Biogen has completed the submission of a Biologics License Application (BLA) of its monoclonal antibody (mAb) aducanumab to the FDA for the treatment of Alzheimer’s disease (AD). Experts in the field agreed that the drug actually works to clear amyloid plaques in the brain; however, they expressed doubts about its approval from federal regulators, even though the FDA could decide to approve the treatment due to the significant unmet needs in this disease area where no drug has been approved in the past 17 years.
Aducanumab is a recombinant human mAb that binds primarily to aggregated forms of Aβ, including soluble oligomers and insoluble fibrils, but reportedly does not bind Aβ monomers. The potential approval for aducanumab is not likely to be the final treatment for AD, but it could open doors for combination research, namely anti-Aβ therapies with anti-tau-therapies. Combination therapy is likely the way to go for the Aβ inhibitor treatment class, but combination research cannot be explored until a drug is approved. The approval could also encourage companies with other amyloid-based therapies that failed before to continue testing and attract investors to raise money for the research.
Aducanumab is expected to be the first drug to reach the AD market; however, Biogen has raised scepticism and criticism about how the data from ENGAGE and EMERGE were analyzed and for the decision to seek FDA approval of the drug after trials were halted in May 2019.
The data from the EMERGE study were positive with convincing clinical efficacy with the high-dose arm; however, the ENGAGE study did not show the same pattern of target engagement or clinical efficacy. Key opinion leaders (KOLs) interviewed by GlobalData expressed mixed opinions about the potential FDA approval, as its standard of approval is substantial evidence of efficacy and the cumulative data for aducanumab are not really exhaustive enough to meet this standard. However, they are unlikely to turn down aducanumab even if its benefit is modest, given the lack of any therapy that is truly efficacious.
In March 2020, Biogen started a new Phase IIIb open-label, multicenter safety study of aducanumab named EMBARK, enrolling subjects with AD who had previously participated in the aducanumab studies to evaluate the long-term safety and tolerability of aducanumab after a wash-out period imposed by the discontinuation of feeder studies in participants who had previously received aducanumab or who had previously received placebo. The trial was expected to be completed in Q3 2023; however, the trial has been halted due to the Covid-19 pandemic, so it may take more time to complete the trial.
KOLs interviewed by GlobalData were consistently enthusiastic about aducanumab’s potential and identified it as the most promising drug in the AD pipeline, but its route of administration—intravenous infusion—could be an issue if infusion centres are not available. Concerns regarding patients developing amyloid-related imaging abnormalities (ARIAs) can represent another barrier to the uptake for aducanumab. Physicians also will be obliged to do regular MRIs on patients to see if they have ARIA reactions, which could be a limitation, as repeated MRIs represent an additional economic burden.