Hemophilia: New Treatments for an Old Disease

By Sonya Collins
WebMD Health News

Reviewed by Brunilda Nazario, MD

Jan. 12, 2016 -- Although it's been nearly a century since hemophilia was considered an early death sentence, treating it can be time-consuming and troublesome. Many people with the blood disease give themselves frequent drug infusions to keep their condition under control, sometimes as often as several times a week.

Several newly approved medications, while far from a cure, aim to lift some of that burden. Some will allow patients to go longer between treatments. Another drug in development aims to overcome a problem with current treatments, which can sometimes stop working for people whose bodies become resistant to them.

"There's never been a time when the pipeline is as full as it is now," says Nigel Key, MB, ChB, a hematologist and director of the Hemophilia and Thrombosis Center at the University of North Carolina. "I think it's a reflection of the ability of biotechnology to bring these things forward."

Two Types of Hemophilia

About 400,000 people worldwide -- including about 20,000 Americans -- have hemophilia, a bleeding disorder that slows the blood-clotting process.

People who have the condition are missing or low in one of two proteins, also called clotting factors, that work to make blood clot. A person who has the condition bleeds more than someone without it. The disease is either hemophilia A or B, depending on which clotting factors you're missing.

Last month, the FDA gave the green light to Adynovate, a new drug for people with type A. This comes on the heels of two other hemophilia drugs approved in 2015 - Nuwiq for hemophilia A and Ixinity for B. At least four other meds -- three for A and one for B -- are expected to follow in 2016.

Current Treatment and Challenges

Hemophilia can cause excessive bleeding after minor injuries. It can also lead to spontaneous internal bleeding into the joints, muscles, or organs, which can damage joints and cause other potentially life-threatening problems.

Those with the disease keep it under control by giving themselves shots of the appropriate protein. Depending on the severity of their condition, they may need injections only when bleeding happens. This type of treatment is called "on demand." Or they may give themselves regular infusions to prevent bleeding. "The goal is to get the bleeds down to two or less a year," Key says. "It's basically eliminating bleeds."

Nuwiq was approved in September as another treatment option for hemophilia A, and Ixinity as a type B treatment.

While preventive or "prophylactic" infusions that take up to 15 minutes can get rid of bleeds, they can be very inconvenient. People with hemophilia B may need them twice a week, while those with type A may need them as often as every other day, says Steven Pipe, MD, a pediatric hematologist with the University of Michigan Health System.

Another challenge is that people can become resistant to the clotting factor in the drugs. About 20% to 30% of those with hemophilia A, and 1% to 6% of people with type B, develop antibodies called "inhibitors," which make the treatment ineffective.

The newest treatments aim to address some of these issues.

Longer-Lasting Clotting Factors

The recently approved Adynovate (antihemophilic factor [recombinant], PEGylated) and another unnamed drug awaiting approval may last longer in the bloodstream than previous versions of the proteins. This will extend the time between infusions for people who use these drugs to treat hemophilia A. Drugmaker Baxalta did not release cost information for Adynovate.

These meds are "cutting down infusions from about three times a week to about twice a week," Key says. CSL Behring, the company that makes the medicine in development, thinks the FDA will approve their drug in the second half of 2016, according to a spokesperson. The company would not release cost info and has not released the drug's brand name.

The most common side effects of Adynovate are rare instances of headaches, nausea, diarrhea, and flushing. In clinical trials, the most common complaints about the yet-to-be approved drug were a stuffy or runny nose, sore throat, joint pain, and headaches.

A third drug that treats hemophilia B allows people to go as long as 14 days between infusions -- much longer than standard coverage that's been around for 20 years, Key says. Participants in small studies of this medication have not reported any significant side effects. CSL Behring also owns this drug, whose brand name it has not announced. The company expects FDA approval in the first quarter of 2016. No cost information was available.

Facing Resistance


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For some people who develop resistance to treatment, the problem resolves on its own and the medications begin to work again.

But for others, having those antibodies called inhibitors that stop a treatment from working make hemophilia very hard to control. People with persistent inhibitors can go through a lengthy, expensive treatment called immune tolerance induction. Through this treatment, you get more frequent infusions of the appropriate clotting factor -- in some cases daily -- for a year or more until your body learns to tolerate it again.

The FDA recently granted breakthrough status to ACE910, a drug that may be able to work around inhibitors. Breakthrough status helps fast-track especially promising drugs on the road to approval.

ACE910 isn't a clotting factor, but it pretends it is one. It helps blood clot in people with hemophilia A. In a clinical trial, the most common side effect was minor skin irritation where the drug was injected.

Pipe says that about 25% to 30% of patients develop resistance to treatment. So any discovery that might lower the risk is something to be excited about, he says.

Waiting for Gene Therapy

While protein infusions have been the mainstay of hemophilia treatment for decades, researchers have been working toward another treatment that could correct the genetic flaw that causes the condition. Hemophilia is caused by a defect in genes in the liver.

With gene therapy, people with the condition could get one or more infusions of the clotting-factor genes to their liver. The idea is that the genes would reproduce, become a part of the patient's body, and begin making the needed clotting factor at normal or greatly improved levels.

It could still be a decade before gene therapy is an FDA-approved treatment that doctors can offer their patients, Key says. He says there's also a risk that there might be some problem with gene therapy 10 or 20 years down the road. In the meantime, protein treatments keep getting better.

Those might work just as well without the potential risks, he says. The choice, when people have it, will be up to each person.

"The variety of needs and severity among [people with hemophilia] is so wide that I don't think there's one winning strategy," Pipe says. "I'm optimistic that gene therapy could convert many patients with severe disease to mild disease, but that wouldn't necessarily completely resolve the need for intermittent infusions or some degree of [prevention]."

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SOURCES: News release, FDA. Nigel Key, MB, ChB, FRCP, Harold R Roberts Distinguished Professor; Chief of the Section of Hematology in the Division of Hematology/Oncology; Director of the UNC Hemophilia and Thrombosis Center, University of North Carolina, Chapel Hill, NC. National Library of Medicine: "Hemophilia." National Institutes of Health: "How is hemophilia treated?" Steven Pipe, MD, Professor, University of Michigan Pediatric Hematology/Oncology, Ann Arbor, MI. DiMichelle, D. Treatment of Hemophilia, April 2008. News release, CSL Behring. News release, Business Wire. News release, Roche. American Society of Gene and Cell Therapy: "Hemophilia."

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