• Data follow the historic approval of the first gene therapy for hemophilia B, which reduces the rate of annual bleeds, reduces or eliminates the need for prophylactic therapy and generates elevated and sustained factor IX levels for years after a one-time infusion
  • 18-month data support the efficacy and safety of HEMGENIX® and the ongoing benefit of this treatment
  • HEMGENIX® is approved for adults with hemophilia B in the United States, European Union and European Economic Area

CSL today announced the publication in the New England Journal of Medicine (NEJM) (Vol. 388 No. 8) results from the pivotal HOPE-B clinical study evaluating the efficacy, durability and safety of HEMGENIX® (etranacogene dezaparvovec-drlb). HEMGENIX® is the first and only gene therapy approved for the treatment of adults with hemophilia B who currently use factor IX prophylaxis therapy, or have current or historical life-threatening bleeding, or have repeated, serious spontaneous bleeding episodes.

Results from the HOPE-B trial, the largest gene therapy study in hemophilia B to date, were considered by the authors to demonstrate that HEMGENIX® is superior to routine factor IX prophylaxis in Annualized Bleeding Rate (ABR), 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 3 and maintained over 18 months. There were no serious treatment-related adverse events.

Notably, the results published in NEJM show 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. Further, the authors found 96.3% of patients discontinued factor IX prophylaxis from day 21 through month 18 post-treatment (the discontinuation rate in the approved U.S. HEMGENIX® product label is 94%). Annualized factor IX infusions also significantly decreased from 72.5 infusions per participant during lead-in period (95% CI: 63.6, 82.7) to 2.5 infusions (95% CI: 0.92, 6.96) post-treatment.

In clinical trials for HEMGENIX®, the most common side effects reported in more than 5% of patients were liver enzyme elevations, headache, elevated levels of a certain blood enzyme, flu-like symptoms, infusion-related reactions, fatigue, nausea and feeling unwell.

“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, but also that gene therapy may reduce the burden of care and improve quality of life for people living with this life-long condition,” said Dr. Steven Pipe, Professor and the Laurence A. Boxer Research Professor of Pediatrics and Professor of Pathology at the University of Michigan and lead investigator of the HOPE-B study. “HOPE-B was also the first and only phase 3 study to demonstrate efficacy of a gene therapy for hemophilia B in individuals with circulating neutralizing antibodies that have the potential to interfere with the effects of treatment. Results from HOPE-B suggest that HEMGENIX® may be effective in a broad range of hemophilia B patients, regardless of prior exposure to common adeno-associated viruses.”

The multi-year clinical development of HEMGENIX® was led by uniQure (Nasdaq: QURE) and sponsorship of the clinical trials transitioned to CSL after it licensed global rights to commercialize the treatment. HEMGENIX® was approved in November 2022 by the U.S. Food and Drug Administration (FDA), and in February 2023 by the European Commission (EC) for the European Union and European Economic Area.

“We are proud to showcase the HOPE-B trial data in such a prestigious publication,” said Brahm Goldstein, MD, Vice President, Research and Development, Hematology at CSL. “These results underscore the benefits of this novel approach and reinforce that those treated with HEMGENIX® will likely achieve durable factor IX activity levels and remain free of prophylactic factor IX replacement for years following a single administration. CSL remains steadfast in our commitment to deliver on our promise of innovation for people living with rare bleeding disorders.”

About Hemophilia B

Hemophilia B is a life-threatening rare disease. People with the condition are particularly vulnerable to bleeds in their joints, muscles, and internal organs, leading to pain, swelling, and joint damage. Current treatments for moderate to severe hemophilia B include life-long prophylactic infusions of factor IX to temporarily replace or supplement low levels of the blood-clotting factor.


HEMGENIX® is a gene therapy that reduces the rate of abnormal bleeding in eligible people with hemophilia B by enabling the body to continuously produce factor IX, the deficient protein in hemophilia B. It uses AAV5, a non-infectious viral vector, called an adeno-associated virus (AAV). The AAV5 vector carries the Padua gene variant of Factor IX (FIX-Padua) to the target cells in the liver, generating factor IX proteins that are 5x-8x more active than normal. These genetic instructions remain in the target cells, but generally do not become a part of a person’s own DNA. Once delivered, the new genetic instructions allow the cellular machinery to produce stable levels of factor IX.

About the Pivotal HOPE-B Trial

The pivotal Phase III HOPE-B trial is an ongoing, multinational, open-label, single-arm study to evaluate the safety and efficacy of HEMGENIX®. Fifty-four adult hemophilia B patients classified as having moderately severe to severe hemophilia B and requiring prophylactic factor IX replacement therapy were enrolled in a prospective, six-month or longer observational period during which time they continued to use their current standard of care therapy to establish a baseline Annual Bleeding Rate (ABR). After the six-month lead-in period, patients received a single intravenous administration of HEMGENIX® at the 2×10^13 gc/kg dose. Patients were not excluded from the trial based on pre-existing neutralizing antibodies (NAbs) to AAV5.

A total of 54 patients received a single dose of HEMGENIX® in the pivotal trial, with 53 patients completing at least 18 months of follow-up. The primary endpoint in the pivotal HOPE-B study was ABR 52 weeks after achievement of stable factor IX expression (months 7 to 18) compared with the six-month lead-in period. For this endpoint, ABR was measured from month seven to month 18 after infusion, ensuring the observation period represented a steady-state factor IX transgene expression. Secondary endpoints included assessment of factor IX activity.

No serious treatment-related adverse reactions were reported. One death resulting from urosepsis and cardiogenic shock in a 77-year-old patient at 65 weeks following dosing was considered unrelated to treatment by investigators and the company sponsor. A serious adverse event of hepatocellular carcinoma was determined to be unrelated to treatment with HEMGENIX® by independent molecular tumor characterization and vector integration analysis. No inhibitors to factor IX were reported.

Long-term 24-month data presented at the 54th American Society of Hematology (ASH) 2022 Annual Meeting and Exposition and at The European Association for Haemophilia and Allied Disorders (EAHAD) 2023 Annual Meeting continue to reinforce the potential long-lasting efficacy and safety of HEMGENIX® and the ongoing benefit of this treatment for people living with hemophilia B.

From PR News: https://www.prnewswire.com/news-releases/csls-hope-b-data-published-in-the-new-england-journal-of-medicine-demonstrating-efficacy-and-durability-of-hemgenix-etranacogene-dezaparvovec-drlb-301753751.html

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