Without this pill, lots of people would be dead

25 years ago, the FDA approved a pill that would change the way scientists treat cancer … for good. The pill was called Gleevec; it was designed specifically to treat CML, chronic myeloid leukemia, and it was one of the first targeted cancer therapies available. A quarter century after approval, it’s still being prescribed, as are second, third and fourth-generation drugs that followed in its footsteps. What made it so special – and so effective? Pharmaceutical correspondent Sydney Lupkin https://www.npr.org/people/825275572/sydney-lupkin walks us through the history of the drug, and why it’s continued to change lives for decades. If you liked this episode, check out our other episodes with Sydney on accelerated drug approvals https://lnk.to/3hvV3G and the development of GLP-1 pills https://lnk.to/IkOvWA. Interested in more stories about medicine and medical treatment? Email us your question at [email protected] mailto:[email protected]. Listen to every episode of Short Wave sponsor-free and support our work at NPR by signing up for Short Wave+ at plus.npr.org/shortwave http://plus.npr.org/shortwave. See pcm.adswizz.com https://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 https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:00Speaker 00

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• 0:16Emily Kwong?

  You're listening to Short Wave from NPR.

• 0:22Emily Kwong?

  Hey, Shortwavers. Emily Kwong here with NPR Pharmaceuticals correspondent Sydney Lupkin. Hello.

• 0:27Speaker 02

  Hi, Emily. So this weekend marked a very important anniversary.

• 0:32Emily Kwong?

  Was it our anniversary? We have been friends for a long time.

• 0:35Speaker 02

  No.

• 0:36Emily Kwong?

  Oh.

• 0:36Speaker 02

  Not our friendiversary, Emily. The anniversary of a pill that revolutionized cancer care.

• 0:41Emily Kwong?

  Oh, that's way better. Not that I don't love you. Uh, what pill?

• 0:45Speaker 02

  So the drug is called Glivek, and May 10th marks 25 years since the Food and Drug Administration first approved it.

• 0:51Emily Kwong?

  Okay. So Glivek, why is this pill such a big deal?

• 0:55Speaker 02

  Well, it's considered one of the first targeted cancer therapies. And what it really did was make some cancers that were once fatal not so fatal anymore, survivable.

• 1:06Emily Kwong?

  Wow, that is a big deal.

• 1:07Speaker 02

  Yeah, and I talked about it with this guy in Atlanta. His name is Mel Mann. And he told me that in 1995, he was dealing with some back pain and fatigue, but it wasn't really clear why. Then, after an MRI showed what was going on with his bone marrow, he was diagnosed with chronic myeloid leukemia, a kind of blood cancer. He was 37 at the time and had a five-year-old daughter at home. The doctors told him he had three years to live.

• 1:34Speaker 03

  Yeah, I was shocked because, you know, that's the first time that I had to face my own mortality.

• 1:41Speaker 02

  But Emily, Mel is actually still here.

• 1:45Emily Kwong?

  That is amazing. After being given only three years to live. So how, how did that happen?

• 1:50Speaker 02

  So after his diagnosis in January 1995, Mel starts doing bone marrow drives, hoping to find a match and get a lifesaving bone marrow transplant. Yeah. But at the time, if you were black, you had such a low chance of finding a match that he knew it was kind of an impossibility.

• 2:06Speaker 03

  And I would take my daughter with me. So she understood that I needed a match to live. In fact, one of the drives, she couldn't remember when, probably still five. She says, Daddy, I can't see why you can't find a match. All the blood looks the same to me.

• 2:26Speaker 02

  But after all this searching, Mel added thousands of people to the registry, but he didn't find a match for himself.

• 2:33Speaker 03

  Immediately, you're going to think of your family. And I thought, you know, how old she's going to be when, at the end of three years. And it was eight years. And I was trying to bargain for more.

• 2:46Speaker 02

  So he started participating in clinical trials for experimental treatments still in development. They would work for a few months and then stop. He outlived his expiration date, but wasn't doing well.

• 2:57Speaker 03

  By then, I was like really tired. I would sleep for eight hours, drink two cups of coffee, wake up and feel like I never went to bed. And we kind of like really lost a lot of weight. So I asked the doctor, were there any more drugs?

• 3:11Speaker 02

  And there was another one, Gleevec, though, of course, it was still being studied and didn't have that name yet. Mel started the drug in August of 1998. By the next June, Emily, he was running a marathon in Anchorage, Alaska.

• 3:26Speaker 03

  And I did it in a pretty decent time, too.

• 3:29Speaker 02

  Today on the show, Gleevec and how it ushered in a new era for cancer care. You're listening to Short Wave, a science podcast from NPR.

• 3:42Speaker 04

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• 5:01Emily Kwong?

  Okay, Sydney, today we are talking about a revolutionary cancer drug. Developing a new drug, of course, is not easy. So what is the origin story of this one, Gleevec?

• 5:12Speaker 02

  Yeah, so it kind of starts with a setback. Oncologist Brian Drucker had this idea that at the time was really new in cancer medicine. He thought, what if, instead of just trying to kill cancer cells and hoping that the healthy cells were mostly spared, you could target the reason that cancer cells were growing out of control in the first place?

