Biogen has completed a submission seeking FDA approval of its Eisai-partnered anti-amyloid beta drug candidate aducanumab for the treatment of Alzheimer's disease, the companies reported Wednesday. Biogen CEO Michel Vounatsos noted that the application "is the first filing for FDA approval of a treatment that addresses the clinical decline associated with this devastating condition, as well as the pathology of the disease."
Biogen, which has requested a priority review, saw its shares climb as much as 10% on the news. At a recent earnings call, the company said it was aiming for the application to be complete in the third quarter, having previously said it planned to submit the once-failed drug for US approval in early 2020 (for more, see ViewPoints: Delay fans flames of doubt about Biogen's all-important aducanumab).
Skepticism over data package
Stifel analyst Paul Matteis indicated that the filing, while mostly expected, "does represent an incremental positive after recent delays seeded additional skepticism surrounding the regulatory path." Still, he remains "skeptical on the clinical data package" for aducanumab, and considers the therapy to have only a 33% probability of success. Although Matteis conceded that if Biogen is granted a priority review, then that would suggest the FDA is leaning positively.
According to Biogen and Eisai, the completed application follows "ongoing collaboration with the FDA," and contains clinical data from the Phase III EMERGE and ENGAGE trials testing aducanumab in patients with mild cognitive impairment due to Alzheimer's disease and mild Alzheimer's disease dementia, as well as from the Phase Ib PRIME study. The companies had discontinued EMERGE and ENGAGE in March last year after a failed futility analysis. They reversed course in October and revived plans to seek US approval, claiming that positive results from a new analysis of the trials backed the effectiveness of high-dose aducanumab when administered to patients over an extended period.
Specifically, the companies said that EMERGE in fact met its primary endpoint, with patients on high-dose aducanumab showing a significant 22% reduction of clinical decline from baseline on Clinical Dementia Rating-Sum of Boxes (CDR-SB) scores at 78 weeks versus placebo. They also exhibited a "consistent reduction" of clinical decline as measured by pre-specified secondary endpoints, the companies said. Further, imaging of amyloid plaque deposition in EMERGE demonstrated that amyloid plaque burden was reduced with low- and high-dose aducanumab compared to placebo at 26 weeks and 78 weeks. Meanwhile, the new analysis still showed that ENGAGE was a failed study, although Biogen reiterated Wednesday that it believes a subset of data from this trial "are supportive of the outcome in EMERGE."
In addition to submitting the FDA filing for aducanumab, Biogen said it has continued to engage in dialogue with regulatory authorities in other markets, including Europe and Japan, with the goal of eventually submitting applications in these markets as well.
Analysts have been closely watching aducanumab as Biogen looks to shore up its growth prospects amid concerns over patents for its multiple sclerosis drug Tecfidera (dimethyl fumarate) and competition for its spinal muscular atrophy treatment Spinraza (nusinersen). Biogen recently lost a US patent dispute with Mylan over Tecfidera, the company's highest selling drug at $1.1 billion in sales during the first quarter. Mizuho Securities analyst Salim Syed said at the time that he still viewed aducanumab as a "risky proposition" for Biogen, while Piper Sandler's Christopher Raymond saw the filing and review of aducanumab more as "a lottery ticket."
For additional analysis, see ViewPoints: Tecfidera decision has investors betting it all on aducanumab, and ViewPoints: Investors see aducanumab as insulated from Eli Lilly, Roche AD failures – will regulators agree?
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