Updated: FDA Approves $3.5 million Gene Therapy Hemgenix for Hemophilia B

The FDA has approved CSL Behring’s Hemgenix (etranacogene dezaparvovec) to treat adults with hemophilia B who currently use factor IX prophylaxis therapy, or have current or historical life-threatening hemorrhage.

Hemophilia B is a rare, lifelong bleeding disorder caused by a single gene defect, resulting in insufficient production of factor IX, a protein primarily produced by the liver that helps blood clots form. Treatments for moderate-to-severe hemophilia B include prophylactic infusions of factor IX replacement therapy to temporarily replace or supplement low levels of blood-clotting factor.

Peter Marks, M.D., Ph.D.

“Gene therapy for hemophilia has been on the horizon for more than two decades. Despite advancements in the treatment of hemophilia, the prevention and treatment of bleeding episodes can adversely impact individuals’ quality of life,” Peter Marks, M.D., Ph.D., director of the FDA’s Center for Biologics Evaluation and Research, said in a press release.“Today’s approval provides a new treatment option for patients with Hemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of hemophilia.”

Hemgenix is an adeno-associated virus vector-based gene therapy and is a one-time product given as a single dose by IV infusion. The therapy uses an adeno-associated virus as a vector that carries the Padua gene variant of Factor IX, which generates factor IX proteins. The gene is expressed in the liver to produce factor IX protein to increase blood levels of factor IX to limit bleeding episodes.

CSL Behring, a CSL business, will begin commercializing Hemgenix as soon as possible in the United States with a list price of $3.5 million, according to a company spokesperson. "We are confident this price point will generate significant cost savings for the overall healthcare system and significantly lower the economic burden of hemophilia B by reducing annual bleed rates, reducing or eliminating prophylactic therapy and generating elevated FIX levels that last for years," she said. "This price was determined with consideration of the clinical, societal, economic and innovative value represented by this novel gene therapy and was designed to support patient access to this new treatment paradigm."

In a report released earlier this month, the Institute for Clinical and Economic Review indicated that cost savings from etranacogene dezaparvovec for hemophilia B, as well as from valoctocogene roxaparvovec for hemophila A, will come from offsetting the costs of prophylactic infusions of factor IX replacement therapy.

ICER had used a placeholder price of $4 million in its analysis of etranacogene dezaparvovec and capped the offset costs at $150,000 a year. They found that to be cost-effective and achieve a Health Benefit Price Benchmark (HBPB), etranacogene dezaparvovec would need to be priced at $2.93 million to $2.96 million. ICER researchers also noted that there is still uncertainty about the long-term net benefits compared with factor IX replacement therapy and the impact of the gene therapy on liver function and the risk of hepatocellular carcinoma. Elevated liver enzyme was seen in 16.7% of patients and required treatment with corticosteroids.

ICER’s HBPB is a price range based on the amount of improvement in overall health patients receive from that treatment, when a higher price would cause disproportionately greater losses in the health system due to rising overall costs.

The FDA approval is supported by results from the ongoing HOPE-B trial, the largest gene therapy trial in hemophilia B to date. Results from the study demonstrated that Hemgenix allowed patients to produce mean factor IX activity of 39% at six months and 36.7% at 24 months post infusion. Seven to 18 months post-infusion, the mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by 54% compared with the six-month lead-in period on factor IX prophylactic replacement therapy.

Steven Pipe, M.D.

In addition, 94% of patients treated with Hemgenix discontinued use of prophylaxis and remained free of previous continuous routine prophylaxis therapy. The most common side effects (incidence ≥5%) were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea and feeling unwell.

“Hemgenix is unique in its approach to increasing mean factor IX activity and hemostatic protection in those with hemophilia B, and today’s approval could fundamentally transform the treatment paradigm for this life-long condition,” Steven Pipe, M.D., said in a press release. He is professor and the Laurence A. Boxer Research Professor of Pediatrics and professor of Pathology at the University of Michigan and a lead investigator in the HOPE-B study.

Updated to include information from ICER.