Short Wave - The Accelerated Approvals Process: Are Drugmakers Fulfilling Their Promises?

Episode Date: July 22, 2022

The Food and Drug Administration allows faster drug approvals based on preliminary study data if the drug fulfills an unmet medical need. But the speedy approval comes with a promise that the drugmaker does another clinical trial once the drug is on the market to prove it really works. If not, the FDA can rescind the approval. How are the companies doing and how well does the agency enforce that system? Pharmaceuticals correspondent Sydney Lupkin investigated the 30-year track record for accelerated approvals. Today, her findings on stalled trials and missing evidence.See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. In the summer of 2013, Michael Alkiyaga was a high school student on the basketball team and the baseball team. He had friends, a girlfriend, an Xbox. Things were pretty good. But he kept getting these nosebleeds and they were getting worse despite medical procedures to fix them. I woke up in the morning and I went to go wake him up and I went in his room and it looked like a crime scene. I mean, he had he had his short. off and he was sleeping sitting up in his bed and he had blood all over him, all over his pillow,

all over his bed. And I just woke him up and I was like, Michael. That's his mom, Christy Alkiaga, of Everett Washington. She said he didn't want to wake her, so he fell asleep like that. Eventually, Michael was diagnosed with acute lymphoblastic leukemia, or A-L-L. But he was optimistic. He went to school, baldhead and all, and was determined to be healthy enough to play baseball in the spring. He goes, wow, well, I can't wait to be able to say that I beat cancer. The cancer had other plans. Six months later, it wasn't responding well enough to multiple rounds of chemo

and an experimental treatment that they were trying. And so running out of options, doctors thought maybe they could try the experimental treatment again at a higher dose. But first, they needed to give him a different chemotherapy that Christy remembers Michael's doctors calling the big gun. I don't even think that the infusion was complete and he started puking. And he had never done that with any of the other chemos. The big gun failed. They expected him to have kind of a rough time, you know, coming back and his numbers recovering and then have a bone marrow transplant and then, you know,

spend a little bit more time in the hospital and then be cured. And instead, he walked in that hospital and, you know, he never walked out. Michael died in May of 2014 about a month after his 16th birthday. The Food and Drug Administration gave this strong chemo, clofarabine, something called accelerated approval in 2004 under the brand name Clolar. The FDA allows this special kind of approval based on early data on the condition that the drug maker does another clinical trial once the drug is on the market to prove it really works. If not, the FDA could pull away cloparabine's approval.

But for nearly 18 years, the study remained incomplete. So nobody really knew if the drug worked or did more harm than good. And this drug maker isn't the only one to drag its feet. Today on the show, accelerated drug approvals and why criticism of them is crescendoed in recent years. I'm your host, Aaron Scott. I'm Sydney Lepkin, NPR's Pharmaceuticals correspondent. And you're listening to Shortwave, the Daily Science Podcast from NPR. Okay, Sydney, so let's back way, way up here.

And start with where accelerated approval came from. So why did the FDA first start allowing this? So accelerated approval actually got its start during the AIDS crisis. Think about it. Tens of thousands of people were dying. And even in the late 1980s, there was only one drug on the market. It was an antiretroviral drug called AZT for short. And it had some serious side effects like dangerous anemia.

And at its best, it only bought a little more time for AIDS patients. So five years into the epidemic and that's it, one drug? Right. And I wanted to talk to someone who really lived through all this. So I eventually got in touch with J.T. Anderson, who's now in his late 70s. And he told me that back then, he and his partner decided that they just wouldn't get tested for HIV. Because... It would be very scary if we tested positive. At that time, it was a death sentence. I don't think either one of us wanted to face that. He remembers doing these funeral slash protest marches down Santa Monica Boulevard every month because that's how often someone in his L.A. based activism community would die. Yeah, and they were protesting because it seemed like the government and the drug makers were completely ignoring the epidemic because it mostly affected gay and bisexual men. So, Sydney, what about other drugs? Were they coming? They were, but not fast enough. It could take 10 years or more to develop a new drug and get it on the market.

But people around J.T. were dying all the time. So in 1988, he traveled with members of the LA chapter of the advocacy group Act Up to FDA headquarters outside Washington, D.C., for one of the group's biggest protests yet. The activists were demanding that the agency get more HIV drugs onto the market and faster. There were employees at the window, and many of them were cheering, and many of them were waving. so there was some encouragement that, you know, they were trying to say, we're with you. So fast forward to 1991, when a second HIV drug named DDI won FDA approval using a new approach. Okay. Instead of waiting to find out whether the patients taking the drug lived longer, which is sort of the gold standard of FDA drug approvals,

the FDA based its approval on something that took less time to study. In this case, it was how the medicine affected a kind of white pill. blood cell. The FDA ultimately allowed the approval, but the drug maker had to commit to finishing two clinical trials that were already underway. And if those trials didn't confirm efficacy, the pharmaceutical company agreed to withdraw the drug from the market. Sydney, when you put it in the context of the AIDS epidemic, I totally understand the logic of accelerated approvals. I mean, these patients were taking a risk, but their other option was most likely death. Meanwhile, we would eventually know for sure whether the drug works because that's the promise.

