3 CDER Officials Defend Aduhelm Approval
The three senior CDER officials involved in the controversial approval of Biogen’s Aduhelm (aducanumab) to treat Alzheimer’s disease are defending their action as consistent with FDA accelerated approval requirements and the need of Alzheimer’s patients for new treatment options. Writing in a JAMA Internal Medicine Viewpoint column, CDER director Patrizia Cavazzoni, Office of Neuroscience director Billy Dunn, and Office of New Drugs director Peter Stein say although evidence from the aducanumab development program suggested a clinical benefit (strongly in one of three studies with support from a second study) they concluded, as did the members of the agency’s Peripheral and Central Nervous System Advisory Committee, that the clinical trial data were not adequate on their own to convincingly demonstrate a clinical benefit in reducing clinical decline in patients with Alzheimer’s disease.
“After reaching this conclusion, we faced a challenge: available evidence was strongly suggestive of a benefit from aducanumab but was complicated and in some respects contradictory; yet patients with Alzheimer’s disease are in urgent need of treatments that delay disease progression and loss of function,” the three write. “Such a situation is recognized and addressed in the statute that provides FDA with the authority to approve a drug using the accelerated approval pathway.”
The article says accelerated approval is intended to provide earlier access to drugs for serious diseases when there is residual uncertainty at the time of approval regarding the drug’s ultimate clinical benefit. It says aducanumab meets the four criteria in the law for accelerated approval and Biogen is required to conduct a post-approval trial to verify benefit.
“In weighing the benefits versus the risks of aducanumab, we considered that Alzheimer disease leads to irreversible loss of memory, cognition, and ability to function in daily activities,” Cavazzoni and her colleagues write. “In listening sessions, we heard from patients and their families about the devastating toll the disease has taken and their desire for a treatment to stop or delay functional losses. Many made it clear that they are willing to accept the trade-off of some uncertainty about clinical benefit in exchange for earlier access to a potentially effective drug, which is the exact premise and intent of accelerated approval. If instead, approval had been delayed, the loss of brain function in these patients over this time, which might have been lessened by earlier initiation of treatment, would not be regained.”