The FDA’s approval of Biogen’s treatment for Alzheimer’s disease has raised questions about the agency’s expedited approval process.
The FDA’s surprise decision this week to approve Biogen’s treatment for Alzheimer’s disease has raised serious questions about the validity and value of the agency’s expedited approval process. The agency approved Aduhelm (aducanumab) based on data from a clinical trial that shows some effect on reducing beta-amyloid plaques in patients with mild cognitive impairment. Unlike most surrogate markers supporting early approval, this effect has not been linked to clinical benefit, which calls into question its validity in anticipating patient gains.
Additionally, the broad labeling approved for the new drug has sparked heated debate among scientists, researchers, patients and payers about the long-term impact of the approval decision on the credibility and independence of FDA decisions. Following an evaluation of several cancer therapies that have achieved accelerated approval but failed to document long-term benefits, the decision raised questions about the approval of new drugs and biologics based on evidence. preliminary to a possible benefit awaiting further confirmation. The FDA’s Emergency Use Clearances (EUA) for some questionable and harmful anti-COVID-19 treatments have already eroded public confidence in the scientific and medical validity of some of the agency’s actions, and many officials Researchers fear that this recent decision may exacerbate these concerns.
The very high price set by Biogen for the treatment also intensifies the debate over pharmaceutical costs, reimbursement and prescribing. By setting a price of $ 56,000 per year, well above the breakeven point of $ 2,500 to $ 8,000 calculated by the Institute for Clinical and Economic Review (ICER), Biogen is expected to earn some $ 17 billion per year. thanks to the drug, according to Wall Street. analysts, especially with a label that opens the prescription to patients with early and severe Alzheimer’s disease. All eyes are on how Medicare and the health and drug plans will define the parameters of coverage and how doctors and medical authorities will identify the most suitable people for treatment. The ICER will further examine the appropriate use of the drug and insurance coverage at a meeting on July 15, 2021. Biogen says it has started negotiating value-based contracts with major payers such as Cigna and CVS. Health to support access to medicine. But it remains to be seen how the parties will tie the payment to the outcome of the treatment.
Undermine early approvals
The FDA’s fast-track approval process was initiated in the 1980s to provide timely access to treatment to patients dying of AIDS with no treatment available. Since then, it has been used to speed up the approval of new therapies, primarily for AIDS and cancer, where validated surrogate markers have provided evidence that a drug has the potential to curb disease. Many accelerated approval products have been able to document the continued benefits of post-approval studies, building support from industry sponsors and patient advocates for the process. Some consumer groups and healthcare providers, however, complain of long delays in confirming benefits and questioned the often high cost of paying for unproven treatments.
In April 2021, the FDA held an unusual three-day meeting of its Oncology Drug Advisory Committee to assess additional indications for several leading cancer therapies, where confirmatory trials provided only limited evidence of continued clinical benefit. Although the FDA has revoked the added indication for a single product, it continues to review these therapies and fight the challenges of conducting post-approval trials. Biogen is not expected to provide confirmatory data from a post-approval study for years, if not decades, further undermining the fast-track approval paradigm.
It remains to be seen whether the flexibility applied by FDA reviewers to the new Alzheimer’s disease drug reflects a broader and less rigorous approach to approving treatments for devastating conditions requiring urgent treatment. The importance of the FDA’s action is evident in a personal message from Patrizia Cavazzoni, director of the Center for Drug Evaluation and Research (CDER). She notes that CDER reviewers carefully examined very complex data to come to the conclusion that the surrogate endpoint is “reasonably likely” to predict clinical benefit. Cavazzoni acknowledges the “residual uncertainties” about the drug and its potential to reduce clinical decline in Alzheimer’s disease, but critics maintain that this study and previous ones show no link between the reduction of amyloids in the brain and the improved health. By basing its approval on “potential benefit,” as opposed to clear clinical benefit, the FDA has caused anger and confusion between its critics and its supporters.
Some industry analysts predict that this more flexible approval standard will lead to increased R&D for other Alzheimer’s disease drugs as well as other experimental treatments for rare and fatal diseases. Several leading pharmaceutical companies are testing new treatments for Alzheimer’s disease that also aim to reduce amyloid in the brain or eliminate other invasive substances. But many scientists fear that approvals based on limited evidence of clinical benefit could generate confusion and uncertainty that only deters investment in R&D.
One result, however, is that analysts and FDA experts will no longer assume that the agency’s reviewers will follow the recommendations of its advisory committees, as is generally the case. The advisory committee that evaluated the drug Biogen last November voted almost unanimously against approval based on the limited evidence of its effectiveness, but the FDA came to its own conclusion.