Following lower-than-expected results and diminished prospects for its Alzheimer’s drug, Aduhelm (aducanumab), once touted as a potential blockbuster, Biogen announced that its CEO is stepping down, and the company is implementing a $500-million cost-reduction program, which involves substantially eliminating the commercial infrastructure for the drug. The $500-million is in addition to further cost-reductions announced by the company in December (December 2021) to bring its total annualized cost-savings to $1 billion.

Biogen incurred a major setback for the drug earlier this month (April 2022) when the US Centers for Medicaid and Medicare Services (CMS) restricted coverage under Medicare, the US federal health insurance program for individuals 65 or older, for Aduhelm and other anti-beta-amyloid drugs for treating Alzheimer’s disease. The CMS issued a national policy for coverage of Aduhelm and any future monoclonal antibodies directed against amyloid for treating Alzheimer’s disease that are approved under FDA’s accelerated approval pathway only to patients taking part in approved clinical trials, which includes post-approval confirmatory trials. In June 2021, Aduhelm was approved under FDA’s accelerated approval pathway. The accelerated approval pathway provides patients with a serious disease earlier access to drugs when there is an expectation of clinical benefit despite some uncertainty about the clinical benefit with follow-up trials required.

The FDA’s approval of Aduhelm was the first approval in almost two decades of a new treatment for Alzheimer’s disease, but its approval came with some issues. Prior to getting the accelerated approval by the FDA, an FDA advisory committee had earlier recommended not to approve the drug, citing the need for additional research. Recommendations by FDA advisory committees are non-binding, but are usually in line with final FDA decisions, although not in this particular case. Earlier this month (April 2022), Biogen withdrew its marketing authorization application (MAA) from the European Medicines Agency for Aduhelm following discussions with the EMA, which had indicated that data provided thus far would not be sufficient to support a positive opinion for marketing authorization. Biogen’s MAA had been under review by an EMA advisory committee in response to the company’s request for a re-examination of a negative opinion issued by the committee in December (December 2021).

Following US approval under the accelerated approval pathway in June 2021, the drug posted full-year 2021 sales of $3 million and had sales of $2.8 million in the first quarter of 2022. For the first quarter of 2022, Biogen took $275 million in charges from Aduhelm inventory write-offs as well as approximately $45 million in idle-capacity charges.

Aduhelm had been projected as a key revenue contributor for the company and with its lower-than-expected results thus far and diminished commercial prospects, Michel Vounatsos, who had served as the company’s CEO since 2017, is stepping down. He will continue to serve as CEO and on the company’s Board of Directors until his successor is appointed.

Although the company is reducing commercial support for Aduhelm, it will continue funding certain regulatory and R&D activities for the drug, including the continuation of a redosing study and the initiation of a Phase IV post-marketing requirement study. Biogen says that additional actions on the drug may be informed by upcoming data readouts as well as further engagement with the FDA and CMS.

Despite its setback with Aduhelm, Biogen says it will continue development of another anti-amyloid drug for treating Alzheimer’ disease, lecanemab, which it is partnered with Eisai, who was also Biogen’s partner for Aduhelm. The companies plan to complete the rolling submission for lecanemab under the accelerated approval pathway in the US in the second quarter of 2022. The Phase III readout for lecanemab is expected in the fall of 2022, and Biogen plans to seek full FDA approval by the first quarter of 2023.

Biogen says that lecanemab and two other drugs in its neuroscience pipeline are part of its R&D prioritization for 2022:  zuranolone for treating major depressive disorder (MDD) and post-partum depression (PPD) and BIIB104, a drug in Phase II development for treating cognitive impairment associated with schizophrenia. Biogen is partnered with Sage Therapeutics, a Cambridge, Massachusetts-based bio/pharmaceutical company, to advance zuranolone. The companies have initiated the rolling submission of a new drug application (NDA) to the FDA for MDD, which is expected to be completed in the second half of 2022. The readout of the Phase III study in PPD is expected in mid-2022, with an associated NDA filing anticipated in early 2023. Biogen expects the Phase II readout for BIIB104, its other key drug candidate, in mid-2022.

Source: Biogen