On 7 June, the US Food and Drug Administration (FDA) approved Biogen’s Aduhelm (aducanumab) for the treatment of Alzheimer’s disease. No new drug for this indication had been approved for the past 18 years, despite more than 400 clinical trials and billions of dollars being spent.
Aduhelm is a recombinant human monoclonal antibody (mAb) that binds primarily to aggregated forms of amyloid beta (Aβ), including soluble oligomers and insoluble fibrils, but reportedly does not bind Aβ monomers. Biogen has received scepticism and criticism for how the data from the two main Aduhelm trials, ENGAGE and EMERGE, were analysed. In March 2019, the trials were halted after a futility analysis concluded that the trials would not reach their primary endpoint, namely the slowing of cognitive decline as measured by the Clinical Dementia Rating scale (CDR-SOB). In October 2019, however, Biogen announced that it was seeking FDA marketing approval of aducanumab, as upon re-analysing data from the trials, the EMERGE trial showed significant findings and a subset from the ENGAGE trial supported these positive findings.
Aduhelm is the first therapy to target and affect the underlying disease process of Alzheimer’s disease. All currently available therapies only treat symptoms of the disease, whereas this drug works to clear amyloid plaques in the brain. The drug does, however, face a few hurdles before it can be made available for patients. Its infusion route of administration could be an issue, as infusion centres are not available in all geographic areas. In addition, concerns regarding the development of amyloid-related imaging abnormalities (ARIAs) represent a barrier for the uptake for Aduhelm.
Physicians will also be obliged to conduct regular magnetic resonance imaging (MRI) scans of patients to see if they have ARIA reactions, which could be a limitation, as repeated MRIs represent an additional economic burden. The high cost of $50,000 a year may also impact reimbursement, which in turn could limit Aduhelm’s uptake. Despite these challenges, GlobalData forecasts that Aduhelm will generate $5.5bn worldwide by 2027. To facilitate access to Aduhelm following the FDA’s approval, Biogen and Eisai have announced a range of programmes intended to support access for all qualified patients to help them and their families understand the disease, navigate the diagnostic journey, secure culturally competent care and afford treatment.
The approval of Aduhelm is not a final solution in the treatment of Alzheimer’s disease, but it could signify a new era for the treatment of the disease. Its approval may also open doors for combination research, namely anti-Aβ therapies with anti-tau therapies. Combination therapy is likely to be the best path forward for the Aβ inhibitor treatment class, but combination research could not be explored until a drug was approved. The approval could also encourage other developers of amyloid-based therapies to continue testing and enable them to attract investors to fund much-needed research.