Could an Alzheimer’s drug finally be on the horizon? Possibly ― if the FDA agrees with data from several Biogen clinical trials ― but approval is still far from a sure bet.
The company, on July 9, submitted its biologics license application (BLA) for aducanumab, an investigational treatment for the disease. The submission includes clinical data from Phase 3 EMERGE and ENGAGE studies, as well as the Phase 1B PRIME study. Biogen has requested an accelerated review, potentially putting the medication on a path for a final decision by March 2021. However, data from these Phase 3 trials are not without controversy in the scientific community.
“Aducanumab, a so-called monoclonal antibody designed to target amyloid plaque in the brain, has been one of the most closely watched drugs in development for several years,” according to Bloomberg News.
In March 2019, Biogen and Japanese partner Eisai announced they were stopping the trials because they were not likely to meet their primary endpoints. However, in a surprise announcement in October, they reversed themselves and relaunched the studies based on the analysis of additional data. The move created widespread skepticism among scientists and researchers while reigniting the hopes of families who deal with this devastating neurodegenerative disease.
Scientists late last year expressed “cautious optimism” in a Washington Post story about what could be the first breakthrough in treating Alzheimer’s disease in nearly two decades. Time’s website has a good recap of the controversy surrounding the clinical trials and Biogen’s subsequent decision to reverse course, leading to last week’s submission.
“Aducanumab would be the first new therapy for Alzheimer’s disease in over a decade, and I look forward to the FDA review,” Judith Heidebrink, M.D., a neurology professor at Michigan Medicine who researches and cares for dementia patients, said in an email. “Unfortunately, the pivotal trials of aducanumab were stopped early, making it difficult to interpret the remaining data.”
The trials were multi-center, randomized, double-blind, placebo-controlled, parallel-group studies designed to evaluate the efficacy and safety of aducanumab, compared with a placebo, in reducing cognitive and functional impairment. In a re-analysis of EMERGE trial data, researchers found that patients who received high doses of aducanumab experienced a slowing of decline on measures of cognition and function such as memory, orientation and language after 78 weeks. Patients also experienced a slowing of decline in activities of daily living, such as managing their finances, performing basic household chores and traveling independently outside the home.
Meanwhile, the second Phase 3 trial, ENGAGE, still failed to meet its primary endpoint. However, Biogen said additional analysis did find that a subset of patients who received high doses of the drug supported the later results of the EMERGE study.
“The highest dose does appear to slow progression in persons with early symptoms of Alzheimer’s disease. The biomarker data is also encouraging, though the overall risk/benefit ratio will need careful review,” said Heidebrink, who also is the University of Michigan site principal investigator and steering committee member for the Alzheimer’s Disease Cooperative Study and leads the University of Michigan’s participation in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).
The Phase 1B PRIME study, using patients with early Alzheimer’s disease, indicated that Aducanumab reduced amyloid-beta plaque in a dose- and time-dependent fashion. Analyses of exploratory clinical endpoints showed a reduction of clinical decline, which continued for up to 48 months, according to Biogen.
“Alzheimer’s disease remains one of the greatest public health challenges of our time. It robs memories, independence and eventually the ability to perform basic tasks from the people we love,” said Michel Vounatsos, Biogen’s chief executive officer, in a statement. “The aducanumab BLA is the first filing for FDA approval of a treatment that addresses the clinical decline associated with this devastating condition, as well as the pathology of the disease. We are committed to driving progress for the Alzheimer’s disease community and look forward to the FDA’s review of our filing.”
It’s now up to the FDA to decide whether to green-light the drug. We should know in about 60 days.