First gene therapy to treat haemophilia B

EMAEMA has recommended granting a conditional marketing authorisation in the European Union (EU) for Hemgenix (etranacogene dezaparvovec) for the treatment of severe and moderately severe haemophilia B in adults who do not have factor IX inhibitors (auto-antibodies produced by the immune system which make factor IX medicines less effective).

Haemophilia B is an inherited disorder characterised by an increased bleeding tendency due to a partial or complete deficiency of coagulation factor IX, a protein needed to produce blood clots to stop bleeding. The deficiency of factor IX is the result of mutations of the respective clotting factor gene. Prolonged bleeding episodes in patients with haemophilia B can lead to serious complications, such as bleeding into joints, muscles or internal organs, including the brain. Haemophilia B is a rare debilitating disease affecting approximately 1 in 20,000 to 50,000 live male newborns.

Medicines currently authorised to treat haemophilia B aim to prevent bleeding episodes or to treat bleeding episodes that may occur during surgery or in emergencies even when patients are on regular therapy. Patients require a lifelong routine treatment regimen of intravenous infusions of factor IX replacement products to maintain sufficient factor IX levels. Therefore, there is an unmet medical need for new therapeutic approaches that might free patients from the burden of frequent infusions, or episodically at the time of a bleeding event.

Hemgenix is the first gene therapy to treat haemophilia B. It is delivered as a single infusion. Etranacogene dezaparvovec, the active substance in Hemgenix, is based on a virus (adeno-associated virus or AAV) which has been modified to not cause disease in humans. The virus contains copies of the gene responsible for producing factor IX. When injected into the patient's vein, the virus is carried to the liver where the gene will be taken up into the patient's liver cells and start producing factor IX, thereby limiting bleeding episodes.

EMA's recommendation is based on the results of two prospective, open-label, single‑dose, single-arm studies, in which 57 adult male patients with moderately severe or severe haemophilia B were enrolled. In the first study, the three patients sustained positive treatment effects up to three years following the infusion. In the second study, 52 patients sustained positive treatment effects up to two years following the infusion. It is yet unknown how long the benefits of this one-time treatment will last.

Efficacy data show that the treatment significantly reduces the frequency of bleeding compared to standard care (annualised bleeding rate reduced from 4.19 to 1.51 bleedings per year after the infusion), achieves clinically relevant levels of factor IX activity, and minimises the need for prophylactic factor IX replacement therapy (96 % of subjects treated with Hemgenix discontinued use of routine prophylaxis).

The majority of reported adverse events were considered mild. Hepatotoxicity (liver damage), a common side effect due to immune reaction induced by these AAV-based gene therapies and characterised by an increase in the levels of liver enzymes called transaminases, has been reported with Hemgenix. The condition can be treated successfully with corticosteroids. Patients should also be monitored for infusion-related reactions. Other common side effects include headache and flu-like symptoms.

Patients treated with Hemgenix will be followed up for 15 years, to monitor the long-term efficacy and safety of this gene therapy.

Hemgenix was supported through EMA's PRIority MEdicines (PRIME) scheme, which provides early and enhanced scientific and regulatory support to medicines that have a particular potential to address patients' unmet medical needs.

In its overall assessment of the available data, the Committee for Advanced Therapies (CAT), EMA's expert committee for cell- and gene-based medicines, found that the benefits of Hemgenix outweighed the possible risks in patients with haemophilia B. The CHMP, EMA’s human medicines committee, agreed with the CAT’s assessment and positive opinion, and recommended approval of this medicine.

The opinion adopted by the CHMP is an intermediary step on Hemgenix’s path to patient access. The opinion will now be sent to the European Commission for the adoption of a decision on an EU-wide marketing authorisation. Once a marketing authorisation has been granted, decisions about price and reimbursement will take place at the level of each Member State, taking into account the potential role or use of this medicine in the context of the national health system of that country.

  • The applicant for Hemgenix is CSL Behring GmbH.
  • Hemgenix was designated as an orphan medicinal product on 21 March 2018. Following this positive CHMP opinion, the Committee for Orphan Medicinal Products (COMP) will assess whether the orphan designation should be maintained.
  • Hemgenix was granted eligibility to PRIME on 21 April 2017 for the treatment of severe haemophilia B.