Gene Therapy Shows Promise For Hemophilia, But Could Be Most Expensive U.S. Drug Ever

Jack Grehan, who was born with hemophilia, used to inject himself every couple of days with a protein he needs for his blood to clot. But not anymore.

"It's been absolutely brilliant and life-changing for me," says Grehan, 26, of Billinge in North West England. He received an experimental gene therapy in 2017 that, at least for now, has eliminated his need for regular injections. "I can just go about my day and not have to worry."

Based on experiences like Grehan's, the company that developed the therapy is seeking approval in Europe and the United States to start selling the first gene therapy for hemophilia. That's generating excitement among patients, patient advocates and doctors.

"Not to have to worry about hemophilia any longer — I think it's essentially transformational for many patients," says Dr. John Pasi of the Royal London Hospital and the London School of Medicine and Dentistry. Pasi led the recently published study Grehan took part in.

Others are more cautious.

"This is really exciting, but also raises a lot of questions," says Meg Bradbury, director of research at the Hemophilia Federation of America, a patient advocacy group.

One of the biggest questions is the possible cost. BioMarin Pharmaceutical Inc. of San Rafael, Calif., the company that developed the gene therapy, says the treatment could cost as much as $3 million per patient, which would make it the most expensive drug ever approved.

"It's just outrageous," says Peter Bach, who studies drug prices at Memorial Sloan Kettering Cancer Center in New York.

Company officials defend the possible price, however. It currently costs hundreds of thousands of dollars a year to treat each hemophilia patient. The gene therapy would, researchers hope, be a one-time treatment that lasts a lifetime.

"The context is this gigantically expensive disease to treat," says Jeff Ajer, BioMarin's executive vice president and chief commercial officer. "It's likely that our gene therapy would save a lot of money — millions, perhaps many millions."

Hemophilia is a relatively rare condition. Hemophilia A, the most common form of the disease, occurs in 1 of about every 5,000 boys. (Though girls can be born with hemophilia, too, that's much rarer.) People born with the condition are missing a crucial protein that their blood needs to clot. So doing things as simple as walking can cause dangerous bleeding in their joints that eventually can be crippling.

"It was quite difficult, because I was always getting these bleeds in the ankles," Grehan says. "So walking around was becoming more and more troublesome."

Grehan has a severe form of hemophilia A, which causes a deficiency in a clotting protein called factor VIII.

"It's the microbleeds that just sort of wear your down — not even physically but mentally," Grehan says.

And Grehan knew that propensity to bleed could cause even more serious, possibly fatal, complications if the hemorrhage every happened in his brain or other parts of his body.

"Internally, there could have been a lot worse situations," Grehan says. "I consider myself quite lucky in that respect."

Before anything like that happened to Grehan, he learned that doctors were testing the gene therapy.

"When I first heard about the trial I thought it was unbelievable that we were in this situation — that this even existed," Grehan says. So he volunteered three years ago to let doctors infuse trillions of neutralized viruses that had been genetically engineered to carry the healthy gene he needed into his liver.

Within a couple of weeks, Grehan could stop injecting himself with the clotting protein that he had previously needed.

In fact, the treatment dramatically cut bleeding in all 13 of the patients who got the effective dose of gene therapy determined by the study Grehan was in.

"I think it's amazing data actually," Pasi says. "It's been the Holy Grail for years to be able to treat hemophilia with a gene therapy treatment. And maybe we're beginning to see that that wasn't a pipe dream — that this is a realistic option." It's the latest promising development for gene therapy, which has finally started producing effective treatments for a variety of diseases after decades of setbacks.

Several other experimental forms of gene therapy are also showing promise for hemophilia, including another type of the condition, known as hemophilia B. So far, nearly 150 patients have been treated with BioMarin's gene therapy as part of a larger study, and the results continue to be encouraging, according to the company. Some patients having been followed for as long as three years.

"For a good fraction of these people, they don't have to even think about having hemophilia anymore," says Henry Fuchs, president of research and development at BioMarin.

The Food and Drug Administration has designated the treatment a "breakthrough" therapy and accepted the company's application to give the gene therapy priority status for evaluation, representatives of BioMarin say. That makes it the first gene therapy for hemophilia the agency has agreed to consider.

According to the company, the FDA has signaled it will make its decision by Aug. 21 about whether to approve the treatment for sale.

Longer studies will be need to determine if the treatment is, in fact, a one-time, therapy for lifelong effect, experts say.

"It seems to be working very well, but we are only at three years," says Dr. W. Keith Hoots, director of the division of blood diseases and resources at the National Heart, Lung and Blood Institute. "We need to know for sure whether it will extend for their entire life. And only time will tell for that."

Nevertheless, Bach agrees the treatment appears very promising. Still, he questions the price tag, which would be just the latest in what appears to be an ongoing rise in the cost of the new wave of genetic therapies.

"The clinical breakthrough is prodigious. We should be thrilled by it," Bach says.

"But the greatest innovation by the pharmaceutical industry is not the biologic breakthroughs they're making," he says. "It's their ability to extract money from society that we could put into other things — like better benefits in Medicare, lower out-of-pocket costs for poor people, dental coverage and things like that."

The prices of the drugs already used to treat hemophilia are inflated, Bach argues.

Bradbury, from the Hemophilia Federation of America, agrees cost is a concern.

"We need to make sure all those who are eligible would have access to it," Bradbury says.

Ajer says the company has already been negotiating with insurance companies and government programs to cover the costs.

"Our work is not done here, but my expectation is that most of the patients who need access to therapy would be able to get it, in not a terribly long time, through their insurance system," Ajer says. As someone who has had to deal with hemophilia all his life, Grehan thinks the price is reasonable.

"I think $3 million for this is very cheap — because it is life-changing," Grehan says. "And if you're going to spend hundreds of thousands of dollars a year over a lifetime, that seems worth it to me." [Copyright 2020 NPR]