Biogen and partner Eisai on Tuesday announced plans to file the experimental anti-amyloid beta antibody aducanumab for FDA approval early next year to treat patients with early Alzheimer's disease based on a new analysis of a larger dataset from the Phase III EMERGE and ENGAGE studies, which had been discontinued in March following a futility analysis. According to the companies, positive results of the new analysis were driven mainly by greater exposure to high-dose aducanumab in the larger dataset.
Biogen shares jumped as much as more than 40% on the news. CEO Michel Vounatsos said the company met with the FDA earlier this week, adding "we got clear support" from the agency. The drugmaker, which also reported its third-quarter results today, does not believe it needs to conduct additional trials of aducanumab before moving ahead.
The planned US filing could "potentially bring back to life a drug that had been completely left for dead," remarked RBC Capital Markets analyst Brian Abrahams. However, he suggested that "the viability of such a filing is unknown, given the mixed results. In our view, Biogen is somewhat desperate for growth drivers...so a change in narrative is badly needed."
The futility analysis earlier this year was based on data from patients who had completed 18 months in the EMERGE and ENGAGE trials through December 2018, representing 57% of patients enrolled in the first trial and 49% of patients in the second. After discontinuing the studies, Biogen reanalysed the data based on additional results from patients who had completed the trials between December and March. EMERGE met its primary endpoint showing a significant reduction in clinical decline at the highest dose of aducanumab, and while ENGAGE was still considered a failure in the new analysis, Biogen said it believes results from a subset of patients in that trial "who received sufficient exposure to high-dose aducanumab support the findings from EMERGE."
Specifically, aducanumab-treated patients achieved significant improvements on measures of cognition and function, such as memory, orientation and language, and also saw benefits on various activities of daily living. According to the companies, the new 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 measured by the Clinical Dementia Rating-Sum of Boxes (CDR-SB) scale.
Still, Mizuho analyst Salim Syed was cautious, saying that while the aducanumab news "sounds" positive, FDA approval is not guaranteed. He said Biogen was "pretty explicit" that EMERGE and ENGAGE are identically designed studies, "so the question here is why would two identically designed studies have disparate results." However, the jump in Biogen's share value on Tuesday suggests investors see a 50% chance of the drug being approved, according to SVB Leerink's Geoffrey Porges. He pegs the odds of approval even higher, at two-thirds, based on the company's remarks about its talks with the FDA.
Biogen and Eisai noted that the US filing will include the complete set of data from the Phase III trials, as well as results from Phase I/Ib studies. If approved, aducanumab would become the first therapy to reduce the clinical decline of Alzheimer's disease and also the first to show better clinical outcomes with the removal of amyloid beta, the companies added. The companies also indicated that they will continue discussions on a potential aducanumab filing with regulatory authorities in international markets, including Europe and Japan.
The failure of aducanumab earlier this year added to the list of experimental Alzheimer's disease drugs, particularly those targeting amyloid beta, that had been discarded due to lack of efficacy. In January, Roche halted two Phase III trials of the anti-beta-amyloid molecule crenezumab in patients with early sporadic Alzheimer's disease after a pre-planned interim analysis indicated that the studies were unlikely to meet their primary endpoints.
For further analysis, see ViewPoints: Biogen's aducanumab about-face – stunning resurrection or Hail Mary?. Also read, KOL Views: Reassessing Biogen's aducanumab in light of DMC's immaculate misconception.
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