The US Food and Drug Administration on Monday approved the drug for antibodies Aduhelm (generic name aducanumab) for the treatment of Alzheimer’s disease. Aduhelm is the first new drug for Alzheimer’s disease to receive FDA approval since 2003. It is also the first drug to address the theoretical cause of irreversible neurodegenerative disease ̵
The approval is without a doubt a landmark. This can give hope to millions of patients who currently have few options. And given these limited capabilities, it will certainly provide a huge money maker for its developer, Biogen, which has already set the list price for Aduhelm’s annual value at $ 56,000. Analysts estimate that the drug will bring sales of 5 to 6 billion dollars a year in the United States alone.
But FDA approval is far from a celebrated decision, and the drug is far from an obvious success. Following FDA approval yesterday, researchers and pharmacy observers called the agency’s decision “disgraceful,” a “serious mistake,” and a “dangerous precedent” that would ultimately “undermine the agency’s credibility as a whole.”
Critics of the decision note that Aduhelm has little evidence to show that it is effective in treating Alzheimer’s disease and comes with a serious risk of painful brain swelling. In fact, Aduhelm initially dropped two randomized, double-blind, placebo-controlled phase III clinical trials in 2019. An early analysis called the drug “useless,” and Biogen ended the trials earlier.
But later that year, Biogen shockingly resurrected the drug, saying residual data from one study showed modest, statistically significant benefits. According to Biogen, later analyzes showed that people who received a high dose of the drug (which was the FDA-approved dose on Monday) noticed a slight reduction in beta-amyloid plaques in 78 weeks. And participants in one of the experiments saw a slight improvement in the cognitive test. However, the participants in the other process still saw no benefit. Meanwhile, about 40% of people who receive the approved dose develop brain swelling.
And with that, Biogen sent the data to the FDA for review – which turned out to be bad.
A statistical evaluation by FDA reviewers (p. 247) completely dismantled Biogen’s analysis, concluding that “there is no convincing substantial evidence of a curative effect or delay in the disease” and “another study is needed to confirm or deny the positive and negative study “.
Similarly, in November 2020, an independent FDA advisory committee flatly rejected the drug and Biogen data. Ten of the 11 members of the commission voted “no” to the question of whether it was “reasonable” to consider the limited data collected from the nutrient as “primary evidence of the effectiveness of visvanumab in treating Alzheimer’s disease”. Article 11 votes “uncertainly”.
One of the non-voting members of the commission later noted the “inconsistency” of Biogen’s pink intake with the drug and the actual data behind it. “It just seems to me that the audio and video on television are out of sync and there are literally a dozen red threads that suggest concerns about the consistency of the evidence – a dozen,” said Caleb Alexander, a professor of epidemiology and medicine at John’s School of Public Health. Hopkins Bloomberg said at the meeting. “For every point you can find offering support, there are one or two more points to worry about.”
However, the FDA approved the drug on Monday based on the same data. The agency justified the decision by saying that it did not approve Aduhelm on the basis of efficacy, but rather a “surrogate endpoint”, which in this case is the drug’s potential to clear beta-amyloid lumps – this may or may not be the main reason for the disease.
In a publication explaining the agency’s decision, Patricia Cavazzoni, director of the FDA’s Center for Drug Evaluation and Research, wrote:
Ultimately, we decided to use the accelerated approval pathway, a pathway designed to provide earlier access to potentially valuable therapies for patients with serious illnesses who have an unmet need and where there are expectations of clinical benefit despite some residual uncertainty about this. advantage … [T]re-treatment with Aduhelm was clearly shown in all studies for a significant reduction in amyloid beta plaques. This reduction in plaque is likely to lead to clinical benefit. After the Advisory Committee provided its feedback, the review and discussions continued and we decided that the evidence presented in the Aduhelm application met the standard for accelerated approval.
The decision stunned and shocked outside researchers.
“This sets a dangerous precedent for future drugs in the fight against Alzheimer’s and other complex diseases,” Mark Dallas, a neurologist at the University of Reading, said in a statement. “In many ways, the clinical trials undertaken do not give a clear picture that this drug will have tangible benefits for people living with dementia.”
Robert Howard, a professor of psychiatry at University College London, echoed the theme, saying: “As a dementia clinician and researcher with personal family experience of Alzheimer’s, I want to see effective treatment for dementia like anyone else. I believe that the approval of isvanumab is a serious mistake that will only have a negative impact on patients and their families and that could undermine the current search for meaningful dementia treatments for a decade. “
Meanwhile, pharmaceutical industry observers are worried that FDA approval will set a disturbing precedent in which the need for effective treatment outweighs the need to determine if a drug is actually effective.
A well-known veteran of the pharmaceutical industry and blogger, Derek Lowe did not hold back, calling the FDA’s decision “disgraceful.” He envisioned a scenario in which other drug manufacturers seeking approval would have little efficacy data, leading to a market for approved drugs that have a record of efficacy similar to the food additive industry.
“I think this is one of the worst FDA decisions I’ve ever seen, because – like the advisory committee that looked at the application and like the FDA’s own statisticians – I don’t believe Biogen is really effective.” Lowe writes.