Hemgenix lowers bleeding rates, replacement therapy use

Findings were from 52 hemophilia B patients who participated in HOPE-B study

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Bleeding rates and the use of replacement therapies among men with severe or moderately severe hemophilia B remain low at least three years after a single dose of the approved gene therapy Hemgenix (etranacogene dezaparvovec).

That’s according to updated data from the Phase 3 HOPE-B clinical trial (NCT03569891) shared last week at the 65th American Society of Hematology (ASH) Annual Meeting and Exposition in a presentation titled “Long-Term Bleeding Protection, Sustained FIX Activity, Reduction of FIX Consumption and Safety of Hemophilia B Gene Therapy: Results from the HOPE-B Trial 3 Years after Administration of a Single Dose of Etranacogene Dezaparvovec in Adult Patients with Severe or Moderately Severe Hemophilia B.”

“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,” said Steven Pascoe, MD, chief medical officer at CSL Behring, which markets the therapy, in a company press release. “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.”

Hemophilia B is caused by mutations in the gene that provides instructions to make the clotting protein factor IX (FIX). Hemgenix is designed to deliver a healthy, functioning version of the gene to liver cells, the main producer of clotting factors. Originally developed by uniQure and later licensed to CSL Behring, Hemgenix is expected to promote a working version of FIX and restore clotting ability. It’s approved in the U.S. and Canada to treat certain adults with hemophilia B. It’s also conditionally approved in the European Union and the U.K.

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Gene therapy for hemophilia A reduces bleeding in clinical trial

Early results of Hemgenix

The approvals were based largely on data from the Phase 3 HOPE-B study, which is assessing the five-year safety and effectiveness of a single dose of Hemgenix in 54 men with severe or moderately severe hemophilia.

Top-line results, covering up to 1.5 years of follow-up, indicate Hemgenix was generally safe and significantly increased FIX activity — to a mean of 36.9% of normal — and reduced bleeding rates. Clotting factor activity between 5% and 40% of normal is generally considered mild hemophilia, and before gene therapy, all HOPE-B participants had FIX activity at 2% or normal or lower.

These benefits were sustained for two years, with most men being able to stop using routine prophylactic (preventive) FIX replacement therapy.

The new findings concerned data from 52 patients in HOPE-B who completed at least three years of follow-up. Three years post-dosing, the average FIX activity was at 38.6% of normal, results showed.

Not counting the first six months after dosing when the gene therapy was taking effect, the mean bleeding rate over three years was 1.52 bleeds a year compared with 4.17 bleeds a year before gene therapy. This reflected a significant drop — by 64%.

Reduced use of replacement therapy

Hemgenix also let patients stop taking prophylactic FIX replacement therapies. After three years, 94% remained free from continuous prophylaxis, and 75% received no FIX therapies whatsoever in the third year post-treatment. Total consumption of FIX products decreased by 96%.

The long-term data didn’t reveal any notable new safety concerns. Virtually all the side effects associated with Hemgenix occurred in the first few months after it was administered.

The findings show Hemgenix provides “superior bleeding protection compared to FIX prophylaxis … with a favorable safety profile over [three] years post-administration,” the researchers wrote in the presentation’s abstract.

“The long-term follow-up data from the HOPE-B study reinforces that a one-time treatment with Hemgenix can produce elevated and sustained factor IX levels and reduce the rate of annual bleeds for years in people living with hemophilia B,” said Steven Pipe, MD, the trial’s principal investigator at the University of Michigan. “Most importantly, the data show that nearly all the Phase [3] trial participants three years post-treatment with Hemgenix have remained free from the need for regular prophylactic infusions, which is groundbreaking for the hemophilia B community.”

CSL “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.