FDA Approves $3.5 Million Gene Therapy for Hemophilia B

The US Food and Drug Administration (FDA) approved Hemgenix (etranacogene dezaparvovec), the first gene therapy for Hemophilia B. A one-time treatment costs $3.5 million per dose and is the most expensive drug ever approved in the US.

Hemophilia B is a genetic bleeding disorder resulting from missing or insufficient levels of blood clotting factor IX, a protein needed to produce blood clots to stop bleeding. About 1 in 40,000 people are diagnosed with the disease, most of whom are men.

Hemgenix is a one-time gene therapy product given as a single dose by IV infusion.

Tumas Beinortas, an academic clinical fellow at the University of Cambridge, says that historically, all treatments for hemophilia B have included the external replacement of the externally synthesized factor IX. These treatments require regular infusions, which are life-saving but inconvenient and expensive.

“Gene therapy allows greater personal freedom for the patients requiring these infusions. Gene therapy also potentially ensures continuous factor IX production and at more constant levels,” he told Healthnews.

When factor IX is infused externally, it reaches its peak and gradually drops. Towards that period, the patient is most susceptible to bleeds, Beinortas explains. Meanwhile, gene therapy effectively replaces the defective gene allowing the liver to synthesize factor IX continuously.

Beinortas says that in rare cases, hemophilia B patients develop antibodies against the treatments that include external infusion of factor IX and these cases are particularly troublesome to manage. However, when the clotting factor is synthesized within the body, as in the case of gene therapy, the likelihood of the autoimmune response is reduced.

The most expensive drug

The safety and efficacy of Hemgenix were tested in two studies of 57 adult men 18 to 75 years of age with severe or moderately severe Hemophilia B.

During the first six months of the trial, participants continued on their regular prophylactic infusions of factor IX and had the average rates of bleeds calculated, Beinortas explains.

“After six months, they received the adenoviral vector infusion that encodes factor IX. Following the infusion, the bleeding rates were assessed for at least 18 months and then compared to the pre-infusion rates. The study found a significant decrease in the frequency of bleeds, which can be very debilitating for these patients,” he added.

In the study, the most common side effects were liver enzyme elevations, headache, mild infusion-related reactions, and flu-like symptoms.

Manufacturer CSL Behring set the price at $3.5 million per dose, making Hemgenix the most expensive drug in the US, as it tops Zynteglo, the first cell-based gene therapy for patients with beta-thalassemia. The treatment that costs $2.8M a dose was approved in August 2022.

However, the Institute for Clinical and Economic Review, in their independent cost-effectiveness analysis, suggested a price for Hemgenix between $2.93 million and $2.96 million.

Beinortas says that while gene therapy is being sold as providing a lifelong cure for hemophilia B, the follow-up for these patients hasn’t been long enough.

“We don’t know yet whether it is a lifelong cure or will it last for the next 5-10 years, and then the patient will need a new gene therapy infusion or to go back to prophylaxis. However, in the medium time frame, it definitely looks very promising,” he said.