You're listening to Shortwave from NPR.
Hey, Shortwavers.
Emily Kwong here with NPR Pharmaceuticals correspondent Sydney Lufkin.
Hello.
Hi, Emily.
So this weekend marked a very important anniversary.
Was it our anniversary?
We have been friends for a long time.
No.
Oh, not our friendversary, Emily.
The anniversary of a pill that revolutionized cancer care.
Oh that's way better.
Not that I don't love you.
What pill?
So the drug is called Gleevec and May 10th marks 25 years since the Food and Drug Administration first approved it.
Okay.
So, Gleevec, why is this pill such a big deal?
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.
Wow, that is a big deal.
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.
I was shocked because, you know, that's the first time that I had to face my own mortality.
But, Emily, Mel is actually still here.
That is amazing.
After being given only three years to live.
So how did that happen?
So after his diagnosis in January 1995, Mel starts doing bone marrow drives, hoping to find a match and get a life-saving bone marrow transplant.
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.
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 be more than 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.
But after all this searching, Mel added thousands of people to the registry, but he didn't find a match for himself.
Immediately, you're going to think of your family.
And I thought, you know, how old she's going to be at the end of three years.
And it was eight years.
And, you know, I was trying to bargain for more.
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.
By then I was like really tired.
You know I would sleep for eight hours, drink two cups of coffee, wake up and feel like I never went to bed and become like really lost a lot of weight.
So I asked the doctor, were there any more drugs?
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.
And I did it in a pretty decent time, too.
Today on the show, Gleevec and how it ushered in a new era for cancer care.
You're listening to Shortwave, a science podcast from NPR.
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?
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?
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 that was driving the growth of a specific cancer.
I mean it makes total sense and is amazing, a pretty widely accepted idea now, but you're saying back then no one had ever tried this kind of targeted approach before.
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 Philadelphia chromosomes.
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.
That's brilliant.
Yeah.
Not a lot of people believe that was going to work.
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.
Yeah.
He's like, this is big science.
I got to take a risk here.
Yeah.
Was it worth it?
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 Gleevec.
It was a compound discovered by scientist Nicholas Leiden, and it worked, at least in the lab.
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 mouthpiece and voice to lobby to get this drug into clinical trials.
So it sounds like he was in a race against time, really, to try to save these patients' lives.
Yeah, exactly.
And these trials were also unique because they only included patients with this specific kind of leukemia.
Wait, so was that not common in cancer drug trials at the time?
No.
Before this trial, cancer drug studies would include patients with all kinds of cancer.
And they just sort of hope that the drug worked for some of them.
They would just lump them all together?
And for a few, it would become the standard of care.
It would work.
But for most people, the drug wouldn't work.
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.
Exactly.
Within six months.
Every CML, which is the abbreviation for chronic myeloid leukemia patient taking more than 300 milligrams responded to the treatment.
Every patient?
It was unheard of, Emily.
And because it was 1999...
It was also the early days of blogging and internet chat room.
So the patients were talking to each other.
So all of a sudden, I was getting contacted by patients from around the world who wanted to enroll in this clinical trial.
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.
That's the drug company, right?
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.
Entered in Sagothman, who was right out of school and got hired as a biostatistician.
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 bringing this to authorities as fast as we could.
She became the statistical lead on the project, working long hours.
What was she doing?
So one of her jobs was to look at survival curves.
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.
But it was right.
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.
This is so inspiring.
And when Gleevec was approved on May 10, 2001, it was the fastest approval at the time, 72 days.
And everyone from the NIH to the FDA, to the HHS secretary, to the company executives, wanted to take a bow.
Amit Sarpatwari 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.
We have one of the most robust innovation systems ever.
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.
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.
Cooperation and taking on risk.
Remember, Brian Drucker 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.
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 overall survival and quality of life.
Though I should add that Gleevec was also considered incredibly expensive when it launched, at 26000 a year.
And that meant even more money back in the early 2000s.
Yeah.
The drug is now generic and much cheaper.
So Gleevec is still being used today.
Yep.
It's still used.
Brian still prescribes Gleevec and the second, third and fourth 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.
Her parents thought that she would never live long enough to graduate from high school.
And here she is with us today.
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.
Because Gleevec was able to, like, turn off the cell growth?
Uh-huh.
Wow.
Sydney, in marking the anniversary of Gleevec this week, where is everyone at now?
All the people who helped make this possible.
Like, that Swiss...
Biostatistician.
INSA.
She stayed at Novartis and became the executive director in biostatistics and she's about to retire.
And what about Mel, the dad?
Mel, the dad, given three years to live in 1995.
He's now 69 years old.
Wow.
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.
Heck yeah.
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 people who were involved in the whole process.
You know, the people at the sites, the 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.
Yeah.
And what about Brian Druker, the oncologist, who really is responsible for a lot of this and figured out Gleevec?
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 Gluvec's anniversary with him this past weekend.
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.
Sydney, thank you so much for sharing this story and the science behind it.
Thank you for having me.
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 ShoreWave from NPR.