• 5:34Speaker 05

  What I saw with chemotherapy is that we were giving patients pretty toxic drugs. We didn't quite know if they'd work. And my view was there had to be a better way. And that better way had to be based on a knowledge of what was driving the growth of a specific cancer.

• 5:52Emily Kwong?

  I mean, it makes total sense and is a pretty widely accepted idea now. But you're saying back then, no one had ever tried this kind of targeted approach before?

• 6:02Speaker 02

  We didn't because we didn't know what to target. There was a lot we didn't understand about cancers. And we learned it in chronic myeloid leukemia, which became one of the first cancers to be linked to a genetic abnormality, the Philadelphia chromosome. Scientists knew that people with this chromosome had a fused gene. That gene results in an abnormal enzyme that regulates one of the on/off switches for certain cell growth. This one gets stuck in the on position, leading to uncontrolled white blood cell growth, chronic myeloid leukemia. Brian was trying to turn that switch off. So he wanted to find a drug that would inhibit the abnormal enzyme.

• 6:43Emily Kwong?

  That's brilliant. Yeah.

• 6:45Speaker 05

  The problem was, not a lot of people believed that was going to work.

• 6:49Speaker 02

  He said that his institution thought it was an interesting idea for a grant or something, but he ultimately had to leave his job in Boston and move across the country to Oregon Health and Science University to really actually pursue it.

• 7:05Emily Kwong?

  Yeah, he's like, this is big science. I gotta take a risk here. Was it worth it?

• 7:10Speaker 02

  Well, he says that within six weeks of arriving, he was testing five compounds from the drug company that would become Novartis in his lab. One of them was Glivek. It was a compound discovered by scientist Nicholas Lyden, and it worked, at least in the lab.

• 7:29Speaker 05

  The reality is, I wasn't just a researcher. I also had patients, many, many patients who believed in me, thought that this was a potential way forward for them. And it allowed me to have enough courage to be their, their mouthpiece and voice to lobby to get this drug into clinical trials.

• 7:47Emily Kwong?

  So it sounds like he was in a race against time, really, to try to save these patients' lives.

• 7:52Speaker 02

  Yeah, exactly. And these trials were also unique because they only included patients with this specific kind of leukemia.

• 8:00Emily Kwong?

  Wait, so was that uncommon in cancer drug trials?

• 8:03Speaker 02

  No. Before this trial, cancer drug studies would include patients with all kinds of cancer. And they just sort of hoped that the drug worked for some of them.

• 8:11Emily Kwong?

  They would just lump them all together?

• 8:13Speaker 02

  And for a few, it would become the standard of care. It would work. But for most people, the drug wouldn't work.

• 8:18Emily Kwong?

  That's so interesting. But I guess Brian's trial, he wanted to focus just on this type of leukemia because his pill was designed to target that cancer and the thing causing the cancer.

• 8:30Speaker 02

  Exactly.

• 8:31Emily Kwong?

  Yeah.

• 8:31Speaker 02

  Within six months, every CML, which is the abbreviation for chronic myeloid leukemia, patient taking more than 300 milligrams responded to the treatment.

• 8:42Emily Kwong?

  Every patient?

• 8:42Speaker 02

  It was unheard of, Emily. And because it was 1999, it was also the early days of blogging and internet chatroom. So the patients were talking to each other.

• 8:56Speaker 05

  So all of a sudden, I was getting contacted by patients from around the world who wanted to enroll on this clinical trial.

• 9:04Speaker 02

  They knew that they had to scale up trials and get the drug application to regulators and like, fast. And that's where the folks at Novartis come in.

• 9:12Emily Kwong?

  That's the drug company, right?

• 9:14Speaker 02

  Right. So the next step would be for a drug company to take the drug to the FDA for approval. To do that, you've got to look at the data and prepare a whole package. Enter Insa Gothman, who was right out of school and got hired as a biostatistician.

• 9:28Speaker 06

  And it was apparent back then that this is a game changer and that we needed people with energy who could make this drug development even faster and then bringing this to authorities as fast as we could.

• 9:42Speaker 02

  She became the statistical lead on the project, working long hours.

• 9:46Emily Kwong?

  What was she doing?

• 9:47Speaker 02

  So one of her jobs was to look at survival curves.

• 9:50Speaker 06

  And when I was first running them for Gleevec, I was like, OK, I must have done a programming mistake, something is wrong. Because the curves were just, I mean, they were all doing fantastic and they were all alive. And I'm like, no, no, no, something is wrong. This can't be, can't be right.

• 10:07Emily Kwong?

  But it was right.

• 10:08Speaker 02

  Yeah. So Gleevec was able to switch the enzyme to the off position, shutting down that cell overgrowth, which let patients' white blood cell counts return to normal.

• 10:19Emily Kwong?

  This is so inspiring.

