CSL Behring's Gene Therapy HEMGENIX® (etranacogene dezaparvovec-drlb) Four Years Post-Infusion Data Continue to Show Sustained Efficacy and Safety in Adults with Hemophilia B
CSL Behring announced four-year results from the pivotal HOPE-B study of HEMGENIX, their gene therapy for hemophilia B. The data demonstrates sustained efficacy and safety through four years post-treatment. Key findings include:
- 94% of patients remained free of continuous factor IX prophylaxis
- Mean factor IX activity levels maintained at 37% through four years
- Approximately 90% reduction in mean adjusted annualized bleeding rate from lead-in to year four
- Joint bleeds reduced from 2.34 to 0.09 mean ABR
The Phase III HOPE-B trial involved 54 adult male participants with severe or moderately severe hemophilia B. No serious adverse events related to HEMGENIX were reported, with 96% of treatment-related adverse events occurring in the first six months. HEMGENIX, approved by FDA in 2022, is the first gene therapy for hemophilia B that can treat patients with and without AAV5 neutralizing antibodies.
CSL Behring ha annunciato i risultati quadriennali dello studio principale HOPE-B su HEMGENIX, la loro terapia genica per l'emofilia B. I dati dimostrano un'efficacia e sicurezza sostenute nel corso di quattro anni dopo il trattamento. I principali risultati includono:
- Il 94% dei pazienti è rimasto privo di profilassi continua con fattore IX
- I livelli medi di attività del fattore IX sono stati mantenuti al 37% per quattro anni
- Riduzione di circa il 90% del tasso annuale medio di sanguinamento aggiustato dal periodo iniziale al quarto anno
- Emorragie articolari ridotte da 2,34 a 0,09 di ABR medio
Lo studio di Fase III HOPE-B ha coinvolto 54 partecipanti maschi adulti con emofilia B severa o moderatamente severa. Non sono stati segnalati eventi avversi gravi correlati a HEMGENIX, con il 96% degli eventi avversi legati al trattamento che si sono verificati nei primi sei mesi. HEMGENIX, approvato dalla FDA nel 2022, è la prima terapia genica per l'emofilia B in grado di trattare pazienti con e senza anticorpi neutralizzanti AAV5.
CSL Behring anunció los resultados de cuatro años del estudio pivotal HOPE-B sobre HEMGENIX, su terapia génica para la hemofilia B. Los datos demuestran una eficacia y seguridad sostenidas a lo largo de cuatro años post-tratamiento. Los hallazgos clave incluyen:
- El 94% de los pacientes permanecieron libres de profilaxis continua con factor IX
- Los niveles medios de actividad del factor IX se mantuvieron en un 37% durante cuatro años
- Reducción de aproximadamente el 90% en la tasa anualizada media de hemorragias ajustada desde el periodo inicial hasta el cuarto año
- Las hemorragias articulares se redujeron de 2,34 a 0,09 de ABR medio
El ensayo de Fase III HOPE-B involucró a 54 participantes masculinos adultos con hemofilia B severa o moderadamente severa. No se informaron eventos adversos graves relacionados con HEMGENIX, y el 96% de los eventos adversos relacionados con el tratamiento ocurrieron en los primeros seis meses. HEMGENIX, aprobado por la FDA en 2022, es la primera terapia génica para la hemofilia B que puede tratar a pacientes con y sin anticuerpos neutralizantes AAV5.
CSL Behring는 HEMGENIX에 대한 주요 연구 HOPE-B의 4년 결과를 발표했습니다. HEMGENIX는 그들의 혈우병 B 유전자 치료제입니다. 데이터는 치료 후 4년 동안 지속적인 효능과 안전성을 보여줍니다. 주요 발견 내용은 다음과 같습니다:
- 94%의 환자가 계속적인 IX 인자 예방 치료 없이 지냈습니다.
- 평균 IX 인자 활성 수준이 4년 동안 37%로 유지되었습니다.
- 첫 번째 기간에서 4년까지 평균 조정 연간 출혈율이 약 90% 감소했습니다.
- 관절 출혈이 평균 ABR에서 2.34에서 0.09로 감소했습니다.
3상 HOPE-B 시험에는 중증 또는 중간 중증 혈우병 B를 가진 성인 남성 54명이 참여했습니다. HEMGENIX와 관련된 심각한 부작용은 보고되지 않았으며, 치료 관련 부작용의 96%는 처음 6개월 동안 발생했습니다. HEMGENIX는 2022년에 FDA의 승인을 받았으며, AAV5 중화 항체가 있는 환자와 없는 환자 모두 치료할 수 있는 최초의 혈우병 B 유전자 치료제입니다.
