First single-dose haemophilia B gene therapy approved by FDA

An adeno-associated virus vector-based gene therapy, Hemgenix, has been approved for adults with Haemophilia B by the US Food and Drug Administration (FDA).

Hemgenix is approved for patients who currently use Factor IX prophylaxis therapy, or who have had a serious haemorrhage, or repeated spontaneous bleeding episodes. CSL Behring will market the gene therapy at a cost of $3.5 million for a single dose, after acquiring the global rights from uniQure for $450 million in 2020.

'Gene therapy for haemophilia has been on the horizon for more than two decades,' said Dr Peter Marks, director of the FDA's Centre for Biologics Evaluation and Research. 'Today's approval provides a new treatment option for patients with Haemophilia B and represents important progress in the development of innovative therapies for those experiencing a high burden of disease associated with this form of haemophilia'.

Haemophilia B is a genetic bleeding disorder caused by low levels or deficiency in blood clotting Factor IX, a protein that is mostly produced in the liver and helps form blot clots. Haemophilia B represents about 15 percent of patients with haemophilia, affecting around 1 in 40,000 people, mostly men. Women carriers usually have no symptoms, although 10-25 percent have mild symptoms, and in rare cases, moderate to severe symptoms. Symptoms include prolonged bleeding and in serious cases, bleeding into joints, muscles, or internal organs. Current treatments involve regular, expensive intravenous infusions.

Two studies evaluated the safety and effectiveness of Hemegenix in 57 men aged between 18 and 75 years with severe or moderately severe Haemophilia B. Annualised bleeding rate was used as a measure of effectiveness. In the HOPE-B trial, the largest gene therapy trial to date, a 54 percent reduction in annualised bleeding rate was found compared to baseline seven to 18 months after the infusion, with increases in Factor IX activity levels, and the requirement for routine Factor IX replacement prophylaxis decreasing by 94 percent.

Common side effects of Hemegenix were liver enzyme elevations, headaches, mild infusion-related reactions, and flu-like symptoms. Clinicians are advised to monitor for adverse infusion reactions and liver enzyme elevations.

Hemegenix is currently the most expensive drug product on the market. The FDA has also approved two other gene therapies from Zynteglo (Bluebird bio) and Zolgensma (Novartis), priced at $2.8 million, and $2 million, for beta-thalassemia and spinal muscular atrophy, respectively. Zolgensma has also been approved by the National Institute for Health and Care Excellence (see BioNews 1098). The European Medicines Agency approved Roctavian for severe haemophilia A in August 2022 and it is currently under review by the FDA.

'We are confident this price point will generate significant cost savings for the overall healthcare system and significantly lower the economic burden of haemophilia B,' a spokesperson at CSL Behring said.