, with a 36-week open label treatment extension in patients who complete the initial 12-week study treatment.
The primary objective is to confirm that neflamapimod, compared with placebo, improves dementia severity, as assessed by Clinical Dementia Rating Sum of Boxes (CDR-SB), in participants with DLB. Secondary objectives include studying safety of neflamapimod and confirming treatment effects on (1) motor function, specifically gait, as assessed by the Timed Up and Go test, (2) cognition, as assessed by a DLB-specific cognitive test battery, and (3) global rating of treatment effect, assessed by the ADCS-Clinician Global Impression of Change (CGIC).
Dementia With Lewy Bodies Trial, Phase 2a
CervoMed conducted a randomized double-blind, placebo-controlled clinical trial to investigate the effects of neﬂamapimod on reversing synaptic dysfunction and improving cognition in patients with mild-to-moderate dementia with Lewy Bodies (DLB). The trial, was conducted in the United States and Netherlands. Patients in this study had a diagnosis of DLB that corresponded to mild to moderate disease and received a stable dose of cholinesterase inhibitor therapy (>3 months). Results of the study were positive and neflamapimod showed significant positive effects, compared to placebo, on outcomes on the gold-standard dementia rating scale (Clinical Dementia Rating Sum of Boxes, CDR-SB) and on a measure of functional mobility (Timed Up and Go, TUG, test). In addition, at the higher of two doses evaluated in the study, neflamapimod showed significant improvement, compared to placebo, on a cognitive test battery that assessed attention and executive function. The results from this trial were published in the journal Nature Communications in September 2022. Additional results were published in the American Academy of Neurology journal in October 2023.
View the Nature publication at https://www.nature.com/articles/s41467-022-32944-3.
View the Neurology publication at https://n.neurology.org/content/early/2023/09/01/WNL.0000000000207755.
REVERSE-SD Phase 2b
REVERSE-SD was a double-blind, 6-month clinical trial designed to evaluate neﬂamapimod’s activity in reversing synaptic dysfunction, assessed by evaluating episodic memory in patients with early-stage Alzheimer’s disease. 161 patients were enrolled and randomized to either placebo or 40 mg of neﬂamapimod twice daily for 24 weeks. Results of the study showed target engagement of neflamapimod by demonstrating that neflamapimod reduced tau and ptau in cerebrospinal fluid (CSF) of AD patients. In this 6-month study, no discernable effect on cognition was seen on the overall population but a positive trend on cognition was observed in patients with the highest drug concentration level suggesting that a higher dose, either 40mg TID or 80mg BID, should be evaluated in subsequent longer duration trials to evaluate neflamapimod as a treatment to slow disease progression in AD.
Huntington’s Disease Trial, Phase 2a
Study Discontinued Due to COVID19 Restrictions
CervoMed conducted a double-blind, placebo-controlled, crossover clinical trial to investigate the effects of neﬂamapimod on reversing synaptic dysfunction and improving cognitive function in patients with early-stage Huntington’s disease. The study was conducted at one site in Cambridge, UK and was to evaluate 16 patients in the cross-over design. This study was discontinued because COVID19 restrictions impeded the completion of the trial, which because of its within-subject crossover design required patient participation in the study for at least nine months. There were no new safety signals identified.
Medicines for the Brain
Scientific data for neflamapimod has been published in certain medical journals and presented to the medical and scientific community at various medical meetings. Click below to access the data presentations.Presentations and Publications
"The positive effects in the AscenD-LB clinical study on cognitive and motor function demonstrate neflamapimod has potential as a treatment for patients with dementia with Lewy bodies. If these findings are confirmed in phase 2b and phase 3 clinical studies, neflamapimod could become the first approved therapy for this devastating disease. DLB is not only the second most common neurodegenerative dementia but is also associated with substantial reduction of patient quality of life and high caregiver burden."