Neflamapimod Improved Motor Function and Reduced Cognitive Decline in Dementia With Lewy Bodies

In the AscenD-LB phase 2 trial (NCT04001517) treatment of mild-to-moderate dementia with Lewy bodies (DLB) with neflamapimod (EIP Pharma, Boston,MA) significantly improved motor function and reduced cognitive decline. 

After 16 weeks of treatment, neflamapimod vs placebo resulted in a 65% reduction in the worsening of dementia, as measured with the Clinical Dementia Rating scale Sum of Boxes (CDR-SB; P=.024). On the Timed Up and Go test, a measure of motor function, those treated with neflamapimod had a mean improvement of 1.4 seconds compared with placebo (P=.044 for 40 mg twice daily and P=.024 for 40 mg three times daily, both using mixed model for repeated measures analyses). 

Approximately half of participants in both placebo and treatment groups had evidence of concomitant Alzheimer disease (AD)-like tauopathy, typically found in one-third of people with DLB. Among those without evidence of AD-like tauopathy, neflamapimod had higher efficacy with effect size of AD-like tauopathy ranging from 0.56 to 0.78, suggesting effects of neflamapimod are driven by DLB-specific pathology, namely basal forebrain cholinergic dysfunction.

"The final results of the AscenD-LB study are extremely exciting for patients with DLB, caregivers and clinicians as we may be looking at the first DLB treatment that modifies the underlying disease", said Dr. James Galvin, professor of Neurology and director of the Lewy Body Dementia Research Center of Excellence at the University of Miami Miller School of Medicine. "Combined with the scientific studies that preceded the clinical study, the results suggest that neflamapimod has the potential to change the course of the disease and significantly improve function and quality of life in patients with DLB. In addition, AscenD-LB has also advanced the field by increasing our understanding of the disease and the tools we can use to measure drug treatment effects in clinical trials in dementia with Lewy bodies."

In this 16-week multisite international proof-of-concept study, 91 participants were randomly assigned 1:1 to receive 40 mg neflamapimod or placebo. Dosing was weight based with those weighing less than 80 kg receiving twice daily doses and those 80 kg or more receiving doses three times daily. Evidence of AD-like tauopathy was considered as a plasma level of less than 2.2 pg/mL ptau-181.

These data were presented at the Clinical Trials in Alzheimer Disease conference held in Boston, MA November 9-12, 2021.