Lewy Body Dementia Drug Neflamapimod Wins Fast Track Designation From FDA

Philip Scheltens, MD, PhD

EIP Pharma announced that neflamapimod has been granted fast track designation by the FDA for the treatment of dementia with Lewy bodies.¹ Additionally, they announced the results from the REVERSE-SD study that examined neflamapimod in early stage Alzheimer disease (AD).²

A phase 2, double-blind, placebo-controlled study (AscenD-LB) of neflamapimod in dementia with Lewy bodies (DLB) is now recruiting, with a target enrollment of 80 participants (men and women, ³55 years) across 20 sites in the US and 2 in the Netherlands (NCT04001517). The proof-of-concept study is aimed at whether the drug can improve synaptic dysfunction in patients with DLB. Patients enrolled will be monitored over the 16-week trial, where they will be assessed on a study-specific Cognate Neuropsychological Test Battery (NTB) for the primary endpoint. Patients will be also be assessed for changes on a range of secondary outcomes, including change on International Shopping List Test score, quantitative EEG, and Clinical Dementia Rating Scale-Sum of Boxes.

To meet trial criteria, a patient must have a Mini-Mental State Examination (MMSE) score between 15 to 28 during screening, as well as no history of learning difficulties that may interfere with the ability to complete cognitive tests. Trial criteria exclusions include ongoing central nervous system (CNS) conditions, experiences with suicidal thoughts, drug or alcohol abuse in the previous 2 years, or participation in another study for an investigational drug less than 3 months prior.

According to EIP Pharma, neflamapimod is a “brain-penetrant, oral small molecule that inhibits the intracellular enzyme p38 MAP kinase alpha (p38α).” P38a can play a key role in inflammation-induced synaptic toxicity, which ultimately leads to impairment of synaptic function.

Data from the AscenD-LB trial is expected in the second half of 2020.

The company also announced findings from its phase 2 REVERSE-SD study (NCT03402659) in mild AD, which was recently completed.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 cerebrospinal fluid, it failed to meet its primary endpoint of improved episodic memory as measured by the Hopkins Verbal Learning Test.

"The CSF biomarker results are compelling, and support target engagement and proof-of-mechanism," principal investigator Professor Philip Scheltens, of the VU Medical Center in Amsterdam, said in a statement.² "Combined with the efficacy signal at higher plasma drug concentrations, the results of the Reverse-SD study indicate that neflamapimod continues to show promise as Alzheimer's therapeutic and that a study of neflamapimod at higher doses in patients with early Alzheimer's disease is warranted."

Full results of the REVERSE-SD study will be presented at the upcoming CTAD meeting in San Diego.

References

1. EIP Pharma Announces U.S. FDA Grants Fast-Track Designation to Neflamapimod as a Treatment for Dementia with Lewy Bodies (DLB) [news release]. Boston, MA: EIP Pharma. November 7, 2019. prnewswire.com/news-releases/eip-pharma-announces-us-fda-grants-fast-track-designation-to-neflamapimod-as-a-treatment-for-dementia-with-lewy-bodies-dlb-300953421.html. Accessed: November 7, 2019.

2. EIP Pharma Announces Clinical Trial Results of REVERSE-SD, a Phase 2b Study of Neflamapimod in Early-stage Alzheimer's Disease [news release]. Boston, MA: EIP Pharma. November 7, 2019. prnewswire.com/news-releases/eip-pharma-announces-clinical-trial-results-of-reverse-sd-a-phase-2b-study-of-neflamapimod-in-early-stage-alzheimers-disease-300953422.html. Accessed: November 7, 2019.