The FDA Fails

On June 7, the U.S. Food and Drug Administration (FDA) over-ruled the advice of its own expert advisory panel and approved for sale Biogen’s aducanumab, a manufactured monoclonal antibody that will be marketed as Aduhelm, for the treatment of Alzheimer’s disease (AD). Since then, at least three of its experts have resigned from their advisory roles in protest. The drug, which requires monthly IV infusion, will be priced at $56,000 per year.

The stock market certainly applauded the FDA decision: Biogen’s stock price rose 38% on the day of the announcement. The Alzheimer’s Disease Association took out a full page ad in the Wall Street Journal applauding this “breakthrough” approval. The response of the medical community has been much more muted, with a majority of experts who treat dementia urging caution in its adoption.

Why the sharp difference? Amyloid, an abnormal protein made of clumps of naturally occurring proteins, is a hallmark pathologic finding in the brain of patients with AD. Whether it causes AD or is simply a marker is unclear. A variety of similar drugs have been tested over the years and while many have reduced the amount of amyloid in the brain, none have produced any clinical benefit.

Biogen sponsored two trials of aducanumab and both were stopped by their steering committees because no benefit was seen. Biogen then reanalyzed one of the trials and did show some benefit. Despite the claim of “breakthrough,” even the benefit found by Biogen’s scientists was at best modest. The difference in a score of AD severity between treated and untreated patients was 0.39, on a scale of 0 to 18 – statistically significant according to Biogen but hardly overwhelming.

Additional concerns raised by objectors were that 1% of patients receiving the active drug had major side effects, primarily due to the brain swelling that occurs early in treatment, and this was in the setting of a clinical trial, with very close patient monitoring and dose adjustments made based on brain imaging – conditions unlikely to be met in the real world. Finally, patients in these trials were very carefully selected, with mild AD and with specific findings in the brain on PET scans, scans not covered by Medicare or most health insurers.

AD is such a devastating illness, with tragic impact on both the sufferers and on their caregivers, that I fear the pressure on physicians will be overwhelming to prescribe aducanumab to every AD patient for want of any good alternatives. This is likely to harm more patients than it helps. It will also add to the already enormous cost burden faced by patients and their families, as the cost of the drug is unlikely to be paid by many commercial insurers and no insurer will pay for the associated scan costs.

The FDA’s role is to protect the public from pharmaceutical companies’ natural desire to market products on which they have spent huge amounts of development and testing money. In the case of Biogen, the FDA has failed the public.

Prescription for Bankruptcy. Buy the book on Amazon