Cancer researchers are testing whether a generic drug that has been used for more than 40 years to treat parasitic infections may also help fight cancer.
The tests of mebendazole are part of a growing effort to take a fresh look at old medicines to see if they can be repurposed for new uses.
I first learned about mebendazole several years back when my son came home from camp with a gross but common infection: pinworms.
My pediatrician prescribed two doses of mebendazole, and two weeks later the infection was gone.
Flash-forward a couple of years, and I was surprised to find on clinicaltrials.gov, the federal database of medical trials, that mebendazole was being investigated as a potential cancer drug.
Curious, I contacted Gregory Riggins, a cancer researcher at Johns Hopkins University who is testing the safety of mebendazole as a potential cancer treatment. He invited me to his lab in Baltimore.
Riggins took me inside and showed me cages of cancer research mice. A few years back, he said, his idea to test mebendazole started here.
Some of the lab animals got infected with pinworms, the same parasite my son had. The veterinarian at Johns Hopkins treated the whole colony of mice with an animal version of mebendazole.
The drug staved off the parasite, but it also did something surprising. Before the mice were treated for pinworms, Riggins and his team had implanted cancer cells into the animals' brains.
But after the mice got the pinworm drug, the cancers never developed. "Our medulloblastoma stopped growing," Riggins says. He found out that other researchers were conducting animal studies to see if the drug had effects on lung cancer and melanoma.
So he got funding to do two Phase 1 studies to test whether mebendazole is safe to use in brain cancer patients, one in children and another in adults. So far the drug appears to be safe and well tolerated by patients, Riggins says. That would be expected, given that it has been used for decades around the world to treat pinworms.
"Based on the preclinical studies it looks like it has promise," says Tracy Batchelor, director of the division of neuro-oncology at Massachusetts General Hospital, who is not involved in the research. "The next step is to look for a benefit in a Phase 2 trial." That would test whether mebendazole has any effect on cancer in people. Riggins hopes to conduct that sort of trial in adult brain cancer patients.
At a time when it can cost a billion dollars to develop a new drug, the idea of repurposing existing drugs is appealing, according to Bruce Bloom. He's the president and chief science officer of Cures Within Reach, which has helped to fund Riggins' research.
Bloom points to research on metformin, a diabetes drug that's being looked at as a potential treatment for a dozen different kinds of cancer and also tuberculosis. A common blood pressure drug, propranolol, is also being studied.
"It's not likely that mebendazole or any other single repurposed drug is ever going to cure cancer," Bloom says. But he envisions the possibility that combinations of repurposed drugs might help the body to manage cancer.
Any use of mebendazole as a cancer drug would be years away, if it proves to work at all. Most drugs that emerge from Phase 1 trials never deliver the hoped-for benefits.
And in an odd twist to a complicated story, the cost of mebendazole in the U.S. has skyrocketed in recent years. Though it remains very affordable in most countries, the wholesale cost of a 100 mg tablet in the U.S. has risen from $4.50 in 2011 to $369 in 2016, according to Truven Health Analytics.
The dynamics that led to the price hike were in play before interest rose in the drug as a potential cancer treatment, analysts say. In 2013, Amedra Pharmaceuticals bought marketing rights to mebendazole from Teva Pharmaceuticals. It already owned rights to another key generic antiparasitic drug, albendazole.
"At that point, anyone who has had a high school or undergraduate economics course would be able to explain the price hike," says Joey Mattingly, an assistant professor in the department of pharmacy practice and science at the University of Maryland School of Pharmacy who studies generic drug pricing.
That leaves people with pinworm infections with the choice of two expensive prescription medications or cheaper over-the-counter options.
"Pinworms are exceedingly common," says Rachel Orscheln, an assistant professor of pediatric infectious diseases at Washington University and St. Louis Children's Hospital. The CDC estimates 40 million people are infected in the U.S. annually. Orscheln says the people most likely to be infected are children and people who are living in group settings such as nursing homes.
"There are certain cases where we do need to prescribe this medication," says Orscheln. But at the higher price, she says, "I'm very disinclined to prescribe [it]." She says over-the-counter drugs such as Pin-X or pyrantel, can work just as well in children, so "I'm very likely to steer people in that direction."
STEVE INSKEEP, HOST:
In Your Health on this Monday morning, cancer researchers are testing whether a cheap, safe drug that's been used for more than 40 years to treat parasitic infections might also help to fight cancer. The research is part of a growing movement to take a fresh look at old medicines to see if they have new uses. And NPR's Allison Aubrey has more.
ALLISON AUBREY, BYLINE: I happened to come across this drug called mebendazole several years back. My son came home from summer camp with this gross infection - pinworms. These are tiny, staple-sized worms that infect the intestines. They make kids feel itchy and uncomfortable. My pediatrician prescribed mebendazole, a cheap, generic drug. Two weeks later, the infection was gone.
