Etranacogene dezaparvovec

KING OF PRUSSIA, PA, USA I February 7, 2025 I Global biotechnology leader CSL (ASX:CSL; USOTC:CSLLY) today announced the four-year results from the pivotal HOPE-B study confirming the long-term durability and safety of a one-time infusion of HEMGENIX ® (etranacogene dezaparvovec-drlb) for adults living with hemophilia B. In an oral presentation at the 18th Annual Congress of the European Association for Haemophilia and Allied Disorders (EAHAD), data showed that through four years, HEMGENIX continues to deliver elevated and sustained factor IX activity levels, can offer long-term and greater bleed protection compared to prophylactic treatment, can eliminate the need for routine factor IX prophylaxis, and maintains a favorable safety profile. Approved in 2022 by the U.S. Food and Drug Administration (FDA), HEMGENIX is the first gene therapy 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. It is also the only approved gene therapy for hemophilia B that can treat adult patients with and without AAV5 neutralizing antibodies thereby providing the potential for a greater number of eligible patients to be treated. “Hemophilia B can cause spontaneous bleeds into the joints, resulting in extreme pain and progressive, arthritis-like damage, which can lead to permanent physical debility,” said Steven Pipe, MD, Professor of Pediatrics and Pathology, Laurence A. Boxer Research Professor of Pediatrics and Communicable Diseases, Pediatric Medical Director, Hemophilia and Coagulation Disorders Program Director, Special Coagulation Laboratory University of Michigan. “These results underscore the ability of HEMGENIX to offer long-term bleed protection with a one-time treatment, resulting in dramatic decreases in all annual bleed rates, including joint bleeds, and sustained independence from regular prophylactic infusions.” In the Phase III, open-label, single-dose, single-arm HOPE-B trial, 54 adult male participants with severe or moderately severe hemophilia B, with or without preexisting AAV5 neutralizing antibodies, were infused with a single dose of HEMGENIX. Of the 54 participants who received HEMGENIX, 51 completed four years of follow-up. HEMGENIX produced mean factor IX levels of 41.5 IU/dL (n=50) at year one, 36.7 IU/dL (n=50) at year two, 38.6 IU/dL (n=48) at year three and 37.4 IU/dL (n=47) at year four post-infusion. In addition, mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately 90% from lead-in (4.16, n=54) as compared to year four (0.40, n=51). Furthermore, joint bleeds were reduced from a mean ABR of 2.34 at lead-in to 0.09 during year four. In year four, 94% of patients remained free of continuous prophylaxis treatment. No patients returned to continuous prophylaxis between year three and year four. There were no serious adverse events related to treatment with HEMGENIX. HEMGENIX was generally well-tolerated, with a total of 96 treatment-related adverse events (AEs), 92 (96%) of which occurred in the first six months post-treatment. The most common adverse events were an increase in alanine transaminase (ALT), for which nine (16.7%) participants received supportive care with reactive corticosteroids for a mean duration of 81.4 days (standard deviation: 28.6; range: 51-130 days). “These data continue to instill confidence in the clinical benefits of HEMGENIX, highlighting the remarkable impact of this one-time treatment to reduce the frequency of bleeds in people with hemophilia B and improve quality of life by alleviating the burden of ongoing factor IX prophylactic treatment,” said Andres Brainsky, Vice President R&D Hematology at CSL. “CSL is committed to continuing to provide ongoing data analyses of HEMGENIX, ensuring that healthcare providers and patients have the necessary information to make informed decisions about treatment options. We are proud to continue to provide life-changing treatment options to the hemophilia community.” 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. Additionally, CSL established a post-marketing registry, which will be informative to all stakeholders and will generate additional evidence on the long-term safety, efficacy, and durability of gene therapy. HEMGENIX has also been granted conditional marketing authorization by the European Commission (EC) for the European Union and European Economic Area, the UK’s Medicines and Healthcare products Regulatory Agency (MHRA), as well as authorization by Health Canada, Switzerland’s Swissmedic and provisional approval by Australia’s Therapeutic Goods Administration (TGA). For more information on HEMGENIX, please visit www.Hemgenix.com . 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 at least the six-month lead-in period, patients received a single intravenous administration of HEMGENIX at a 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 51 patients completing at least four years 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 sponsor company. 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. 