The U.S. Food and Drug Administration (FDA) has approved the antibody drug Aduhelm (generic name aducanumab) to treat Alzheimer’s disease. Aduhelm is the first new Alzheimer’s drug to be approved. from the FDA since 2003. It is also the first drug to target the theory of irreversible neurological disease. This is a group of beta-amyloid peptides that form in the brains of Alzheimer̵7;s patients. rather than treating the symptoms of the disease
The approval was undoubtedly a landmark. It could give hope to millions of patients who today have few options. and with those limited options It will certainly provide a big money maker to the developer Biogen, which has set an annual list price for Aduhelm of $56,000. Analysts estimate the drug will bring in sales of $5 billion to $6 billion. millions of dollars per year in the United States alone.
But FDA approval is far from a famous decision. And this drug is far from a clear success. Since yesterday’s FDA approval, researchers and drug watchers have called the agency’s decision “disgraceful,” a “serious error,” and a “dangerous precedent” that would end up being “disgraceful.” “Destroys confidence in the organization as a whole”
Critics note the decision that Aduhelm has little data to indicate its effectiveness in treating Alzheimer’s disease. and are at high risk of developing painful swelling of the brain In fact, Aduhelm initially dropped out of two randomized, placebo-controlled, Phase 3 clinical trials in 2019. Early analyzes dubbed the drug. “Useless” and Biogen ends early trials.
But that same year Biogen has surprisingly resurrected the drug. He said the rest of the data from one trial showed a small and statistically significant benefit. According to Biogen Subsequent analyzes revealed that those who received high doses of the drug One trial (which was the FDA-approved dosage Monday) showed a slight decrease in beta-amyloid plaque over 78 weeks, and participants in one trial saw a slight improvement in their beta-amyloid plaque. cognition test Other trial participants Haven’t seen any benefit yet. At the same time, about 40 percent of people taking the approved drug developed brain swelling.
And as a result, Biogen has sent the data to the FDA for review, which is bad.
A statistical assessment by FDA investigators (p. 247) blasted Biogen’s analysis in detail, concluding that “there is no significant evidence of a curative or slowing effect” and that “another study is needed. to confirm or reject positive studies and negative studies.”
in the same way In November 2020, an independent FDA advisory committee thoroughly rejected Biogen’s drug and data. Ten of the 11 board members voted “no” on the question of whether it was “reasonable” to consider limited data by Biogen. which is compiled into “Preliminary evidence of the effectiveness of aducanumab in the treatment of Alzheimer’s disease,” the 11th member voted “uncertain.”
A non-voting board member later mentioned “The inconsistency” of Biogen’s rosy use with the drug and the real information behind it. “For me, I feel that the audio and video on TV don’t match. And there are dozens of red threads that indicate concerns about the consistency of evidence—dozens,” said member Caleb Alexander, professor of epidemiology. and medicine at the Johns Hopkins Bloomberg School of Public Health said at the meeting. “For every point you can find support advice. There was another point or two that caused concern.”
Still, the FDA approved the drug on Monday based on that same information. The agency justified its decision, saying it didn’t approve Aduhelm based on its efficacy, but rather as a “surrogate endpoint”, in which case the drug’s potential to eliminate beta-amyloid groups that may or may not cause disease.
In a post describing the agency’s decision, Patrizia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, wrote:
We finally decided to go the accelerated approval route. It is a path that is intended to provide earlier access to potentially valuable treatments for patients with severe disease in the presence of unmet needs. and where clinical benefits are expected. Although there is some uncertainty about the benefits… [T]Aduhelm therapy has been shown clearly in all trials to significantly reduce amyloid beta plaque. This reduction in plaque is likely to result in clinical benefit. After the advisory committee has made suggestions Our review and consideration is ongoing. And we decided that the evidence presented in Aduhelm’s application meets the standards for expedited approval.
The decision left outside researchers stunned and shocked.
“This is a dangerous example of future medicine in the fight against Alzheimer’s and other complex diseases,” University of Reading neuroscientist Mark Dallas said in a statement. “Many clinical trials do not offer a clear picture of how this drug will benefit individuals with dementia.”
Robert Howard, a professor of psychiatry at University College London, echoes this point: “As a physician and dementia researcher with personal family experience with Alzheimer’s disease, I’d like to see a dementia treatment as effective as anyone. I think the approval of aducanumab represents a serious mistake that will only have a negative impact on patients and their families. And that could potentially continue the search for meaningful dementia treatments for more than a decade.”
Pharmaceutical industry watchers worry that the FDA approval will set a troubling precedent where the need for an effective treatment outweighs the need to determine whether a drug is actually effective.
Derek Lowe, a pharmaceutical industry veteran and blogger, noted relentlessly and called the FDA decision “disgraceful.” He envisioned a situation where other drugmakers could seek approval with little efficacy data. This has led to an approved drug market that has a similar history of efficacy as the dietary supplement industry.
“I think this is one of the worst FDA decisions I’ve ever seen. Because—like an advisory committee that reviews applications. And like the FDA statistician itself—I don’t believe Biogen really shows its effectiveness,” Lowe wrote.