Global biotechnology leader CSL (ASX: CSL) today announced that Health Canada has authorized HEMGENIX® (etranacogene dezaparvovec), the first and only gene therapy for the treatment of hemophilia B. HEMGENIX is indicated for the treatment of adults with hemophilia B who require routine prophylaxis to prevent or reduce the frequency of bleeding episodes. There is no clinical experience of HEMGENIX use in patients with mild or moderate hemophilia B (FIX activity >2%).
The approval is based on results from the ongoing Phase III, open label, single-dose, single-arm, multi-center HOPE-B trial of 54 participants, the largest gene therapy trial in hemophilia B to date. Data from the pivotal trial show that people with hemophilia B treated with a single infusion of HEMGENIX demonstrated significant increases in mean FIX activity levels (as measured by one-stage assay) of 36.9% at 18-months, that were sustained at 36.7% at 24-months post-treatment, compared to the six-month lead in period. Seven to 18 months post-infusion, the mean ABR was reduced by 58% compared to the six-month lead-in period (4.13 to 1.73). Following infusion of HEMGENIX, 96% of patients (52 out of 54) discontinued use of prophylaxis and remained free of previous continuous routine prophylaxis therapy. Of the adverse events reported based on phase 2b and phase 3 trial (Hope-B), most frequently reported adverse drug reactions were ALT elevations, headache, influenza-like illness and AST elevations.
“This approval continues to demonstrate CSL’s promise to pursue, develop and deliver new innovative treatment options that meet the needs of the rare disease community,” said Dr. Bill Mezzanotte, Head of Research and Development, CSL. “We believe HEMGENIX has the potential to change the treatment paradigm for people living with hemophilia B and the healthcare professionals who treat them, as it addresses the cause of the condition – faulty factor IX gene expression.”
Hemophilia B is a rare, lifelong bleeding disorder caused by a single gene defect, resulting in insufficient production of factor IX, a protein primarily produced by the liver that helps the blood to properly clot. Treatments for hemophilia B include prophylactic infusions of factor IX replacement therapy to temporarily replace or supplement low levels of blood-clotting factor and, while these therapies are effective, those with hemophilia B must adhere to strict, lifelong infusion schedules. Those with hemophilia B may also still experience spontaneous bleeding episodes as well as limited mobility, joint damage, or severe pain as a result of the disease. HEMGENIX allows people living with hemophilia B to produce their own factor IX, which can lower the risk of bleeding.
“The approval of HEMGENIX in Canada marks an important milestone and we look forward to collaborating with the hemophilia B community to provide access to this innovative treatment option,” said Philippe Hebert, General Manager Canada, CSL Behring. “We are proud to add this treatment to our portfolio of coagulation therapies and look forward to patients benefiting from this therapy.”
HEMGENIX® was also approved by the U.S. Food and Drug Administration, and was granted conditional marketing authorization by the European Commission (EC) for the European Union and European Economic Area, and the United Kingdom's Medicines and Healthcare products Regulatory Agency (MHRA). 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.
About Hemophilia B
Hemophilia B is a life-threatening rare disease caused by a mutation on the F9 gene, resulting in low levels of functional clotting factor IX. 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 2x10^13 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 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.
Important Information for Canada
For more information and a complete risk/benefit profile, please refer to the Product Monograph available here.
CSL (ASX:CSL; USOTC:CSLLY) is a leading global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat hemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency, dialysis and nephrology. Since our start in 1916, we have been driven by our promise to save lives using the latest technologies. Today, CSL – including our three businesses, CSL Behring, CSL Seqirus and CSL Vifor – provides lifesaving products to patients in more than 100 countries and employs 30,000 people. Our unique combination of commercial strength, R&D focus and operational excellence enables us to identify, develop and deliver innovations so our patients can live life to the fullest. For inspiring stories about the promise of biotechnology, visit CSLBehring.com/Vita and follow us on Twitter.com/CSL.
For more information about CSL, visit www.CSL.com.
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