Aduhelm has been labelled as the first drug of its kind to target the underlying cause of Alzheimer’s disease. Its approval however has not been based on the drug’s ability to improve memory or slow down cognitive decline, but rather to reduce a build up of plaque in the brain which possibly results in Alzheimer’s progression.
Aduhelm was approved using the FDA accelerated approval pathway, which uses surrogate endpoints to save time in the drug approval process. A surrogate endpoint can be a marker than indicates a clinical benefit but is not a definite measure of it. In Adulhem’s case, the FDA approved the drug based on data that showed patients who received the treatment displayed a reduction of amyloid- beta plaque in the brain. However, Biogen will now have to assure the FDA of Adulhelm’s clinical benefit through further clinical trials.
“Alzheimer’s disease is a devastating illness that can have a profound impact on the lives of people diagnosed with the disease as well as their loved ones,” said Patrizia Cavazzoni, M.D., director of the FDA’s Center for Drug Evaluation and Research. “Currently available therapies only treat symptoms of the disease; this treatment option is the first therapy to target and affect the underlying disease process of Alzheimer’s. As we have learned from the fight against cancer, the accelerated approval pathway can bring therapies to patients faster while spurring more research and innovation.”
As Alzheimer’s disease progresses, it’s thought to bring with it changes in the brain, which include the build-up of amyloid plaques and neurofibrillary, or tau tangles, which damage neurons and their connections.
However, the hypothesis that clearing amyloid beta plaques can reduce cognitive decline hasn’t been confirmed, and some experts are sceptical about the clinical benefits of Aduhelm. According to Stat News, last November, the majority of an expert advisory committee for nervous system therapies to the FDA agreed that there was not enough evidence for Aduhlem to show that it could slow cognitive decline through the removal of amyloid beta plaque.
The efficacy of Aduhelm was evaluated in two Phase 3 clinical trials, as well a Phase 1b study, representing a total of 3,482 patients. Patients receiving the treatment displayed a reduction of amyloid beta plaque when compared to the control arm of the studies. Patients were those that had early stages of Alzheimer’s disease and a confirmed presence of amyloid pathology.
During the clinical trials, 41% of patients displayed Amyloid Related Imaging Abnormalities (ARIA) which can include headaches, confusion, dizziness, nausea. A smaller percentage of patients also showed small bleeds in the brain.
In 2019 the Phase 3 trials of Aduhlem (ENGAGE & EMERGE) were discontinued due to the fact that they were unlikely to meet their primary endpoints. Later that year Biogen shocked the industry by submitting the drug for approval. Biogen said that additional show that Aduhlem is ‘pharmacologically and clinically active’ and can reduce the clinical decline of Alzheimer’s disease.
“This historic moment is the culmination of more than a decade of groundbreaking research in the complex field of Alzheimer’s disease. We believe this first-in-class medicine will transform the treatment of people living with Alzheimer’s disease and spark continuous innovation in the years to come,” said Michel Vounatsos, chief executive officer at Biogen. “We are grateful for the contributions of thousands of patients and caregivers who participated in our clinical trials, as well as for the dedication of our scientists and researchers. Together with the healthcare community, we are ready to bring this new medicine to patients and begin to address this growing global health crisis.”
In the US, yearly treatment for the drug will cost $56,000 and depending on patients’ insurance coverage, out of pocket costs could vary.
“This is the first FDA-approved therapy that actually targets what many scientists consider to be a primary causal factor in Alzheimer’s disease pathogenesis: abnormal accumulation of the protein beta-amyloid. If beta-amyloid levels can be reduced early in the disease course, it is believed that downstream events including cognitive decline can be mitigated.
“Although aducanumab and related interventions have been shown to reduce beta-amyloid, robust cognitive benefits are less certain, which has resulted in some controversy regarding the true efficacy of the drug. The hope is that initiation of aducanumab treatment very early in the disease course will prove beneficial,” says Christian Pike, professor at the USC Leonard Davis School of Gerontology.