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. Treatments for moderate to severe hemophilia B typically include life-long prophylactic infusions of factor IX to temporarily replace or supplement low levels of the blood-clotting factor. About HEMGENIX ® 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. Important Safety Information (ISI) What is HEMGENIX ® ? HEMGENIX ® , etranacogene dezaparvovec-drlb, is a one-time gene therapy for the treatment of adults with hemophilia B who: HEMGENIX is administered as a single intravenous infusion and can be administered only once. What medical testing can I expect to be given before and after administration of HEMGENIX? To determine your eligibility to receive HEMGENIX, you will be tested for Factor IX inhibitors. If this test result is positive, a retest will be performed 2 weeks later. If both tests are positive for Factor IX inhibitors, your doctor will not administer HEMGENIX to you. If, after administration of HEMGENIX, increased Factor IX activity is not achieved, or bleeding is not controlled, a post-dose test for Factor IX inhibitors will be performed. HEMGENIX may lead to elevations of liver enzymes in the blood; therefore, ultrasound and other testing will be performed to check on liver health before HEMGENIX can be administered. Following administration of HEMGENIX, your doctor will monitor your liver enzyme levels weekly for at least 3 months. If you have preexisting risk factors for liver cancer, regular liver health testing will continue for 5 years post-administration. Treatment for elevated liver enzymes could include corticosteroids. What were the most common side effects of HEMGENIX in clinical trials? 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. These are not the only side effects possible. Tell your healthcare provider about any side effect you may experience. What should I watch for during infusion with HEMGENIX? Your doctor will monitor you for infusion-related reactions during administration of HEMGENIX, as well as for at least 3 hours after the infusion is complete. Symptoms may include chest tightness, headaches, abdominal pain, lightheadedness, flu-like symptoms, shivering, flushing, rash, and elevated blood pressure. If an infusion-related reaction occurs, the doctor may slow or stop the HEMGENIX infusion, resuming at a lower infusion rate once symptoms resolve. What should I avoid after receiving HEMGENIX? Small amounts of HEMGENIX may be present in your blood, semen, and other excreted/secreted materials, and it is not known how long this continues. You should not donate blood, organs, tissues, or cells for transplantation after receiving HEMGENIX. Please see full prescribing information for HEMGENIX. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch , or call 1-800-FDA-1088. You can also report side effects to CSL Behring’s Pharmacovigilance Department at 1-866-915-6958. About CSL CSL (ASX:CSL; USOTC:CSLLY) is a global biotechnology company with a dynamic portfolio of lifesaving medicines, including those that treat haemophilia and immune deficiencies, vaccines to prevent influenza, and therapies in iron deficiency 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 32,000 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 CSL.com/Vita and follow us on Twitter.com/CSL . For more information about CSL, visit CSL.com. SOURCE: CSL Behring

CSL Behring is deprioritising its ex vivo lentiviral-based gene therapy platform and closing its hub for cell and gene therapy R&D in Pasadena, California as it explores other gene therapy approaches, a company spokesperson confirmed to FirstWord on Monday.The closure, set for the end of January 2025, comes as CSL's sole marketed gene therapy Hemgenix (etranacogene dezaparvovec-drlb) continues to face commercial hurdles.The spokesperson said CSL will consolidate its cell and gene therapy R&D operations in Waltham, Massachusetts, as part of a broader strategic evaluation of its R&D footprint. They didn't specify how many jobs would be affected, but said approximately 30 employees, primarily in Pasadena, will be leaving the company, though some staff have accepted relocation offers to the Waltham facility.CSL acquired the Pasadena site through its purchase of Calimmune in 2017 for an upfront payment of $91 million.The pivot comes amid industry scepticism about the commercial viability of certain gene therapy approaches. Recent expert feedback compiled by FirstWord indicates that while Hemgenix, which uses an in vivo method of gene transfer, has demonstrated clinical efficacy in haemophilia B, the therapy faces substantial financial and logistical barriers to widespread adoption, with physicians awaiting longer-term durability and safety data. See – Spotlight On: KOLs find a new balance in haemophilia B."This strategic shift will enable us to focus our resources on areas showing the most promise while enabling our teams working on the leading edge of genetic medicines — such as mRNA and gene therapy — to work closely together," the spokesperson said, adding that the company sees opportunities to capitalise on "strategic and technical convergence" with its self-amplifying mRNA capabilities.The closure of the Pasadena site, which CSL acquired along with Calimmune's Select+ and Cytegrity platforms for the development of ex vivo haematopoietic stem cell gene therapy, marks a departure from the company's initial gene therapy strategy. When CSL purchased Calimmune, then-CEO Paul Perreault had highlighted the acquisition as an "important step" in executing the company's strategy for sustainable growth, particularly in addressing commercialisation challenges in stem cell therapy.