“Significant unmet need exists for improved Alzheimer’s treatments which is why we are so encouraged by these data demonstrating neflamapimod’s potential to improve memory function in patients with Alzheimer’s disease,” John Alam, MD, EIP Pharma’s CEO, said in a press release. “We look forward to reporting top-line results of the recently initiated REVERSE-SD Phase 2b clinical study in the second half of 2019.”
Based on the findings, the company is now recruiting for the Phase 2b trial (NCT03402659) to confirm the positive effects of neflamapimod in patients with mild Alzheimer’s disease. The trial will enroll about 150 participants who will be randomized to receive either placebo or 40 mg pills of neflamapimod twice daily for six months. The primary objective is episodic memory improvement, while secondary endpoints include cognitive and dementia tests and cerebrospinal fluid biomarkers.
EIP Pharma’s neflamapimod specifically targets amyloid-beta and tau proteins. It is a brain-penetrant oral small molecule that inhibits the enzyme p38-alpha, a critical player in the dysfunctional nerve cell connections that cause memory deficits in Alzheimer’s disease.
Data from the Phase 2a trial were reported in the study, “An exploratory clinical study of p38α kinase inhibition in Alzheimer’s disease,” published in the Annals of Clinical and Translational Research.
The trial (NCT02423122) enrolled 16 patients with early Alzheimer’s disease, randomized to receive either 40 mg or 125 mg of neflamapimod twice daily for three months.
To evaluate treatment effectiveness, positron emission tomography (PET) scans assessed brain amyloid plaque load, and episodic memory function was assessed using neuropsychological tests.
Neflamapimod significantly improved episodic memory (memory regarding personal facts and experiences), namely immediate recall and delayed recall, at evaluations performed at day 28 of treatment and at the end of the trial, at day 84. Memory improvement progressively increased during the trial, reaching its maximum effect at the end of the three-month treatment.
Plasma drug concentrations reflected the change in episodic memory. At the higher dose of neflamapimod, the beneficial effects were stronger.
No correlation was seen between improvements in episodic memory function and reduction in brain amyloid plaque load, with only four patients displaying a significant reduction in amyloid plaque burden.
“Neflamapimod demonstrated a robust signal of efficacy on measures of episodic memory in this study,” said Philip Scheltens, MD, PhD, first author of the study. “Through conducting the REVERSE-SD study we hope to definitively confirm the effects on episodic memory seen in our Phase 2a study in a placebo-controlled study.”
Scheltens is a professor at the VU Medical Center in Amsterdam, where the study was conducted, and is also the principal investigator of the upcoming REVERSE-SD Phase 2b trial.