Right. And that was the first unofficial accelerated approval. The next year, the FDA formalized the process in a regulation based on that second HIV drug experience. And that ushered a bunch of HIV drugs onto the market, giving patients options. And because the confirmatory trials were already underway, they were finished pretty quickly and the accelerated approvals got converted to regular. approvals. The drugs worked. But that's not really universal, at least not anymore. Yeah. I mean, that's definitely not what happened with the chemo drug that Michael took that you mentioned earlier. Exactly. So I took a look at 30 years of FDA and NIH data to see what was going on with all the unconverted accelerated approvals. And Aaron, I found that of the currently outstanding studies required, 42% or 50 studies either took more than a year to begin

following accelerated approval or they hadn't started at all. Wow. 19 of those required studies still haven't started three years or more after accelerated approval. Four of them haven't started more than 10 years later. Wow. So they get this speedy approval in the name of helping patients, and then they're just asked to do another study to make sure the drug really works, but they don't even start that study for sometimes years?

Correct. But the regulation we talked about that, established accelerated approvals in 1992, said that studies should usually already be underway at the time of approval. So, Sydney, when you were doing your reporting, what was the reaction you were getting from people you were talking to about it? Well, Greg Gonzalez, a Yale professor, called our findings a sign that the accelerated approvals process is fundamentally broken. And this is coming from an activist pushing for faster approvals during the AIDS crisis. We're like, the FDA is killing us. Those are the things we were chanting. You know, as we took over the

FDA in late 80s. But, you know, by the early 90s, we're like, oh, my God, you know, we, we opened the Pandora's box. Pandora's box. So, Sydney, isn't there like a deadline? I mean, why are these studies taking so long? So remember that phrase studies should, quote, usually be underway? Uh-huh. The FDA told me the word usually is the problem. Okay. So when I was talking to Dr. Jack Corrigan, Corrigan, Coray, who works at the FDA Center for Drug Evaluation and Research, which is basically the part of the FDA that approves drugs. She told me that the agency would like to always have these confirmatory studies already underway at the time of the accelerated approval.

But there's really no firm regulatory requirement. We don't have the authority to stop the approval. You know, if you have the data and it meets accelerated approval, and there's this on medical need, we need to go forward. She said that most accelerated approvals do eventually go on to be converted to regular approvals or withdrawn, and that only around 10% are still waiting for evidence after five years. Yeah, but 10% seems like a big deal if you're one of those patients waiting for information and trying to make an impossible choice like Michael's mom. Do these patients at least get like a discount on the drugs that haven't been proven to be effective yet? No. The FDA has no say over prices. So once it okays a drug to get on the market, the drug, the drug,

drug maker can set the price wherever it wants. Not only that, but when I reached out to GoodRX, which is a website that helps patients get discounts on drugs and also does research, they took a look at accelerated approvals versus other drugs and actually found that there were more drug price hikes among accelerated approval drugs, 26% more over 10 years. Wow. Okay. And where does this leave people like Michael and his mom who need to make decisions about treatment now? I mean, it can leave them in a really tough spot. When I told Christy, Michael's mom, that Clolar hadn't been shown to extend patients' lives, she was surprised. She said, it's possible she just doesn't remember his doctors telling her that. But even if she knew that there were missing pieces in the evidence

backing Clofarabine, the generic name for this last resort chemo Michael got, she said she would have still wanted it for him because he was out of options. It's just kind of this big, ugly circle that no one wants to be in because, you know, damned if you do, damned if you don't. So, Sydney, it's been 18 years since clofarabine got accelerated approval. What's going on with the study that was supposed to confirm that it works? So until recently, the FDA's record about the study called it delayed, but said the drug maker planned to submit alternate study data. Its most recent new deadline was listed as December 31st, 2019. This week, the drug was finally converted to a regular.

approval after 18 years. The drug maker, Sanofi, which acquired the company that made chlofine more than a decade ago, told us that it's working with the FDA to fulfill its promise to do the study. Dr. Mikhail Seckeres, a former chair of the panel of experts that gives the FDA advice about cancer drugs, says drug makers are partially to blame. They're committing to doing this, and they're failing our patients by not completing these trials to at the very least confirm the initial benefit seen in a limited population of patients to gain accelerated approval. On the other hand, it is also on the FDA to police this. However, a withdrawal based on the absence of a study could be devastating if the drug, in fact,

really does improve overall survival or even if it just makes patients feel better. Sydney, thank you for digging into the data and bringing us this story. Thanks for having me on your show. To learn more about other patients' experiences with accelerated approvals, check out Sydney's full story. We've got a link to it in our episode notes. This episode was produced by Burley McCoy, edited by Rebecca Ramirez and Scott Hensley, and fact-checked by Rachel Carlson.

The audio engineer was Gilly Moon. I'm Aaron Scott. Thanks for listening to Shortwave from NPR. Thank you.