Biogen to Submit BLA for Aducanumab in Early 2020 Following Positive Reanalysis of Phase III Data

On October 22, Biogen and Eisai announced that, following consultations with the U.S. Food and Drug Administration (FDA), Biogen plans to submit a Biologics License Application (BLA) for the Alzheimer’s disease drug aducanumab to the FDA in early 2020, and will continue to engage in discussions with regulatory authorities in Europe, Japan, and other regions.

Affected by this news, Biogen's stock rose nearly 40% in pre-market trading.

Aducanumab (BIIB037) is an investigational monoclonal antibody that has been studied for the treatment of early-onset Alzheimer’s disease. Under a collaboration and license agreement, Biogen licensed aducanumab from Neurimmune. Since October 2017, Biogen and Eisai have collaborated globally on the development and commercialization of aducanumab.

On March 21 of this year, Biogen/Eisai announced the termination of two global Phase III trials of the Alzheimer’s drug aducanumab, codenamed ENGAGE and EMERGE, based on data analysis provided by an Independent Data Monitoring Committee. The EMERGE study enrolled 1,638 patients, while the ENGAGE study enrolled 1,647 patients. At the time of the decision to terminate in March, the primary analysis was conducted on available data up to December 26, 2018, covering a total of 1,748 patients who had the opportunity to complete the 18-month study period. It was predicted that neither trial would achieve its primary endpoint upon completion.

It is reported that Biogen’s decision to seek marketing approval was based on a new analysis conducted with the FDA, which involved a larger dataset from the Phase III clinical trials. The dataset included 3,285 patients, of whom 2,066 had the opportunity to complete the full 18-month treatment regimen. If approved, aducanumab would become the first therapy to reduce clinical decline in Alzheimer’s disease, as well as the first therapy to demonstrate that removal of amyloid-beta (Aβ) protein leads to improved clinical outcomes.

“Given that Alzheimer’s disease affects tens of millions of patients worldwide, today’s announcement is truly encouraging. It is the result of breakthrough research and demonstrates Biogen’s unwavering commitment to following the science and doing what is right for patients,” said Michel Vounatsos, Chief Executive Officer of Biogen. “We hope to provide patients with the prospect of the first therapy to slow Alzheimer’s disease, as well as to highlight the potential implications of these results for similar approaches targeting Aβ.”

The BLA submission will include data from the Phase I/Ib studies as well as complete data from the Phase III studies. The company aims to provide eligible patients who previously participated in the Phase III studies, the long-term extension study of the Phase Ib PRIME study, and the EVOLVE safety study with access to aducanumab.

Following discussions with the FDA and a review of the data, Biogen concluded that the discrepancy between the results of the new analysis of the larger dataset and the predictions from the futility analysis was primarily attributable to greater patient exposure to high-dose aducanumab. In the new analysis of the larger dataset, multiple factors contributed to this increased exposure to aducanumab, including data from a larger number of patients, a longer mean duration of exposure to the high dose, the timing of protocol amendments that allowed a greater proportion of patients to receive the high dose, as well as the timing of the futility analysis and its prespecified criteria.

Source: PharmaCube Plus