Experts fear FDA push to get neurological drugs to market faster shortchanges patients

Katherine Ellen Foley, Politico Pro, October 20, 2023

The push to bring new treatments sooner to patients with devastating neurological illnesses may be giving them false hope instead.

The FDA has approved nine treatments for such conditions since 2016 under a process known as accelerated approval — intended to fill an unmet medical need. The drugs are endorsed with the understanding that they are not guaranteed to treat the disease but are rather backed by data regulators and drugmakers believe could predict the treatment’s success once it’s cleared for patient use.

But some experts fear the FDA has loosened its standards too much when approving drugs for some neurological diseases through this process amid pressure from some lawmakers and desperate patients. Even though the agency has brought pharmaceutical options to patients who have none, it’s not clear that the drugs, which are usually very expensive, end up helping or leading to better treatments later.

“In the pursuit of life-saving drugs, benefiting people with a huge unmet medical need, we are sacrificing our standards of evidence and then we don’t know if the drugs actually work or not,” said Dr. Edward Cliff, an oncology fellow and research fellow at Harvard Medical School. “It’s like this slippery slope.” And the data used to assess a drug’s potential benefit is far less definitive than for other types of conditions, such as HIV and cancer.


Accelerated approval grew significantly in response to advocates pushing the FDA to speed up getting drugs to people dying from AIDS. In 1992, the agency finalized the regulatory pathway that relied on alternative metrics beyond the conventional clinical trials that would indicate the drug would likely help patients. Treatments approved this way still have to prove they benefit patients based on the results of clinical trials. The agency can withdraw a drug from the market if the trials don’t pan out, but patients would have a drug to take in the meantime.


“You don’t have to have a PhD in biostatistics to understand that just because ‘A’ and ‘B’ co-occur, it doesn’t mean A causes B,” said Dr. Caleb Alexander, a professor of epidemiology at Johns Hopkins Bloomberg School of Public Health. “The FDA has been incredibly generous in their interpretation of fairly ambiguous scientific evidence as they approve products in this pathway.”

Diana Zuckerman, president of the National Center for Health Research, points to the accelerated approval of a drug for Duchenne muscular dystrophy, a rare, fatal neuromuscular disease that afflicts young boys.

The FDA granted Exondys 51 accelerated approval in 2016 with substantial lawmaker support, against the recommendations of the agency’s review staff and expert advisers. Sarepta, the drug’s manufacturer, provided the agency with data from 12 patients who received Exondys 51. It showed small changes in some of the metrics the agency decided would lead to patient benefit, but staff scientists were concerned that the changes were not enough and the sample size too small to ally safety concerns.

“I’ve worked on FDA issues for many years, and I’ve never seen anything like this,” said Zuckerman, who wrote a paper on the fallout from Exondys 51’s approval. She fears that some companies are taking advantage of the FDA’s regulatory flexibility with regard to rare diseases, leading to approvals based on not enough data.

Confirmatory trials for many of the drugs granted accelerated approval are ongoing and often take far longer than anticipated. An HHS inspector general report from 2022 found that roughly a third of drugs that received accelerated approval had at least one trial go beyond its expected end date — meaning expensive drugs with little to no benefits could stay on the market for years.


Many patients take to the FDA’s public advisory committee meetings, which provide an opportunity for external experts to weigh the merits of a company’s accelerated approval application. During public comment periods of those meetings, patients and their caregivers deliver heartfelt comments or speak about how their own conditions had improved with the treatment, having participated in the clinical trial.

The problem, Zuckerman said, is that the tradeoff ends up stifling drug development because companies lean on metrics that have been relied on previously to bring products to the market.

“When a company learns they can get away with something, they’re going to keep getting away with it,” she said. “Once [the FDA] has said ‘yes’ to one drug, the chances of them continuing to say ‘yes’ gets more and more likely.”


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