What are the drug approvals of A.L.S. and Alzheimer’s?

FDA’s accelerating authority isn’t going to let anybody know what’s wrong with their product or how they’re going to use it

I can understand the argument, on an emotional level, that when it comes to your body and life, you should be able to assume whatever risk you want. There’s also the compelling argument that in certain situations, whether it’s a pandemic affecting millions or a rare, devastating disease, there should be a lower bar for evidence and a greater willingness to allow people to assume risk. The Covid-19 vaccine had strong early evidence that they worked well and were safe in the F.D.A. emergency use authorization, which indicated the idea that absolute certainty about a product’s safety or efficacy is not always needed. Relief in a crisis can be provided with regulatory flexibility.

Once a drug receives accelerated approval from the F.D.A., the manufacturer is supposed to continue to collect data about its safety and effectiveness. If the confirmatory data is not convincing, the product may lose its approval. But this isn’t always happening. A report by the Inspector General in the Department of Health and Human Services found that more than a third of drug applications have incomplete confirmatory trials.

Even if the data shows a product is not safe or effective, the F.D.A. can’t quickly remove it from the market. For example, the preterm birth prevention drug Makena received accelerated approval in 2011. In October 2020, the F.D.A. proposed that it be withdrawn because the follow-up study failed to verify it worked. The drug is sold in the U.S., and the agency is going to discuss it soon.

Adding this kind of rigor will make it possible for clinicians, patients, and insurers to have more confidence in the system and the treatments it approves.

The COVID-19 vaccines weren’t granted this kind of approval. But the FDA has given accelerated approvals to more than 100 drugs aimed at treating cancer, HIV, preterm birth and other conditions over the last three decades.

In addition, the law creates new transparency requirements and a council to get everyone at the FDA on the same page about how this kind of approval should be used.

“This strengthens their hand and makes them better,” says Robin Feldman, a professor at the University of California College of the Law. “However, just because the FDA has the power doesn’t mean it’s going to use it.”

Criticism of the program crescendoed following the controversial accelerated approval of Alzheimer’s drug Aduhelm in 2021. Aduhelm’s manufacturer initially set a price of $56,000 a year — even though the FDA approved it based on its ability to remove sticky amyloid plaques from the brain without proof that plaque removal could slow patients’ loss of mental abilities. The drug flopped, with insurers refusing to cover it, and the drugmaker, Biogen, had to lower its price.

The FDA approval of Aduhelm caused a professor of medicine at a hospital to resign from an advisory committee.

His research has found flaws in the accelerated approvals program, including the fact that only 1 in 5 cancer drugs that were granted accelerated approval “demonstrated improvements in overall patient survival.”

More drugs were granted accelerated approval than traditional approval in order to increase the price of drugs.

In September, the Office of Inspector General for the Department of Health and Human Services issued a report about delinquent confirmatory studies for drugs granted accelerated approval. The report’s findings were consistent with NPR’s.

However, according to former FDA principal deputy commissioner of food and drugs Dr. Rachel Sherman, the agency has always had the power to require that confirmatory studies be underway at the time of approval, but didn’t often exercise it.

“If you have the data and there is an unmet medical need, we need to move forward”, she said at the time.

She has worked with the agency for three decades and never lost an argument. “Sometimes they convinced me they were right and I was wrong. But if I wanted something, I got it. At the end of the day, the FDA does have a bully pulpit and what’s the right word?

According to Feldman, there have been times when the FDA neglected to use their powers even though they had the power to do so.

The agency was sued by drugmakers and lost. The makers of the drug Bendeka were not given rare disease drug perks when it tried not to. The FDA was sued by the drug’s manufacturer.

Changes were expected to get folded into renewal of the Prescription Drug User Fee Act in September, but Congress passed it without any riders. That worried Dr. Reshma Ramachandran, of Yale School of Medicine, who was one of the doctors who traveled to Washington, D.C., to talk to legislators about accelerated approval updates.

We wanted to make sure they were going to stick to their commitment to revisit those reforms as part of the end-of-year spending package, she said.

The FDA tried to withdraw a failed drug, not just a confirmatory trial, but multiple other studies. “I think that really gave cause to members of Congress, but also the FDA, to really say, ‘Hey, we need to have these common sense reforms.’ “

“We wanted that to be codified in legislation so that that wouldn’t be an exception. That would just be the rule,” says Ramachandran. “When that happens, that prevents significant delays for starting the trials, but also completing the trials.”

“These are not mandatory, they are discretionary rather than compulsory,” says University of California’s Feldman. “In other words, it allows the FDA to do things, but doesn’t require the FDA to do things. So that’s a big difference.”