Positive Phase III Results for Genentech’s HEMLIBRA (emicizumab-kxwh) for Hemophilia A Without Factor VIII Inhibitors Published in New England Journal of Medicine

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, Inc., a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that pivotal data from the Phase III HAVEN 3 study, which evaluated HEMLIBRA^® (emicizumab-kxwh) prophylaxis administered every week or every two weeks in adults and adolescents aged 12 years or older with hemophilia A without factor VIII inhibitors, were published in the August 30, 2018, issue of the New England Journal of Medicine (NEJM).

“In the HAVEN 3 study, HEMLIBRA showed a significant and clinically meaningful reduction in bleeds in people with hemophilia A without factor VIII inhibitors, while offering multiple subcutaneous dosing options,” said Dr. Johnny Mahlangu, Faculty of Health Sciences, University of the Witwatersrand and NHLS, Johannesburg, South Africa. “The publication of these results in the New England Journal of Medicine represents a major advance for hemophilia research and reinforces the potential of HEMLIBRA to change the standard of care for people with hemophilia A.”

“Current prophylactic treatment options for people with hemophilia A can require frequent intravenous infusions, and despite treatment, many continue to have bleeds that can lead to long-term joint damage,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Given the challenges many people face managing their hemophilia, we believe HEMLIBRA could make a meaningful difference, and we are working with health authorities to hopefully make this treatment available to people with hemophilia A without factor VIII inhibitors as soon as possible.”

Data from the HAVEN 3 study showed that HEMLIBRA prophylaxis administered subcutaneously every week or every two weeks significantly reduced treated bleeds by 96 percent (rate ratio [RR]=0.04; p<0.0001) and 97 percent (RR=0.03; p<0.0001), respectively, compared to no prophylaxis. Results also showed that 55.6 percent (95 percent CI: 38.1; 72.1) of people treated with HEMLIBRA every week and 60 percent (95 percent CI: 42.1; 76.1) of people treated with HEMLIBRA every two weeks experienced zero treated bleeds, compared to 0 percent (95 percent CI: 0.0; 18.5) of people treated with no prophylaxis. In an intra-patient comparison of people who previously received factor VIII prophylaxis in a prospective non-interventional study and switched to HEMLIBRA prophylaxis, HEMLIBRA demonstrated a statistically significant reduction of 68 percent (RR=0.32; p<0.0001) in treated bleeds, making it the first medicine to show superior efficacy to prior factor VIII prophylaxis treatment, the current standard of care. There were no unexpected or serious adverse events (AEs) related to HEMLIBRA in the HAVEN 3 study, and the most common AEs were consistent with previous studies. The most common AEs occurring in 5 percent or more of people were injection site reactions, joint pain (arthralgia), common cold symptoms (nasopharyngitis), headache, upper respiratory tract infection and influenza.

Earlier this year, the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation and Priority Review to HEMLIBRA for people with hemophilia A without factor VIII inhibitors based on data from the HAVEN 3 study. The FDA is expected to make a decision on approval by October 4, 2018. Breakthrough Therapy Designation is designed to expedite the development and review of medicines intended to treat a serious condition with preliminary evidence that indicates they may demonstrate substantial improvement over existing therapies. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the treatment, prevention or diagnosis of a serious disease. Submissions to other regulatory authorities around the world are ongoing.

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 for at least 24 weeks (Arm A), subcutaneous HEMLIBRA prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 3 mg/kg/2wks (Arm B) for at least 24 weeks or no prophylaxis (Arm C) for at least 24 weeks. 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.

The Phase III HAVEN 3 study in people with hemophilia A without factor VIII inhibitors met its primary endpoint and key secondary endpoints. Data from the study showed:

• HEMLIBRA prophylaxis every week or every two weeks resulted in a 96 percent (RR=0.04; p<0.0001) and 97 percent (RR=0.03; p<0.0001) reduction in treated bleeds, respectively, compared to no prophylaxis.
• 55.6 percent (95 percent CI: 38.1, 72.1) of people treated with HEMLIBRA every week and 60 percent (95 percent CI: 42.1, 76.1) of people treated with HEMLIBRA every two weeks experienced zero treated bleeds, compared to 0 percent (95 percent CI: 0.0; 18.5) of people treated with no prophylaxis.
• 91.7 percent (95 percent CI: 77.5, 98.2) of people treated with HEMLIBRA prophylaxis every week and 94.3 percent (95 percent CI: 80.8, 99.3) of people treated with HEMLIBRA prophylaxis every two weeks experienced three or fewer treated bleeds, compared to 5.6 percent (95 percent CI: 0.1, 27.3) of people treated with no prophylaxis.
• HEMLIBRA prophylaxis every week or every two weeks resulted in a 95 percent (RR=0.05; p<0.0001) and 95 percent (RR=0.05; p<0.0001) reduction in treated target-joint bleeds, respectively, compared to no prophylaxis.
• HEMLIBRA prophylaxis every week or every two weeks resulted in a 95 percent (RR=0.05; p<0.0001) and 94 percent (RR=0.06; p<0.0001) reduction in all bleeds, respectively, compared to no prophylaxis.
• HEMLIBRA prophylaxis every week demonstrated a statistically significant reduction of 68 percent (RR=0.32; p<0.0001) in treated bleeds compared to prior factor VIII prophylaxis based on an intra-patient comparison of people who were previously enrolled in a prospective non-interventional study.
• There were no unexpected or serious AEs related to HEMLIBRA, and the most common AEs were consistent with previous studies. No thrombotic events or cases of thrombotic microangiopathy were observed. The most common AEs occurring in 5 percent or more of people were injection site reactions, joint pain (arthralgia), common cold symptoms (nasopharyngitis), headache, upper respiratory tract infection and influenza.

About HEMLIBRA

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 globally 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 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:
  • confusion
  • weakness
  • 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
  • headache
  • 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 http://www.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 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. For more information visit http://www.gene.com/hemophilia.

About Genentech

Founded more than 40 years ago, Genentech 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. For additional information about the company, please visit http://www.gene.com.

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