• Data include results from HAVEN 3 study in people with hemophilia A without factor VIII inhibitors and HAVEN 4 study in people with hemophilia A with or without factor VIII inhibitors;
• Ongoing HEMLIBRA clinical development program demonstrates commitment to advancing care for all people with hemophilia A.
Genentech, a member of the Roche Group, announced today that Phase III results for HEMLIBRA® (emicizumab-kxwh) will be presented for the first time during the World Federation of Hemophilia (WFH) 2018 World Congress (wfh.org) from May 20-24 in Glasgow, Scotland. The late-breaking presentations include positive results from the pivotal HAVEN 3 study of HEMLIBRA dosed every week or every two weeks in people with hemophilia A without factor VIII inhibitors and the pivotal HAVEN 4 study of HEMLIBRA dosed every four weeks in people with hemophilia A with or without factor VIII inhibitors. These data support the promising potential of HEMLIBRA for all people with hemophilia A.
“We look forward to sharing these new results from the HAVEN 3 and HAVEN 4 studies, which demonstrate the potential of HEMLIBRA to redefine treatment expectations for people with hemophilia A with and without inhibitors to factor VIII,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We will also be sharing real-world data that provides new insight into the impact of hemophilia A treatment on daily life, as part of our ongoing commitment to advancing management and care for the global hemophilia community.”
Data from the HAVEN 3 and HAVEN 4 studies will be presented for the first time in late-breaking oral presentations on Monday, May 21. The HAVEN 3 presentation will highlight new data on HEMLIBRA prophylaxis administered every week or every two weeks in people 12 years of age or older with hemophilia A without factor VIII inhibitors compared to no prophylaxis. The presentation will also include results from an intra-patient analysis comparing HEMLIBRA prophylaxis to prior treatment with factor VIII prophylaxis. The U.S. Food and Drug Administration (FDA) recently granted Breakthrough Therapy Designation for HEMLIBRA in people with hemophilia A without factor VIII inhibitors based on data from this study. The HAVEN 4 presentation will highlight primary data in people 12 years of age or older with hemophilia A with or without factor VIII inhibitors receiving HEMLIBRA prophylaxis every four weeks.
These presentations at WFH follow the announcement of positive top-line results from the HAVEN 3 study in November 2017 and positive top-line interim results from the HAVEN 4 study in December 2017. Data from both studies are being submitted to health authorities around the world for approval consideration.
Genentech will also present real-world data from a non-interventional study in adults with hemophilia A without factor VIII inhibitors and children with hemophilia A with factor VIII inhibitors. These data on health-related quality of life and health status will provide insights into challenges of living with and managing hemophilia A for patients and caregivers.
About HAVEN 3 (NCT02847637)
HAVEN 3 is a randomized, multicenter, open-label, Phase III study evaluating the efficacy, safety and pharmacokinetics of HEMLIBRA prophylaxis versus no prophylaxis (episodic/on-demand factor VIII treatment) in people with hemophilia A without factor VIII inhibitors. The study included 152 patients with hemophilia A (12 years of age or older) who were previously treated with factor VIII therapy either on-demand or for prophylaxis. Patients previously treated with on-demand factor VIII were randomized in a 2:2:1 fashion to receive subcutaneous HEMLIBRA prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (Arm A), subcutaneous HEMLIBRA prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks for at least 24 weeks (Arm B), or no prophylaxis (Arm C). Patients previously treated with factor VIII prophylaxis received subcutaneous HEMLIBRA prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 1.5 mg/kg/wk until the end of study (Arm D). Episodic treatment of breakthrough bleeds with factor VIII therapy was allowed per protocol.
About HAVEN 4 (NCT03020160)
HAVEN 4 is a single-arm, multicenter, 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 hemophilia A with or without factor VIII inhibitors 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 factor VIII inhibitor status, was allowed per study protocol.
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 hemophilia 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) once weekly. HEMLIBRA was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche and Genentech.
