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$2.9 Million Gene Therapy For Severe Hemophilia Is Approved By FDA

WASHINGTON -- U.S. Officials on Thursday approved drugmaker BioMarin's gene therapy for the most common form of hemophilia, a $2.9 million infused treatment that can significantly reduce dangerous bleeding problems.

The Food and Drug Administration approved Roctavian for adult patients with severe cases of hemophilia A, the inherited blood-clotting disorder that can lead to bleeding after minor injuries or scrapes. It's the first gene therapy for those patients.

The IV therapy is a long-awaited alternative to current treatments, including weekly doses of a protein needed to help blood clot. Some patients take a newer, longer-acting biotech drug that replaces the protein.

BioMarin said in a statement that the FDA approval was based on a three-year study showing a 50% reduction in annual bleeding incidents among 134 patients who received the treatment. Most patients continued to respond to the treatment beyond three years, without needing regular IV infusions, the company said.

BioMarin said Roctavian's $2.9 million price tag reflects "the possibility of freedom from years" of infusions, which cost about $800,000 annually for a typical patient. The price is less than the $3.5 million announced last year for a similar gene therapy for hemophilia B, a less common form of the disease.

Like most medicines in the U.S., the new treatment will mainly be paid for by insurers, not patients.

BioMarin said it estimates about 2,500 U.S. Patients will be eligible to receive the therapy under the terms of the FDA's approval. Patients with certain underlying health problems and conditions are excluded under the prescribing information.

Hemophilia is caused by mutations that prevent the production of proteins needed for blood clotting. Hemophilia A is the most severe variant of the condition, and some patients can experience spontaneous bleeding even without any injury. Left untreated, the condition can cause bleeding that seeps into joints and organs, including the brain.

Roctavian uses an inactivated virus, created in a lab, to deliver a replacement gene to the liver cells that produce the clotting protein. When the therapy is successful, patients can then produce the protein themselves. The label warns that rare, severe allergic reactions can occur.

Dr. Margaret Ragni called Roctavian "a major improvement in terms of reducing the burden of disease." But she notes that many patients are comfortable with their current treatments and may be hesitant to try a new gene therapy.

"I think there's a group that will want to do this, but patients need to hear what the risks and benefits are," said Ragni, who treats patients at the Hemophilia Center of Western of Pennsylvania in Pittsburgh.

BioMarin was among the first companies to begin testing an experimental gene therapy in patients more than six years ago.

The San Rafael, California-based company excluded patients with certain potentially complicating conditions, including liver disorders and resistance to the standard blood clotting protein, which often develops in some hemophilia patients. BioMarin's president for research and development, Dr. Henry Fuchs, said the company is conducting studies in some of those excluded groups to see if they can safely receive the therapy.

Another key question is how long the therapy's benefits last. BioMarin has followed the patients for more than three years and they continue to experience reduced bleeding. But levels of the clotting protein in the bloodstream fall over time, suggesting additional treatments may eventually be needed.

"Let's make sure the expectation isn't that this is taken one time, forever and it will work perfectly for the rest of your life," Fuchs said, adding "at some point we'll know a lot more about durability."

Roctavian was approved in Europe last August, but the therapy has faced pushback from government health programs over its cost.

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The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute's Department of Science Education. The AP is solely responsible for all content.

Sanofi's Hemophilia Treatment Has Efficacy, Safety Confirmed In Phase 3 Trial

Sanofi announced Sunday that Altuviiio, its hemophilia treatment, is effective and safe, according to recently released Phase 3 trial data.

The study, which focused on treating patients younger than 12 years old with severe hemophilia A, was presented at the Annual Meeting of the International Society on Thrombosis and Haemostasis in Montreal over the weekend.

In February, Altuviiio was approved by the Food and Drug Administration for "routine prophylaxis and on-demand treatment to control bleeding episodes," as well as perioperative management for adults and children with hemophilia A.

The French drugmaker said the study results show the treatment met its primary endpoint with no inhibitor development to factor VIII detected, as well as the two secondary endpoints, annualized bleeding rate (ABR) and maintenance of factor VIII activity above pre-specified levels.

There were no serious allergie reactions, anaphylaxis or embolic or thrombotic events reported.

Additionally, Sanofi highlighted the fact that once-weekly 50 IU/kg doses of Altuviiio, compared to multiple injections per week, can offer bleed protection to children and adults.

"Today's XTEND-Kids results reinforce the ability of Altuviiio to provide effective bleed protection with once weekly dosing and reinforce our commitment to developing new treatment options designed to redefine the standard of care for people living with rare blood disorders," Karin Knobe, MD, PhD, therapeutic area head of rare diseases and rare blood disorders at Sanofi, said in a statement. 

The news surrounding Altuviiio's efficacy and safety comes as competition in the hemophilia market heats up.

Late last month, promising clinical trial results for Pfizer's marstacimab put it in pole position to become the first weekly injectable treatment for patients with hemophilia B.

If the FDA greenlights marstacimab, it would provide additional market pressures to Sanofi and Roche, which have been developing drugs to treat hemophilia A for years. Despite competing with those two drugmakers as well as CSL Behring's hemophilia B gene therapy Hemgenix, SVB Securities estimated that marstacimab sales could reach $685 million by 2032. 

However, in the same analyst note, it was mentioned that "it's unclear how much of a commercial advantage" marstacimab's flat dosing would be compared to the weight-based dosing of Roche's subcutaneous Hemlibra and Sanofi's Altuviiio.

1st Gene Therapy For Severe Hemophilia A Approved

BioMarin Pharmaceutical attained the first FDA approval for a gene therapy indicated to treat severe hemophilia A. 

Roctavian (valoctocogene roxaparvovec-rvox) was approved June 29 to reduce bleeding in adults patients with the blood disorder, according to a news release from the San Rafael, Calif.-based drugmaker. 

Every year, hemophilia A affects 1 in 5,000 male births, according to the CDC. Because of the rarity of the disorder, the approval was based on a study of about 130 patients. In the trial, the drug reduced annualized bleeding rate in hemophilia A patients, on average, by 52 percent.

The drug's cost is $2.9 million.

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