For Most Patients, Factor Replacement Likely Unnecessary Up to 25 Years After Gene Therapy for Hemophilia B

After a single, full-dose infusion of the gene therapy etranacogene dezaparvovec, patients with hemophilia B would likely achieve durable factor IX activity levels and not require factor replacement therapies for up to 25.5 years, predictive analyses suggest. Researchers published the findings in the journal Current Medical Research and Opinion.

“Hemophilia B … is caused by a change or mutation to a gene, leading to lower-than-normal levels of a clotting factor, called factor IX. Standard treatment involves replacing missing factor IX through lifelong, regular treatment with factor replacement products,” explained researchers from CSL Behring, King of Prussia, Pennsylvania. “Etranacogene dezaparvovec is a gene therapy developed to replace the faulty gene and increase factor IX activity levels in the blood, thereby reducing bleeding, after one treatment.”

Although clinical trials have demonstrated factor IX activity level increases after etranacogene dezaparvovec treatment over observed study periods, long-term durability has not been established. To gauge the therapy’s long-term effect on factor IX activity, researchers used Bayesian and Frequentist linear mixed models to analyze 55 participants from Phase 2b and Phase 3 studies who responded to etranacogene dezaparvovec treatment.

According to the study, models predicted that no more than 10.91% of the participants would have unacceptable factor IX activity levels up to 25.5 years after etranacogene dezaparvovec infusion. In future patients with hemophilia B, models predicted that more than 80% would require no treatment with factor replacement products 25.5 years after etranacogene dezaparvovec infusion.

“Thus, based on the data observed, we predict that a single, full dose of etranacogene dezaparvovec will likely lead to durable factor IX expression for up to 25.5 years and prevent most people with hemophilia B from returning to prophylactic factor IX replacement products,” researchers reported.

Reference:
Shah J, Kim H, Sivamurthy K, Monahan PE, Fries M. Comprehensive analysis and prediction of long-term durability of factor IX activity following etranacogene dezaparvovec gene therapy in the treatment of hemophilia B. Curr Med Res Opin. 2023;39(2):227-237. doi:10.1080/03007995.2022.2133492