HEMLIBRA U.S. Indication
HEMLIBRA is a prescription medicine used for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors.
Important Safety Information
What is the most important safety information to know about HEMLIBRA?
HEMLIBRA increases the potential for blood to clot. Discontinue prophylactic use of bypassing agents the day before starting HEMLIBRA prophylaxis. Carefully follow the healthcare provider’s instructions regarding when to use an on-demand bypassing agent, and the dose and schedule one should use. Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving HEMLIBRA prophylaxis.
HEMLIBRA may cause the following serious side effects when used with aPCC (FEIBA®), including:
• Thrombotic microangiopathy (TMA). This is a condition involving blood clots and injury to small blood vessels that may cause harm to one’s kidneys, brain, and other organs. Patients should get medical help right away if they have any of the following signs or symptoms during or after treatment with HEMLIBRA:
- swelling of arms and legs
- yellowing of skin and eyes
- stomach (abdomen) or back pain
- nausea or vomiting
- feeling sick
- decreased urination
• Blood clots (thrombotic events). Blood clots may form in blood vessels in one’s arm, leg, lung or head. Patients should get medical help right away if they have any of these signs or symptoms of blood clots during or after treatment with HEMLIBRA:
- swelling in arms or legs
- pain or redness in the arms or legs
- shortness of breath
- chest pain or tightness
- fast heart rate
- cough up blood
- feel faint
- numbness in the face
- eye pain or swelling
- trouble seeing
If aPCC (FEIBA®) is needed, patients should talk to their healthcare provider in case they feel they need more than 100 U/kg of aPCC (FEIBA®) total.
Before using HEMLIBRA, patients should tell their healthcare provider about all of their medical conditions, including if they:
• are pregnant or plan to become pregnant. It is not known if HEMLIBRA may harm an unborn baby. Females who are able to become pregnant should use birth control (contraception) during treatment with HEMLIBRA.
• are breastfeeding or plan to breastfeed. It is not known if HEMLIBRA passes into breast milk.
What should patients know about lab monitoring?
HEMLIBRA may interfere with laboratory tests that measure how well blood is clotting and may cause a false reading. Patients should talk to their healthcare provider about how this may affect their care.
The most common side effects of HEMLIBRA include: redness, tenderness, warmth, or itching at the site of injection; headache; and joint pain.
These are not all of the possible side effects of HEMLIBRA. Patients should call their doctor for medical advice about side effects.
Side effects may be reported to the FDA at 800-FDA-1088 or fda.gov/medwatch. Side effects may also be reported to Genentech at 888-835-2555.
Please see the HEMLIBRA full Prescribing Information and the Medication Guide, including Serious Side Effects, for more important safety information.
About hemophilia A
Hemophilia A is an inherited, serious disorder in which a person’s blood does not clot properly, leading to uncontrolled and often spontaneous bleeding. Hemophilia affects around 20,000 people in the United States, with hemophilia A being the most common form and approximately 50-60 percent of people living with a severe form of the disorder.
People with hemophilia 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 hemophilia A can bleed frequently, especially into their joints or muscles. 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.
A serious complication of treatment is the development of inhibitors to factor VIII replacement therapies. Inhibitors are antibodies developed by the body’s immune system that bind to and block the efficacy of replacement factor VIII, making it difficult, if not impossible, to obtain a level of factor VIII sufficient to control bleeding.
About Genentech in hemophilia
In 1984, Genentech scientists were the first to clone recombinant factor VIII in response to the contaminated hemophilia blood supply crisis of the early 1980s. For more than 20 years, Genentech (gene.com/hemophilia) has been developing medicines to bring innovative treatment options to people with diseases of the blood within oncology, and in hemophilia A. Genentech is committed to improving treatment and care in the hemophilia community by delivering meaningful science and clinical expertise.
Founded more than 40 years ago, Genentech (gene.com) is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California.