What happened: Top officials at the Food and Drug Administration (FDA) approved a drug to treat Alzheimer’s disease by utilizing a highly irregular process that sidelined the concerns of federal scientists and science advisors.
Why it matters: Evaluating a drug for treatment of a medical condition requires a strong science-based process to show that a drug is safe and effective, and by sidelining this process, FDA officials undermined one of the most important ways that science affects the health and safety of millions of people in the United States.
In June 2021, top officials at the Food and Drug Administration (FDA) under the Biden administration approved the drug Aduhelm for treatment of Alzheimer’s disease in a nonstandard process that failed to incorporate the concerns from FDA scientists and FDA advisory committee members. FDA officials also carried out a set of nonstandard and unusually frequent meetings with the drug’s pharmaceutical manufacturer, Biogen, where observers reported a much more collaborative process than would be typical between a regulatory agency and the company under its regulatory purview.
Statisticians at the FDA, such as Sylva Collins, the Director of the FDA’s Office of Biostatistics, stated in an official memo that they were opposed to the approval of Aduhelm since there was not enough evidence to show that the drug was effective. The FDA statisticians based their recommendations on conflicting evidence from two Phase 3 clinical trials – the largest and most comprehensive clinical trials to test a treatment’s safety and effectiveness – one of which showed a positive result and the other of which showed a negative result. An FDA advisory committee of independent scientific experts, the Peripheral and Central Nervous System Drugs Advisory Committee, came to the same conclusion and almost unanimously voted to reject the drug’s approval. When FDA officials approved Aduhelm, three advisory committee members resigned in protest over the decision. Even some scientists at Biogen who worked on the early stages of the Aduhelm disagreed with the FDA’s decision to approve the drug.
The agency greenlit the drug under a program called “accelerated approval.” This is a truncated approval process that is not based on the normal method for evaluating a drug, e.g., the weight of the scientific evidence demonstrating a drug’s safety and effectiveness. Instead, the approval is based on preliminary evidence that an indirect biological marker shows that the drug would be reasonably likely to predict clinical benefit.
Use of the accelerated approval process in this circumstance breaks with years of agency precedent. Normally, the accelerated approval process is used when treatments have not undergone a Phase 3 trial. However, Aduhelm underwent two Phase 3 trials and the evidence was conflicting. According to documents released by the FDA, top FDA officials redefined how to utilize the accelerated approval process more broadly, by stating that it can be utilized “upon a determination that the product has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit.”
FDA officials stated that they used the accelerated approval process because of the drug’s ability to remove beta-amyloid brain plaques. For several years, beta-amyloid plaques were believed by researchers to contribute to the disease. However, new evidence is suggesting that beta-amyloid plaques may only have a small role or even no role in the development of Alzheimer’s disease, and that the previous research showing the connection between the beta-amyloid protein and the development of Alzheimer’s disease was based on misleading evidence. The consensus among Alzheimer’s researchers is that there is not enough evidence to suggest that reducing the beta-amyloid plaques can provide clinical benefits to Alzheimer’s patients.
By approving Aduhelm, the FDA under the Biden administration failed to adhere to one of its primary duties of protecting “public health by ensuring the safety, efficacy, and security of human and veterinary drugs, biological products, and medical devices.” The science-based concerns raised by FDA scientists and FDA scientific advisors were sidelined in exchange for a highly irregular process of drug approval that was not based on solid scientific evidence. People with Alzheimer’s disease deserve to have treatments available that the science suggests will ease the symptoms associated with this difficult condition, not a drug with little-to-no evidence of effectiveness.