Now flash forward a couple of years, and I was stunned to find on a research website, clinicaltrials.gov, that the same medicine, mebendazole, was being investigated as a cancer drug. Curious, I reached out to Greg Riggins at Johns Hopkins University. He's a cancer researcher there. He's testing the mebendazole in brain cancer patients, and he invited me to Baltimore to talk about it.
GREG RIGGINS: Here is the laboratory.
AUBREY: Tell me where we're standing, what we have in front of us.
RIGGINS: So we have cages of mice. These are our cancer research mice.
AUBREY: A few years back, something extraordinary happened here. Some of the lab animals got pinworm, the same thing my son had, and the veterinarian at Hopkins treated the whole colony of mice with the animal version of mebendazole. The drug staved off the parasite, but it also did something else. Now remember, these are lab mice that are used for experiments. Researchers had implanted cancer cells from a tumor called medulloblastoma into the animals' brains. But after they got the pinworm drug, the cancers never developed.
RIGGINS: Our medulloblastoma stops growing.
AUBREY: This was completely unexpected.
RIGGINS: We were surprised.
AUBREY: But after doing some research, Riggins realized he was not the first to see the anti-cancer properties of mebendazole. There were already researchers who were doing animal studies to see if the drug worked against lung cancer and melanoma. So Riggins decided to take his research to the next level - in people. He got funding to do a study to see of mebendazole might help people with glioblastoma, one of the most common and aggressive brain cancers. Phase one of the trial has wrapped up, and he has some initial results.
RIGGINS: The data, to me, looks as good as it could get for a phase-1 trial.
AUBREY: Now, mebendazole is not a miracle cure. But Riggins says the drug seems to interfere with cancer cells in a variety of ways. For example, it disrupts the development of blood vessels, which can starve tumors of the blood supply they need to thrive. So he says the next phase of this trial will be to find out if the drug can actually buy very sick patients more time.
RIGGINS: The odds would favor that it is increasing survival.
AUBREY: He stresses the initial data are preliminary. But Riggins says what he has learned about mebendazole has made him think it might have another role to play in fighting cancer. For example, it's possible it could help prevent the development of certain tumors. He is studying a hereditary form of colon cancer. He's already published a study showing mebendazole has a preventive effect in lab animals. Now he's planning a study to test this in people at high risk.
RIGGINS: If you can prevent a cancer, you don't have to worry about, you know, the heroic efforts to try to cure it. I mean, a cancer that never happens is the best kind of cancer.
AUBREY: In addition to the trials in Baltimore, other labs around the country and in Mexico are studying the potential of mebendazole to prevent or treat other cancers. And Bruce Bloom, who is the president and chief science officer of a group called Cures within Reach, which helps to fund the research, says he has proposals for more studies sitting on his desk.
BRUCE BLOOM: We're very optimistic that mebendazole has a potent anti-cancer mechanism.
AUBREY: And it certainly isn't the only existing drug that could be repurposed to fight cancer and other diseases.
BLOOM: It's amazing how many inexpensive drugs that have been around for 25 years or more, like mebendazole, have so many other opportunities to help unsolved disease patients.
AUBREY: Bloom points to research on the diabetes drug metformin and the heart medication propranolol as well as mebendazole.
BLOOM: It's not likely that mebendazole or any other single repurposed drug is ever going to cure cancer. But each one of them combined with other repurposed drugs can create a cocktail that helps the body to manage cancer.
AUBREY: In other words, the idea is to help buy people more time. He says considering it can cost a billion dollars to develop a new drug, repurposing existing drugs may help bring therapies to patients more quickly and affordably - at least that's the hope.
INSKEEP: And we've been listening to NPR's Allison Aubrey who's in our studios to continue the discussion about Your Health.
And Allison, wow. This makes me want to go rummage around in the medicine chest to see if there's some old prescription bottle we can repurpose for something new.
AUBREY: Right. There's a lot of optimism here, Steve. But I have to say there's a big concern with mebendazole, too. You heard Dr. Riggins say it's this affordable drug around the globe.
AUBREY: And it is. You can walk into a pharmacy in Mexico or in Brazil. You can buy it over the counter for a few bucks. And that used to be true here. When my son had pinworms, the cost of mebendazole in the U.S. was $3 a pill. Now - $369 a pill.
INSKEEP: The very same drug is more than 100 times more. Why is that fair?
AUBREY: The very same drug. So remember, the cancer research is very preliminary. This drug is intended for use as a pinworm drug, right? Now back in 2011, the company that made this drug, Teva, decided to pull it from the market. They decided not to sell it anymore. It actually went off the market for a few years, then the drug changed hands a couple of times.
So I reached out to this company called Impax Laboratories. They're the company that acquired mebendazole. And I said - what is going on here? You know, this drug is $3 around the globe. How can you be charging $369 for it? And they basically said to me - look, we spent millions of dollars acquiring the drug from Teva. We had to go through an approval process, so that's what the price is.
INSKEEP: Three sixty-nine.
Allison, thanks very much.
AUBREY: Thanks very much, Steve.
INSKEEP: That's Your Health - NPR's Allison Aubrey. Transcript provided by NPR, Copyright NPR.