Roche’s Hemlibra every four weeks controlled bleeds in phase III study in haemophilia A

• Less frequent administration of Hemlibra demonstrated clinically meaningful bleed control

Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced positive interim results from the phase III HAVEN 4 study evaluating Hemlibra® (emicizumab) prophylaxis dosed once every four weeks in adults and adolescents (12 years of age or older) with haemophilia A with and without inhibitors to factor VIII. At this interim analysis after a median of 17 weeks of treatment, Hemlibra prophylaxis showed a clinically meaningful control of bleeding. These results are consistent with previous studies of Hemlibra dosed once weekly or every two weeks, including the pivotal studies in haemophilia A with inhibitors, HAVEN 1 in adults and adolescents and HAVEN 2 in children, as well as the phase III HAVEN 3 study in adults and adolescents with haemophilia A without inhibitors. The most common adverse events with Hemlibra were injection site reactions, with no new safety signals observed. No thrombotic microangiopathy or thrombotic events occurred in this study.

“Current treatment regimens for haemophilia A can require frequent intravenous infusions. We are encouraged that Hemlibra prophylaxis administered by injection under the skin once every four weeks showed clinically meaningful bleed control in people with haemophilia A,” said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. “Together with the findings from other phase III studies, these interim results support the potential for Hemlibra to be dosed at different schedules, allowing patients to choose the option that’s right for them.”

Data from the HAVEN 4 study will be presented at an upcoming medical meeting and submitted to health authorities around the world for approval consideration. These results add to the growing body of evidence supporting that Hemlibra may benefit all people with haemophilia A regardless of inhibitor status, while providing flexible and less burdensome administration options.

About HAVEN 4 (NCT03020160)

HAVEN 4 is a single-arm, multicentre, open-label, phase III study evaluating the efficacy, safety and pharmacokinetics (PK) of subcutaneous administration of Hemlibra dosed every four weeks. The study included 48 patients (12 years of age or older) with haemophilia A with or without inhibitors to factor VIII who were previously treated with either factor VIII or bypassing agents, on-demand or as prophylaxis. The study was conducted in two parts: a PK run-in; and an expansion cohort. All patients in the PK run-in (n=7) were previously treated on-demand, and received subcutaneous Hemlibra at 6 mg/kg to fully characterize the PK profile after a single dose during four weeks, followed by 6 mg/kg every four weeks for at least 24 weeks. Patients in the expansion cohort (n= 41) received subcutaneous Hemlibra prophylaxis at 3 mg/kg/wk for four weeks, followed by 6 mg/kg every four weeks for at least 24 weeks. Episodic treatment of breakthrough bleeds with factor VIII therapy or bypassing agents, depending on a patient’s inhibitor status, was allowed per study protocol.

About Hemlibra (emicizumab)

Hemlibra is a bispecific factor IXa- and factor X-directed antibody. It is designed to bring together factor IXa and factor X, proteins required to activate the natural coagulation cascade and restore the blood clotting process for haemophilia A patients. Hemlibra is a prophylactic (preventative) treatment that can be administered by an injection of a ready-to-use solution under the skin (subcutaneously). The clinical development programme is assessing the safety and efficacy of Hemlibra and its potential to help overcome current clinical challenges: the short-lasting effects of existing treatments, the development of factor VIII inhibitors and the need for frequent venous access. Hemlibra was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche and Genentech. It is marketed in the United States as Hemlibra (emicizumab-kxwh) for patients with factor VIII inhibitors, with kxwh as the suffix designated in compliance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the US Food and Drug Administration.

About haemophilia A 

Haemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Haemophilia A affects around 320,000 people worldwide,^1,2  
approximately 50-60% of whom have a severe form of the disorder.³ People with haemophilia A either lack or do not have enough of a clotting protein called factor VIII. In a healthy person, when a bleed occurs, factor VIII brings together the clotting factors IXa and X, which is a critical step in the formation of a blood clot to help stop bleeding. 

Depending on the severity of their disorder, people with haemophilia A can bleed frequently, especially into their joints or muscles.¹ These bleeds can present a significant health concern as they often cause pain and can lead to chronic swelling, deformity, reduced mobility, and long-term joint damage.⁴ In addition to impacting a person’s quality of life,⁵ these bleeds can be life threatening if they go into vital organs, such as the brain.^6,7

About Roche in haematology

For more than 20 years, Roche has been developing medicines that redefine treatment in haematology. Today, we are investing more than ever in our effort to bring innovative treatment options to people with diseases of the blood. In addition to approved medicines MabThera®/Rituxan® (rituximab), Gazyva®/Gazyvaro® (obinutuzumab), and Venclexta™/Venclyxto™ (venetoclax) in collaboration with AbbVie, Roche’s pipeline of investigational haematology medicines includes Tecentriq® (atezolizumab), an anti-CD79b antibody drug conjugate (polatuzumab vedotin/RG7596) and a small molecule antagonist of MDM2 (idasanutlin/RG7388). Roche’s dedication to developing novel molecules in haematology expands beyond malignancy, with the development of Hemlibra® (emicizumab), a bispecific monoclonal antibody for the treatment of haemophilia A.

About Roche

Roche is a global pioneer in pharmaceuticals and diagnostics focused on advancing science to improve people’s lives. The combined strengths of pharmaceuticals and diagnostics under one roof have made Roche the leader in personalised healthcare – a strategy that aims to fit the right treatment to each patient in the best way possible.

Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and diseases of the central nervous system. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management.
Founded in 1896, Roche continues to search for better ways to prevent, diagnose and treat diseases and make a sustainable contribution to society. The company also aims to improve patient access to medical innovations by working with all relevant stakeholders. Thirty medicines developed by Roche are included in the World Health Organization Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and cancer medicines. Roche has been recognised as the Group Leader in sustainability within the Pharmaceuticals, Biotechnology & Life Sciences Industry nine years in a row by the Dow Jones Sustainability Indices (DJSI).

The Roche Group, headquartered in Basel, Switzerland, is active in over 100 countries and in 2016 employed more than 94,000 people worldwide. In 2016, Roche invested CHF 9.9 billion in R&D and posted sales of CHF 50.6 billion. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan. For more information, please visit www.roche.com.

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References

1. WFH. Guidelines for the management of hemophilia. [Internet; cited 2012]. Available from: http://www1.wfh.org/publications/files/pdf-1472.pdf
2. Berntorp E, Shapiro AD. Modern haemophilia care. The Lancet 2012; 370:1447-1456.
3. Marder VJ, et al. Hemostasis and Thrombosis. Basic Principles and Clinical Practice. 6th Edition, 2013. Milwakee, Wisconsin. Lippincott Williams and Wilkin.
4. Franchini M, Mannucci PM. Hemophilia A in the third millennium. Blood Rev 2013; 179-84.
5. Flood, E et al. Illustrating the impact of mild/moderate and severe haemophilia on health-related quality of life: hypothesised conceptual models. European Journal of Haematology 2014; 93: Suppl. 75, 9–18.
6. Young G. New challenges in hemophilia: long-term outcomes and complications. Hematology Am Soc Hematol Educ Program 2012. 2012; 362–8.
7. Zanon E, Iorio A, Rocino A, et al. Intracranial haemorrhage in the Italian population of haemophilia patients with and without inhibitors. Haemophilia 2012; 18: 39–45.