EMA has recommended granting a conditional marketing authorization in the European Union (EU) for Hemgenix (etranacogene dezaparvovec) for the treatment of severe and moderately severe hemophilia B in adults who do not have factor IX inhibitors. Haemophilia B is an inherited disorder characterized by an increased bleeding tendency due to a partial or complete deficiency of coagulation factor IX. The deficiency of factor IX is the result of mutations of the respective clotting factor gene. Prolonged bleeding episodes in patients with hemophilia B can lead to serious complications, such as bleeding into joints, muscles or internal organs, including the brain. Hemophilia B is a rare debilitating disease affecting approximately 1 in 20,000 to 50,000 live male newborns.

Medicines currently authorized to treat hemophilia 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 hemophilia B. It is delivered as a single infusion. Etranacogene dezaparvovec is based on a virus 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 starts 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 hemophilia 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 (annualized bleeding rate reduced from 4.19 to 1.51 bleedings per year after the infusion), achieves clinically relevant levels of factor IX activity, and minimizes 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, a common side effect due to immune reactions induced by these AAV-based gene therapies and characterized by an increase in the levels of liver 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.

Read the full text here.

References

  1. First gene therapy to treat haemophilia B – European Medicines Agency. (2022, December 16). European Medicines Agency. https://www.ema.europa.eu/en/news/first-gene-therapy-treat-haemophilia-b

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