Today's approval goes against the advice of an outside advisory committee.
After much controversy and back and forth. FDA finally approved aducanumab (Aduhelm,
Biogen) for patients with Alzheimer’s disease.
In November 2020, FDA advisory committee of outside experts voted against recommending approval of Aduhelm, the first novel therapy approved for Alzheimer’s since 2003. Plus, clinical trial results for the drug have been mixed. At one point, Biogen shelved the drug before re-analyzing trial results and restarting the process for gaining FDA clearance.
The new drug is expected to generate billions of dollars in revenue for Biogen, CNBC reported. The Institute for Clinical and Economic Review (ICER)., a not-for-profit organization in Boston that issues reports on drug pricing and value, said in a draft report issued in May that the drug, based on the results of two critical clinical trials, should be $2,500 to $8,300 for a year's worth of treatment. A more optimistic appraisal of the drug's efficacy yielded a price range of $11,100 to $23,100 annually, according to ICER's cost-effectiveness math.
Dr. Patrizia Cavazzoni, director of FDA’s Center for Drug Evaluation and Research, acknowledged the controversy and questions surrounding Aduhelm. “There has been considerable public debate on whether Aduhelm should be approved,” she said in a statement. “The data included in the applicant’s submission were highly complex and left residual uncertainties regarding clinical benefit.”
At the same time, Aduhelm’s approval is significant since it is the first treatment directed at the underlying pathophysiology of Alzheimer’s disease, the presence of amyloid beta plaques in the brain, Cavazzoni said.
“The clinical trials for Aduhelm were the first to show that a reduction in these plaques—a hallmark finding in the brain of patients with Alzheimer’s—is expected to lead to a reduction in the clinical decline of this devastating form of dementia,” she said.
“This approval allows people living with Alzheimer’s more time to live better,” Harry Johns, CEO of the Alzheimer’s Association, said in a statement. For families it means being able to hold on to their loved ones longer. It is about reinvigorating scientists and companies in the fight against this scourge of a disease. It is about hope.”
FDA followed its usual course of action “when making regulatory decisions in situations where the data are not straightforward,” Cavazzoni said. “We examined the clinical trial findings with a fine-tooth comb, we solicited input from the Peripheral and Central Nervous System Drugs Advisory Committee, we listened to the perspectives of the patient community, and we reviewed all relevant data.”
FDA ultimately decided to use the Accelerated Approval pathway, which is intended to provide earlier access to potentially valuable therapies for patients with serious diseases where there is an unmet need, and where there is an expectation of clinical benefit despite some residual uncertainty regarding that benefit, Cavazzoni explained.
“In determining that the application met the requirements for Accelerated Approval, the Agency concluded that the benefits of Aduhelm for patients with Alzheimer’s disease outweighed the risks of the therapy,” she added.
The late-stage development program for Aduhelm consisted of two phase 3 clinical trials. One study met the primary endpoint, showing reduction in clinical decline, while the second trial did not meet the primary endpoint.
However, in all studies in which it was evaluated, Aduhelm consistently and very convincingly reduced the level of amyloid plaques in the brain in a dose- and time-dependent fashion. “It is expected that the reduction in amyloid plaque will result in a reduction in clinical decline,” Cavazzoni said.
FDA will continue to monitor Aduhelm as it reaches the market and the agency is requiring Biogen to conduct a post-approval clinical trial to verify the drug’s clinical benefit. “If the drug does not work as intended, we can take steps to remove it from the market. But hopefully, we will see further evidence of benefit in the clinical trial and as greater numbers of people receive Aduhelm,” Cavazzoni said.