• 10:20Speaker 02

  Mm-hmm. And when Gleevec was approved on May 10, 2001, it was the fastest approval at the time. Seventy-two. Two days and everyone from the NIH to the FDA to the HHS secretary to the company executives wanted to take a bow. Amit Serpatori is an assistant professor of population medicine at Harvard Medical School and he says it was an example of the public and private sectors working together at their best to bring forward meaningful medical advancements.

• 10:50Speaker 07

  We have one of the most robust innovation systems in the world and that system in pharmaceuticals really relies on early-stage funding by the government of science, of medical research.

• 11:10Speaker 02

  And Emily, none of this would have happened without people knowing about the genetic mutation that causes this cancer in the first place, the Philadelphia chromosome. That discovery was funded by the National Cancer Institute, which is part of the NIH.

• 11:23Emily Kwong?

  So this, even though it got approved in 72 days, that's because of years of work ahead of it and layers of cooperation from so many different groups.

• 11:34Speaker 02

  Cooperation and taking on risk. Remember, Brian Druker moved across the country. The drug company that would become Novartis took on the financial risk of doing the expensive clinical trials. The patients took a risk trying a new drug and then a whole bunch of people moved to heaven and earth to speed up the approval time. All of this changed medicine.

• 11:55Speaker 07

  You can think of it as really ushering in this era that we have now of targeted therapies, targeted cancer drugs on the market. There's now over 100 targeted cancer drugs on the market, which in many cases have meaningfully improved the overall survival and quality of life.

• 12:17Speaker 02

  Though I should add that Gleevec was also considered incredibly expensive when it launched at $26,000 a year. And that meant even more money back in the early 2000s.

• 12:26Emily Kwong?

  Yeah.

• 12:27Speaker 02

  The drug is now generic and much cheaper.

• 12:30Emily Kwong?

  So Gleevec is still being used today.

• 12:33Speaker 02

  Yep, it's still used. Brian still prescribes Gleevec and the second, third and fourth gen- Generation drugs that came after and he's still able to tell patients that they'll be able to live a normal life. He told me about one patient who had leukemia as a child and started taking Gleevec. Eventually, she was able to come off the drug with no recurrence of her cancer, and she now has two kids.

• 12:57Speaker 05

  Her parents thought that she would never live long enough to graduate from high school. And here she is with us today.

• 13:04Speaker 02

  And the researchers kept studying Gleevec and they found out it actually works for other cancers. For example, it can also treat a certain kind of gastrointestinal tumor by shutting off its out of control growth. Dr. Drucker, Brian remembers that he had this one patient who had one of these tumors that he said made his stomach look like he was nine months pregnant, and he was uncomfortable, he couldn't roll over in bed, he was miserable. And within days of starting Gleevec, Brian got a call. The patient was on the other end of the line and he said he felt so great that he was playing a round of golf.

• 13:41Emily Kwong?

  Because Gleevec was able to like turn off the cell growth?

• 13:44Speaker 02

  Uh huh.

• 13:44Emily Kwong?

  Wow. And Cindy, in marking the anniversary of Gleevec this week, where is everyone at now? All the people who helped make this possible? Like, um, that Swiss biostatistician?

• 13:56Speaker 02

  Insa, she stayed at Novartis and became the executive director in biostatistics, and she's about to retire.

• 14:02Emily Kwong?

  And what about Mel, the dad?

• 14:03Speaker 02

  Mel, the dad, given three years to live in 1995. He's now 69 years old.

• 14:08Emily Kwong?

  Wow.

• 14:08Speaker 02

  Yeah, he got to watch his daughter grow up. He even went back to school and got a second bachelor's degree, and he wants to run the Boston Marathon next.

• 14:16Emily Kwong?

  Heck, yeah.

• 14:17Speaker 03

  I'm just thankful for the physicians who I know had to burn a lot of midnight oil to make it happen. And the researchers and, and people who were involved in the whole process. You know, the people at the sites, the, uh, people who crunched the numbers and just so many people that I have to be thankful for. So it means a lot, you know, I got a second chance at life.

• 14:42Emily Kwong?

  Yeah. And what about Brian Drucker, the oncologist who really is responsible for a lot of this and figured out Gleevec?

• 14:49Speaker 02

  Yeah, he developed it. He's gotten to watch people given a death sentence actually go on to live normal lives. And some of them celebrated Gleevec's anniversary with him this past weekend.

• 15:00Speaker 05

  It is a remarkable and magic moment of reflection because some of the patients on that phase one, first in human trial, are still with me. And they've seen weddings, births, graduations, grandchildren, all the things that they never thought that they could imagine would happen.

• 15:26Emily Kwong?

  Sydney, thank you so much for sharing this story and the science behind it.

• 15:31Speaker 02

  Thank you for having me.

• 15:33Emily Kwong?

  If you liked this episode, share it with a friend because it really helps the show out. Also, check out the episode we did with Sydney on accelerated drug approvals and the development of the GLP-1 pills. This episode was produced by Hannah Chin. It was edited by Rebecca Ramirez. The fact checker was Tyler Jones. Jimmy Keely was the audio engineer. I'm Emily Kwong. Thank you for listening to Shore Wave from NPR.

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