CAMBRIDGE, Mass., March 7, 2018 /PRNewswire/ -- EIP Pharma LLC (www.eippharma.com), a CNS-focused therapeutics company, today announced that the results from a 3-month Phase 2a clinical study with neflamapimod, a brain-penetrant oral small molecule that inhibits the intra-cellular enzyme p38 MAP kinase alpha (p38α), in patients with early Alzheimer's disease have been published in the Annals of Clinical and Translational Neurology. Based on the findings from phase 2a, the company has initiated a 6-month phase 2b clinical study (REVERSE-SD) designed to evaluate neflamapimod's activity in reversing synaptic dysfunction ("SD"), as assessed by tests of episodic memory in patients with mild Alzheimer's disease.
"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," said John Alam, CEO of EIP Pharma. "We look forward to reporting top-line results of the recently initiated REVERSE-SD Phase 2b clinical study in the second half of 2019."
"Neflamapimod demonstrated a robust signal of efficacy on measures of episodic memory in this study," said Professor Philip Scheltens of the VU Medical Center in Amsterdam (Netherlands), first author of the publication and global principal investigator for REVERSE-SD, "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."
The paper, titled 'An exploratory clinical study of p38α kinase inhibition in Alzheimer's disease' (https://doi.org/10.1002/acn3.549), reports the results of the Phase 2a study with neflamapimod (NCT02423122), in which 16 patients with early Alzheimer's disease were enrolled. The major clinical finding was statistically significant improvement in episodic memory function with neflamapimod, as assessed by immediate recall (p=0.001) and delayed recall (p<0.001) composites of the relevant components of the Wechsler Memory Scale (WMS). The improvement was progressive over the 3-months of treatment and at the end of treatment the within-subject treatment Effect Size was in medium to large range: 0.59 for immediate recall and 0.67 for delayed recall. In addition, individual subject plasma drug concentration profiles were highly significantly positively correlated with the change in combined WMS immediate and delayed recall (p < 0.0001, r2 = 0.70). The primary biomarker endpoint in the study was change in brain amyloid plaque load by quantitative dynamic amyloid PET scanning, with 4 of the 16 patients meeting pre-defined responder criteria for a significant reduction in brain amyloid plaque load between baseline and month 3 PET scans. No correlation was evident between improvement in episodic memory function and reduction in brain amyloid plaque load.
150 patients with mild Alzheimer's disease will be randomized on a double-blind basis to placebo or 40 mg of neflamapimod twice daily for 24 weeks. Inclusion criteria include Clinical Dementia Rating scale (CDR) 0.5 or 1.0 with documented memory deficit, MMSE 20 to 28, and positive AD-related cerebrospinal fluid biomarkers. The primary endpoint will be episodic memory, with secondary endpoints including CDR-SB, MMSE, and CSF biomarkers. Further details are available at clinicaltrials.gov: https://clinicaltrials.gov/ct2/show/NCT03402659.
About neflamapimod (VX-745) and p38 MAPKα
Neflamapimod (formerly VX-745) 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 and/or amyloid beta induced synaptic toxicity, including the impairment of synaptic function (specifically synaptic plasticity). Synaptic plasticity is known to be a major driver of the development of deficits in learning and memory formation that are defining characteristics of Alzheimer's disease. Further information on neflamapimod and p38a was published in November 2017 as a review in the Journal of Prevention of Alzheimer's Disease (JPAD): https://doi.org/10.14283/jpad.2017.41
Neflamapimod was discovered by Vertex Pharmaceuticals Incorporated and licensed by EIP Pharma LLC in 2014.
About EIP Pharma LLC
EIP Pharma LLC (www.eippharma.com) is a private, Cambridge, MA-based company advancing CNS-focused therapeutics for improved patient benefit. For more information please visit www.eippharma.com.
SOURCE EIP Pharma LLC