Phase 2 results demonstrated proof-of-concept for treatment with neflamapimod, suggesting the need for a phase 3 study in the coming future.
EIP Pharma announced that the phase 2 AscenD-LB study (NCT04001517), which assessed neflamapimod in patients with mild-to-moderate dementia with Lewy bodies (DLB), met its primary end point of demonstrating an improvement in cognition as assessed by the Neuropsychological Test Battery (NTB).1
Patients who received neflamapimod 3 times daily (TID) demonstrated significant improvement on the NTB compared to those who received neflamapimod twice daily (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.
“Not only was the prespecified primary outcome met for the 3 times daily dose arm but supportive trends were observed in several of the secondary outcomes, setting the stage for more extensive testing,” Jeffrey Cummings, MD, ScD, Joy Chambers-Grundy Professor of brain science, and director, Chambers-Grundy Center for Transformative Science, UNLV School of Integrated Health Sciences, said in a statement.
There were no patients who discontinued the study due to drug-related adverse events (AEs). In total, there were 10 early treatment discontinuations, 4 of which were from intercurrent mental illness (2 in each placebo and neflamapimod BID recipients) and 6 from withdrawal of consent and/or disease worsening (2 in placebo and 4 in neflamapimod BID).
Researchers noted that there were 4 serious AEs (SAEs) reported in the placebo group and 3 in neflamapimod BID recipients, all of which were considered unrelated to the study drug administration. Notably, neflamapimod TID recipients did not report any SAEs or early treatment discontinuations.
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 ≤80 kg were given BID, as opposed to those who weighed >80 kg who were placed in the TID group. 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.
According to EIP, the ability to demonstrate proof-of-concept in a phase 2 setting will allow them to advance the development of neflamapimod into a phase 3 study. The company did not announce a timetable for when that may occur.
"The exciting results of the Phase 2 AscenD-LB study showing benefit of the investigational drug neflamapimod for cognition in DLB will bring hope to patients and their caregivers," Stephen Gomperts, MD, PhD, director, Lewy Body Dementia Unit, and assistant professor of neurology, Massachusetts General Hospital, said in a statement. “If these findings are confirmed in a phase 3 study, the potential impact for patients with DLB will be significant.”
Neflamapimod was granted fast track designation by the FDA for the treatment of DLB in November 2019. At the time, the company also announced results of the REVERSE-SD study that examined neflamapimod in early stage Alzheimer disease (AD).2
The randomized, double-blind, placebo-controlled, proof-of-concept study included 161 participants with early-stage AD who were randomly assigned to receive neflamapimod 40-mg or placebo twice daily for 24 weeks. While the study met its target engagement and demonstrated a statistically significant reduction in phosphorylated tau and tau levels in the cerebrospinal fluid (CSF), it failed to meet its primary end point of improved episodic memory as measured by the Hopkins Verbal Learning Test.
In addition to being accepted as a late-breaking abstract, the full results of AscenD-LB will be shared on November 7, 2020 during an oral presentation at the 13th Clinical Trials in Alzheimer’s Disease (CTAD) meeting.
Cummings, on the importance of these results, commented, “There are no approved treatments for DLB, the second most cause of neurodegenerative dementia, and there is an urgent need to find therapies for this and related disorders such as Alzheimer’s disease.”