FDA CRL - Mapi-Pharma Ltd.

The U.S. Food and Drug Administration (FDA) issued a Complete Response Letter (CRL) to Mapi Pharma Ltd. for its New Drug Application (NDA 218223) for glatiramer acetate epi. The FDA determined that the application cannot be approved in its current form due to significant deficiencies in both product quality and clinical/statistical data. The Phase 3 trial (Study Mapi GA Depot Phase III — 001) failed to provide interpretable or persuasive findings of efficacy for treating relapsing forms of multiple sclerosis (RMS) and did not meet the evidentiary standard for substantial effectiveness. Additionally, the company failed to establish a necessary "scientific bridge" to Copaxone, crucial for relying on its safety and effectiveness findings. Major issues with the clinical trial centered on the quality and integrity of relapse data. The relapse determination methodology was unacceptable, lacking auditable documentation for confirmation, utilizing an unacceptably prolonged 2-week evaluation window post-symptom onset, and suffering from potential confirmation bias due to unblinded investigators and EDSS raters. Furthermore, the trial lacked an independent Relapse Adjudication Committee. To address these deficiencies, Mapi Pharma Ltd. is required to conduct a new, adequate, and well-controlled study to demonstrate a significant treatment effect with rigorously measured outcomes. The FDA strongly recommends seeking the Division’s feedback on any future study protocol.