Hemgenix Gene Therapy Shows Long-Term Efficacy, Safety in Hemophilia B Patients

Men with severe or moderately severe hemophilia B continue to display low bleeding rates and very little use of replacement therapies for at least three years following a single dose of the approved gene therapy hemgenix (etranacogene dezaparvovec), according to results recently shared from a Phase 3 HOPE-B clinical trial.

Hemgenix is the first and only gene therapy approved by the FDA for the treatment of hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening bleeding, or have repeated, serious spontaneous bleeding episodes.

Hemgenix is the first and only gene therapy approved by the FDA for the treatment of hemophilia B who currently use factor IX prophylaxis therapy, have current or historical life-threatening bleeding, or have repeated, serious spontaneous bleeding episodes.

The gene therapy is a specialty drug made with the virus called AAV5. It carries a modified version of human FIX DNA and is designed to be used in the liver. Administration is through intravenous infusion, with the dosage measured at 2 x 10^13 particles per kilogram, according to the clinical trial data.

Conducted by researchers of global biotech leader, CSL, this trial is underway to examine the efficacy and safety of the drug.

In an open-label, single-dose, multi-center, multinational trial, 54 male participants within the United States and other countries with severe or moderately severe hemophilia B were monitored starting in 2018 with results last updates in December 2023. The study is expected to be completed by 2025.

Among the participants, 52 successfully completed the comprehensive three-year follow-up.

Data found that, hemgenix produced mean factor IX levels of 41.5 IU/dL at year one, 36.7 IU/dL at year two, and 38.6 IU/dL at year three post-treatment. Ninety-four percent of patients remained free from continuous prophylactic therapy.

The three-year data showed a 64% reduction in the mean annualized bleeding rate (ABR) for all bleeds was observed during months seven through 36 of the study (mean ABR 1.52 vs. 4.17 during the lead-in period; p=0.0004), aligning with the study's primary endpoint.

The FDA-approved prescribing information for the drug revealed a 54% reduction in ABR for all bleeds during months seven through 18.

Median bleeds per participant dropped from 2.0 in the lead-in period to a stable 0.0 throughout years one to three.

Overall, hemgenix displayed to be a safe drug with no serious adverse events linked to treatment.

Majority of adverse events (76%) were classified as mild, and 95% occurred within six months post-treatment.

The most common adverse events involved an increase in alanine transaminase (ALT), with nine participants (16.7%) receiving supportive care, including reactive corticosteroids for an average duration of 81.4 days (standard deviation: 28.6; range: 51-130 days).

This data was also presented in an oral presentation at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in early December this year.

Steven Pascoe, M.D., chief medical officer of CSL, said in a press release that “gene therapy is a novel treatment that addresses unmet needs in the hemophilia B community and the data presented at ASH continues to provide confidence in the clinical benefits of HEMGENIX.”

"As part of our commitment to the hemophilia B community, we will continue to follow the participants from the HOPE-B study as well as those who have been treated with HEMGENIX post FDA approval to generate additional evidence supporting the long-term safety, efficacy and durability of this one-time treatment,” Pascoe said. “We encourage healthcare professionals to continue to have open conversations with their patients about individual treatment goals and whether HEMGENIX may be an appropriate treatment option."