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Some fast-tracked drugs are tardy doing their trials to get regular FDA approval


For decades, the Food and Drug Administration has had a way to get drugs out to patients who have an urgent need. If a drug has preliminary evidence that it's successful, the FDA will approve its use. The drug-maker is then required to conduct a fuller set of studies to make sure the medicine really works. The two-step process is called accelerated approval. But what if those follow-up studies don't get done? NPR pharmaceuticals correspondent Sydney Lupkin tackles this question in her new investigation into these fast-tracked drugs. We'll talk with Sydney in a minute. First, she has the story of one family who used a fast-tracked drug.

SYDNEY LUPKIN, BYLINE: In the summer of 2013, Michael Alcayaga 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.

KRISTI ALCAYAGA: 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 his shirt 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.

LUPKIN: That's his mom, Kristi Alcayaga of Everett, Wash. She said he didn't want to wake her up, so he fell asleep like that. Eventually, Michael was diagnosed with a serious cancer - acute lymphoblastic leukemia, or ALL. But he was optimistic. He went to school, bald head and all, and was determined to be healthy enough to play baseball in the spring.

ALCAYAGA: He goes, wow. Well, I can't wait to be able to say that I beat cancer.

LUPKIN: The cancer had other plans. Six months later, he wasn't responding well enough to treatments. Running out of options, doctors gave him a different chemotherapy that Kristi remembers Michael's doctors called the big gun.

ALCAYAGA: I don't even think that the infusion was complete, and he started puking. He had never done that with any of the other chemos.

LUPKIN: The big gun failed. Michael died in May of 2014, a few weeks after his 16th birthday.

ALCAYAGA: I mean, he walked in the hospital, and we 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 the hospital, and, you know, he never walked out.

LUPKIN: The FDA gave this chemo, called clofarabine, an accelerated approval in 2004. By FDA's rules, the drug's maker was required to do a confirmatory study to make sure the drug is effective. If not, the FDA could pull clofarabine's approval. But for nearly 18 years, the study remained incomplete.

SHAPIRO: That's NPR's Sydney Lupkin, who is with us now. And, Sydney, does this mean that the drug doesn't work?

LUPKIN: So nobody really knew if the drug worked or did more harm than good. Michael's mom Kristi says she doesn't remember being told about that, but even if she was, she still would have chosen to give it to him. Her son was out of options.

ALCAYAGA: 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, kind of, because if we hadn't done the clofarabine, I would probably be regretting it.

LUPKIN: And that tension is at the heart of the patients' and doctors' decision-making around accelerated approvals.

SHAPIRO: OK. Well, that treatment was 2014. Where is the drug-maker today with getting its full FDA approval?

LUPKIN: So the drug-maker said it was working with the FDA to get the study done and the drug's efficacy confirmed. By the way, this drug was originally made by Genzyme, but that company was acquired by Sanofi more than a decade ago. As for the FDA, it says it can't comment on specific drugs, but this week clofarabine finally got converted to a full approval. Still, clofarabine is not the only drug with a tardy trial.

SHAPIRO: How often does that happen?

LUPKIN: NPR analyzed 30 years of FDA and NIH data and found that 42% of the outstanding required confirmatory studies either took more than a year to begin following accelerated approval or hadn't started at all. Nineteen of those required studies still haven't started three years or more after accelerated approval, and four of them haven't started more than 10 years later. Yet, according to the regulation that establishes accelerated approvals, confirmatory studies should, quote, "usually be studies already underway at the time of approval."

SHAPIRO: That doesn't seem to be the case. So why is the FDA letting it happen?

LUPKIN: It's the word usually. Dr. Jacqueline Corrigan-Curay, an FDA official I talked with, is in the Center for Drug Evaluation and Research. She says the agency would like to have these studies up and running at the time of accelerated approval, but it's not a statutory requirement.

JACQUELINE CORRIGAN-CURAY: 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 medical need, we need to go forward.

LUPKIN: And approve it without the additional study started. But former FDA official Rachel Sherman, who spent three decades there, including three years as its principal deputy commissioner, says that's a problem.

RACHEL SHERMAN: The farther one gets away from the accelerated approval, the more the community that's using the drug, if they're using it, begins to think of it as just another approved drug. They don't think of it as somehow different.

SHAPIRO: Are there examples, Sydney, where accelerated approval is good?

LUPKIN: Absolutely. With the HIV drugs in the '90s, the studies were underway at the time of accelerated approval. That gave HIV patients options, and there was pretty quick proof the drugs actually worked. Even now, only around 10% of drugs with accelerated approvals are still waiting for confirmatory evidence after five years, the FDA says.

SHAPIRO: What if your drug is in that 10% bucket?

LUPKIN: Well, that leaves those patients and their doctors in a tough spot. Dr. Mikkael Sekeres, a former chair of the expert committee that advises the FDA on cancer drugs, says drug-makers are partially to blame.

MIKKAEL SEKERES: 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.

LUPKIN: However, he told me that pulling a drug off the market based on the absence of a study could be devastating if the drug, in fact, really does improve overall survival. And he said that patients taking drugs with accelerated approvals deserve timely answers.

SHAPIRO: What role does price play when it comes to accelerated versus regular FDA approval?

LUPKIN: So the FDA has no say over price. But I asked GoodRx, a company that helps people find discounts on drugs, to crunch some numbers for us. Here's Tori Marsh of GoodRx on what they found.

TORI MARSH: During the first 10 years after approval, accelerated approval drugs are more likely to have a price increase in any given year throughout those 10 years.

LUPKIN: There were actually 26% more price hikes during that time.

SHAPIRO: Is there a plan to get this program back on track closer to its original intent?

LUPKIN: People are definitely paying attention. There have been a few recent accelerated approvals that sparked public outcry. Democratic Senator Ron Wyden made sure that before he voted to confirm FDA Commissioner Robert Califf earlier this year - that he got him to commit to making fixes to accelerated approval. And the FDA itself has a few ideas for how to better enforce these trials with new legislative proposals and penalties. So there's growing pressure for changes, but we'll have to wait and see.

SHAPIRO: NPR pharmaceuticals correspondent Sydney Lupkin. Thank you.

LUPKIN: You bet.


Sydney Lupkin is the pharmaceuticals correspondent for NPR.