Biogen plans regulatory filing at FDA for aducanumab in Alzheimer's disease based on new phase III analyses.

Biogen announced that, after consulting with the FDA, Biogen plans to pursue regulatory approval for aducanumab, an investigational treatment for early Alzheimer�s disease (AD).

The Phase III EMERGE Study met its primary endpoint showing a significant reduction in clinical decline, and Biogen believes that results from a subset of patients in the Phase III ENGAGE Study who received sufficient exposure to high dose aducanumab support the findings from EMERGE. Patients who received aducanumab experienced significant benefits on measures of cognition and function such as memory, orientation, and language. Patients also experienced benefits on activities of daily living including conducting personal finances, performing household chores such as cleaning, shopping, and doing laundry, and independently traveling out of the home.

If approved, aducanumab would become the first therapy to reduce the clinical decline of Alzheimer�s disease and would also be the first therapy to demonstrate that removing amyloid beta resulted in better clinical outcomes.

The decision to file is based on a new analysis, conducted by Biogen in consultation with the FDA, of a larger dataset from the Phase III clinical studies that were discontinued in March 2019 following a futility analysis. This new analysis of a larger dataset that includes additional data that became available after the pre-specified futility analysis shows that aducanumab is pharmacologically and clinically active as determined by dose-dependent effects in reducing brain amyloid and in reducing clinical decline as assessed by the pre-specified primary endpoint Clinical Dementia Rating-Sum of Boxes (CDR-SB). In both studies, the safety and tolerability profile of aducanumab was consistent with prior studies of aducanumab.

Based on discussions with the FDA, the Company plans to file a Biologics License Application (BLA) in early 2020 and will continue dialogue with regulatory authorities in international markets including Europe and Japan. The BLA submission will include data from the Phase 1/1b studies as well as the complete set of data from the Phase III studies..

Comment: A point of confusion is the inconsistency between EMERGE and ENGAGE trials, which Biogen emphasized were identically designed. ENGAGE participants who received the higher dose of aducanumab, the dose on which Biogen is depending on for its approval application, performed worse than placebo-treated patients on the study's main cognitive test.That is opposite to what happened in EMERGE, in which aducanumab-treated patients experienced a 23% reduction in cognitive decline compared to those on placebo.