BOSTON, Nov. 7, 2019 /PRNewswire/ --EIP Pharma, Inc. (www.eippharma.com), a CNS-focused therapeutics company, today announced that the REVERSE-SD study of neflamapimod in early-stage Alzheimer's disease met its secondary objectives of target engagement and proof-of-mechanism demonstrating statistically significant reductions relative to placebo in cerebrospinal fluid (CSF) levels of phospho-tau and tau, the major markers of neurodegeneration and axonal damage. The study did not meet its primary objective of improving episodic memory at the end of the study period at week 24, as measured by Hopkins Verbal Learning Test (HVLT) and secondarily, the Wechsler Memory Scale (WMS) immediate and delayed recall. In pre-specified pharmacokinetic-pharmacodynamic (PK-PD) analyses, positive trends relative to placebo on both HVLT and WMS were evident in neflamapimod-treated patients whose plasma drug concentrations were in the highest quartile within the study. The efficacy and safety data from the study will be presented by the principal investigator of the study, Professor Philip Scheltens of the VU Medical Center in Amsterdam, Netherlands, at the Clinical Trials in Alzheimer's Disease (CTAD) meeting in San Diego on Thursday, December 5, 2019 at 11:45 AM.
"The CSF biomarker results are compelling, and support target engagement and proof-of-mechanism," said Professor Philip Scheltens of the VU Medical Center in Amsterdam, and the principal investigator of the study. "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."
About the REVERSE-SD Study In the REVERSE-SD study, 161 patients with early-stage Alzheimer's disease (AD) were enrolled at 38 sites in the Czech Republic (5 sites), Denmark (3 sites), Netherlands (3 sites), United Kingdom (11 sites) and USA (16 sites); and were randomized 1:1 to receive neflamapimod 40 mg capsules or matching placebo capsules twice daily with food for 24 weeks. Inclusion criteria were as follows: aged 55 to 85, with CDR-Global score of 0.5 or 1.0; CDR memory sub-score of at least 0.5; MMSE score of 20 to 28, inclusive; positive biomarker for AD, as defined by CSF Aβ1-42 <1000 pg/mL and phospho-tau/Aβ1-42 >0.24 in the Roche Eclesys® immunoassay; receiving either no AD-specific therapy or on a stable dose monotherapy (either cholinesterase inhibitor or memantine; dual therapy excluded).
Efficacy data will be presented at the CTAD meeting in December 2019. Neflamapimod was well tolerated with only 2 discontinuations (vs. 2 in placebo) for adverse events, one for nausea and one for diagnosis of myeloma. There were two Serious Adverse Events (SAEs) reported in neflamapimod patients (vs. three in placebo), hypokalemia and myeloma; both considered unrelated. The most common adverse events were upper respiratory tract infection (5% neflamapimod, 8% placebo), headache (5%, 6%) falls (6%, 4%), diarrhea (5%, 2%), post lumbar puncture syndrome (4%, 4%), vomiting (3%, 4%), depressed mood (3%, 4%), and fatigue (1%, 5%). One subject in the neflamapimod arm (vs. none in the placebo arm) developed liver enzyme (ALT, AST) elevation to three times upper limit of normal; this patient's liver enzyme elevation started resolving during one additional week of dosing, and then the subject withdrew from the study.
About neflamapimod Neflamapimod is a brain-penetrant, oral small molecule that inhibits the intra-cellular enzyme p38 MAP kinase alpha (p38α). P38α, which is expressed in neurons under conditions of stress and disease, plays a major role in inflammation-induced synaptic toxicity, leading to impairment of synaptic function. Synaptic dysfunction is known to be a major drive of the deficits in cognitive function that are defining characteristics of many CNS diseases. In addition to the Reverse-SD trial neflamapimod is currently being studied in separate Phase 2 trials in patients with dementia with Lewy bodies and with Huntington's disease who have evidence of cognitive dysfunction.
About EIP Pharma Inc EIP Pharma, Inc. is a private, Boston, MA-based company advancing CNS-focused therapeutics to benefit patients with neurodegenerative diseases.