CSL Behring a annoncé les résultats sur quatre ans de l'étude pivot HOPE-B concernant HEMGENIX, leur thérapie génique pour l'hémophilie B. Les données démontrent une efficacité et une sécurité soutenues sur quatre ans après le traitement. Les principaux résultats incluent:
- 94% des patients sont restés exempts de prophylaxie continue du facteur IX
- Les niveaux moyens d'activité du facteur IX se sont maintenus à 37% pendant quatre ans
- Réduction d'environ 90% du taux annuel moyen ajusté de saignement entre la période de référence et la quatrième année
- Les hémorragies articulaires réduites de 2,34 à 0,09 de ABR moyen
L'essai de Phase III HOPE-B a impliqué 54 participants masculins adultes atteints d'hémophilie B sévère ou modérément sévère. Aucun événement indésirable grave lié à HEMGENIX n'a été signalé, 96% des événements indésirables liés au traitement s'étant produits dans les six premiers mois. HEMGENIX, approuvé par la FDA en 2022, est la première thérapie génique pour l'hémophilie B capable de traiter des patients avec ou sans anticorps neutralisants AAV5.
CSL Behring hat die vierjährigen Ergebnisse der entscheidenden HOPE-B-Studie zu HEMGENIX, ihrer Gentherapie für Hämophilie B, bekannt gegeben. Die Daten zeigen eine nachhaltige Wirksamkeit und Sicherheit über vier Jahre nach der Behandlung hinweg. Zu den wichtigsten Ergebnissen gehören:
- 94% der Patienten blieben ohne kontinuierliche Faktor-IX-Prophylaxe
- Die mittleren Faktor-IX-Aktivitätswerte blieben über vier Jahre bei 37%
- Eine Reduzierung von etwa 90% der durchschnittlich justierten jährlichen Blutungsrate vom Ausgangswert bis zum vierten Jahr
- Gelenkblutungen reduzierten sich von 2,34 auf 0,09 durchschnittliche ABR
Die Phase-III-Studie HOPE-B umfasste 54 erwachsene männliche Teilnehmer mit schwerer oder mäßig schwerer Hämophilie B. Es wurden keine schwerwiegenden unerwünschten Ereignisse im Zusammenhang mit HEMGENIX berichtet, wobei 96% der behandlungsbedingten unerwünschten Ereignisse in den ersten sechs Monaten auftraten. HEMGENIX, das 2022 von der FDA zugelassen wurde, ist die erste Gentherapie für Hämophilie B, die Patienten mit und ohne AAV5-neutralisierende Antikörper behandeln kann.
- 94% of patients eliminated need for continuous prophylaxis treatment through year 4
- 90% reduction in annualized bleeding rate from baseline to year 4
- Sustained factor IX activity levels near normal (37.4%) through 4 years
- Significant reduction in joint bleeds from 2.34 to 0.09 mean ABR
- No serious adverse events related to treatment reported
- 96 treatment-related adverse events reported, with ALT increase being most common
- 9 participants (16.7%) required corticosteroid treatment for adverse events
Insights
The 4-year HOPE-B study results for HEMGENIX represent a significant milestone in gene therapy for hemophilia B. The data demonstrates remarkable durability with factor IX activity levels maintained at
The safety profile is particularly noteworthy in the context of gene therapies, where long-term safety concerns often present significant hurdles. The observation that
A important differentiator for HEMGENIX is its ability to treat patients with pre-existing AAV5 antibodies, expanding the eligible patient population compared to potential competitors. This feature, combined with the robust efficacy data, positions HEMGENIX favorably in the hemophilia B treatment landscape.
The establishment of a post-marketing registry demonstrates CSL's commitment to gathering real-world evidence, which will be important for broader adoption and potential label expansions. The global regulatory approvals across major markets (FDA, EC, MHRA, Health Canada, Swissmedic, TGA) provide multiple revenue streams and validate the therapy's potential.
From a healthcare economics perspective, the elimination of continuous prophylaxis in
- 94 percent of patients eliminated factor IX prophylaxis and remained free of continuous prophylaxis through four years post-treatment
- Mean factor IX activity levels were sustained at near normal levels of
37% through four years post-treatment, reinforcing the efficacy of HEMGENIX in the treatment of hemophilia B - Phase 3 HOPE-B data showed that a one-time treatment with HEMGENIX provided long-term bleed protection as mean adjusted annualized bleeding rate (ABR) for all bleeds was reduced by approximately
90% from lead-in as compared to year four
"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
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
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 (
"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
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 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 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:
- Currently use Factor IX prophylaxis therapy, or
- Have current or historical life-threatening bleeding, or
- Have repeated, serious spontaneous bleeding episodes.
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
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.
Media Contacts
Etanjalie Ayala, CSL Behring
Mobile: +1 610 297 1069
Email: etanjalie.ayala@cslbehring.com
Stephanie Fuchs, CSL Behring
Mobile: +49 151 58438860
Email: Stephanie.Fuchs@cslbehring.com
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SOURCE CSL Behring
FAQ
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