New gene therapy reduces bleeding rates for hemophilia B patients
Study conducted in China, where BBM-H901 was recently approved
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BBM-H901 gene therapy significantly reduces bleeding rates in hemophilia B patients.
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It delivers a gene encoding functional factor XI via a one-time infusion.
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The therapy is approved in China and shows positive efficacy and safety.
BBM-H901 (dalnacogene ponparvovec), a gene therapy that’s approved in China for adults with moderate to severe hemophilia B, was shown to significantly reduce bleeding rates among hemophilia B patients in clinical trials, a new study shows.
Hemophilia B is a genetic disorder caused by mutations in the gene that encodes the clotting protein factor IX (FIX). A lack of FIX activity means blood cannot clot correctly, resulting in symptoms such as easy and prolonged bleeding. Standard treatment involves replacement therapy, where a functional version of the FIX protein is regularly administered to control or prevent bleeding.
The overarching goal of gene therapy for hemophilia B is to deliver a gene encoding functional FIX to the body’s cells, allowing the body to produce its own supply of functional FIX protein and help control bleeding. BBM-H901 specifically aims to deliver a gene encoding FIX with the Padua variant, a mutation that naturally occurs in some individuals and causes the FIX protein to be more active.
BBM-H901 administered by one-time infusion into bloodstream
Earlier this year, BBM-H901 became the first hemophilia B gene therapy to be approved in China. The therapy, administered by a one-time infusion into the bloodstream, was developed by Belief Biomed (BBM) and is being commercialized by Takeda China.
A Phase 1 clinical trial (NCT04135300) tested BBM-H901 in 10 men with hemophilia B, and the results demonstrated that the therapy stably increased FIX levels, with most patients able to discontinue FIX replacement therapy while experiencing no bleeding episodes.
Following the Phase 1 study, researchers launched a Phase 1/2 study to further test the therapy. The Phase 1/2 study originally aimed to test multiple doses of BBM-H901, but results from the first six patients — all of whom got the same dose used in the original Phase 1 study — showed acceptable safety and good efficacy, with all able to discontinue FIX replacement while still experiencing no bleeds over a year of follow-up.
Since the early data were promising, the committee overseeing the trial decided to scrap plans for testing higher doses and instead move the original dose directly into further testing in a Phase 3 clinical trial (NCT05203679). A team including scientists at BBM reported results from the Phase 1/2 and Phase 3 trials in the study, “Factor IX-Padua AAV gene therapy in hemophilia B: phases 1/2 and 3 trials,” which was published in Nature Medicine.
[BBM-H901] “achieves positive efficacy and safety in Chinese patients with hemophilia B, supplementing global data for FIX-Padua gene therapy.
In the Phase 3 trial, 26 people with moderate-to-severe hemophilia B received a one-time treatment with BBM-H901. Results showed the gene therapy led to a rapid increase in FIX activity as designed. After a year of follow-up, average FIX levels were close to the lower end of what’s considered normal for people without hemophilia.
Phase 3 data also showed a sharp decline in bleeding rates following gene therapy. Before BBM-H901 treatment, patients were averaging nearly nine bleeds per year. In the year following gene therapy, the average bleeding rate decreased to less than one per year, with all but five patients reporting no bleeds at all, and all but four experiencing no need for FIX replacement. While a few participants still experienced occasional joint bleeds, none had any target joints, defined as specific joints with frequent, recurring bleeding, one year after treatment.
Safety data showed no severe side effects of BBM-H901. The most common side effects related to the gene therapy were increases in markers of liver damage. The researchers stated that, overall, the trial data compare favorably with data from clinical trials of Hemgenix (etranacogene dezaparvovec-drlb), a gene therapy for hemophilia B marketed by CSL Behring and approved in the U.S., Canada, and Europe.
The scientists concluded that BBM-H901 “achieves positive efficacy and safety in Chinese patients with hemophilia B, supplementing global data for FIX-Padua gene therapy.” They added that patients in these trials are continuing to be monitored for long-term outcomes.
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