Factor IX(Sangamo Therapeutics, Inc.)

The National Institute for Health and Care Excellence (NICE) has issued a draft Appraisal Consultation Document that does not recommend CSL Behring’s Hemgenix (etranacogene dezaparvovec) gene therapy for haemophilia B. The company has been seeking approval for use of the therapy in adults with severe or moderately severe haemophilia B without a history of factor IX inhibitors. In its guidance, NICE’s evaluation committee said that while there is clear evidence that the therapy reduces the number of bleeding episodes haemophilia B patients have each year, there is not enough evidence on how well it works in the long term, meaning cost-effectiveness estimates are “uncertain”. It also cited problems with the indirect comparison between the gene therapy and factor IX replacement therapies. Haemophilia 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. Patients with moderate-to-severe haemophilia B typically require a routine treatment regimen of intravenous (IV) infusions of factor IX replacement products to maintain sufficient levels of clotting factor to prevent bleeding episodes. While these therapies are effective, patients must adhere to strict, lifelong infusion schedules. They may also continue to experience spontaneous bleeding episodes as well as limited mobility, joint damage or severe pain as a result of the disease. For appropriate patients, Hemgenix allows people living with haemophilia B to produce their own factor IX after a one-off, single dose by IV infusion. CSL’s application was supported by results from the ongoing HOPE-B trial, which showed that Hemgenix was associated with stable and durable increases in mean factor IX activity levels. Additionally, 96% of Hemgenix-treated patients discontinued routine factor IX prophylaxis, meaning they no longer required regular infusions for up to two years. The company has expressed its disappointment with NICE’s decision and said it “remains confident” in the benefit of Hemgenix for eligible patients and its potential long-term value for the NHS. Eduardo Cabas, general manager at CSL Behring UK and Ireland, said: "We firmly believe in the potential of [Hemgenix] to bring a change in the lives of eligible haemophilia B patients, offering them possible long-lasting therapeutic benefit.” Also responding to NICE’s decision, Clive Smith, chair of the Haemophilia Society said: "We are disappointed with this initial decision and hope that NICE further considers these benefits carefully and helps eligible patients to access these innovative, potentially long-lasting treatments as soon as possible.” CSL licensed the exclusive global rights to Hemgenix from gene therapy company uniQure in May 2021 and is now solely responsible for the further development, registration and commercialisation of the therapy.