Female nurse collects blood from senior patient for testing at hospital
Credit: Yoshiyoshi Hirokawa/Gatty Images

The potential transformation of hemophilia treatment through gene therapy was reaffirmed last week when results from the pivotal trial of CSL’s Hemgenix (etranacogene dezaparvovec-drlb) for hemophilia B appeared in the New England Journal of Medicine (NEJM). The same issue featured a positive report on two-year follow up of a trial for Roctavian (valoctocogene roxaparvovec), a gene therapy from BioMarin for hemophilia A.

“The results published in NEJM add to the established body of evidence demonstrating the long-term efficacy and safety of Hemgenix and confirm that this innovative new medicine not only restores blood clotting factor to near normal levels and significantly reduces factor use,” said Steven Pipe, Professor of Pathology at the University of Michigan and lead investigator of the HOPE-B study.

Results for Roctavian, meanwhile, showed the durability and safety of the treatment for at least two years. After just over 100 weeks, among a total of 132 participants. The mean annualized treated bleeding rate (ABR) decreased by 84.5% from baseline (P<0.001) among the participants.

Hemophilia is an inherited clotting disorder that primarily affects men. The two most common types are hemophilia A, which is due to a lack of clotting factor VIII and hemophilia B, which is due to a lack of clotting factor IX. Either can lead to spontaneous bleeding into muscles, organs, and joints as well as prolonged bleeding following injuries or surgery. It’s estimated that that more than 1,125,000 men around the world have hemophilia, 418,000 of those have a severe version.

There is a lot of activity around developing new hemophilia treatments. Hemgenix is approved in the U.S. and Europe. Roctavian is approved for conditional use in the European Union.

In the Hemgenix trial, a total of 54 patients received a single dose of the treatment, with 53 patients completing at least 18 months of follow-up. Results showed the treatment is superior to routine factor IX prophylaxis, and demonstrated significant improvements in factor IX activity, factor IX therapy consumption, factor IX infusion rate, and spontaneous and joint bleeding ABR. Increased factor IX activity was also apparent from week three and maintained over 18 months. There were no serious treatment-related adverse events.

Notably, the ABR of spontaneous bleeding episodes and all joint bleeding episodes decreased by 71% (95% CI: 0.12, 0.71) and 78% (95% CI: 0.10, 0.46), respectively, from lead-in period to post-treatment.

Hemgenix’s development was led by uniQure. CSL licensed global rights to commercialize the treatment. The therapy works by enabling the body to continuously produce factor IX and uses the AAV5 vector carrying the Padua gene variant of Factor IX to target cells in the liver. BioMarin’s Roctavian also uses an AAV5 vector, but increases production of Factor VIII.

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