FDA Approves Genentech’s Hemlibra

South San Francisco, CA  October 4, 2018 Press Release

FDA Approves Genentech’s Hemlibra (Emicizumab-kxwh) for Hemophilia A Without Factor VIII Inhibitors

First medicine to significantly reduce treated bleeds compared to prior factor VIII prophylaxis based on an intra-patient comparison

Only medicine that can be self-administered subcutaneously once weekly, every two weeks or every four weeks for hemophilia A with and without factor VIII inhibitors

The efficacy and safety of Hemlibra has been demonstrated in one of the largest pivotal clinical trial programs in hemophilia A

SOUTH SAN FRANCISCO, CA — 2018-10-04 00:00:00

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has approved Hemlibra^® (emicizumab-kxwh) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children, ages newborn and older, with hemophilia A without factor VIII inhibitors. Hemlibra is now the only prophylactic treatment for people with hemophilia A with and without factor VIII inhibitors that can be administered subcutaneously (under the skin) and at multiple dosing options (once weekly, every two weeks or every four weeks). This approval is based on positive results from the Phase III HAVEN 3 and HAVEN 4 studies. Hemlibra prophylaxis led to statistically significant and clinically meaningful reductions in treated bleeds compared to no prophylaxis (primary endpoint) and across all other bleed-related endpoints in the HAVEN 3 study, and showed a clinically meaningful control of bleeding in the HAVEN 4 study.

“Many preventative treatment options for people with hemophilia A without factor VIII inhibitors require intravenous infusions several times a week. Even then, people can still experience bleeds, and there has been a need for more treatment options,” said Michael Callaghan, M.D., hematologist, Children’s Hospital of Michigan. “The approval of Hemlibra is an important advancement for the entire hemophilia A community, as we now have a new class of medicine for the first time in nearly 20 years. Hemlibra can reduce bleeds, and it offers a new subcutaneous administration once weekly, every two weeks or every four weeks.”

“Today’s approval of Hemlibra reflects our commitment to groundbreaking science and the development of medicines with the potential to redefine the standard of care,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Hemlibra is now the only FDA-approved medicine for people with hemophilia A with and without factor VIII inhibitors, based on the efficacy and safety profile demonstrated across four pivotal studies. We want to thank the hemophilia community for their partnership in helping us bring this new option to everyone living with hemophilia A.”

In the Phase III HAVEN 3 study, adults and adolescents aged 12 years or older with hemophilia A without factor VIII inhibitors who received Hemlibra prophylaxis once weekly (n=36) or every two weeks (n=35) experienced a 96 percent (95 percent CI: 92.5; 98.0, p<0.0001) and 97 percent (95 percent CI: 93.4; 98.3, p<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis (n=18). Hemlibra is the first medicine to significantly reduce treated bleeds compared to prior factor VIII prophylaxis, which has been the recommended standard of care, as demonstrated by a statistically significant reduction of 68 percent (95 percent CI: 48.6; 80.5, p<0.0001) in treated bleeds in a prospective intra-patient comparison (n=48) of people who previously received factor VIII prophylaxis in a non-interventional study and switched to Hemlibra prophylaxis. In the single-arm Phase III HAVEN 4 study of adults and adolescents aged 12 years or older with hemophilia A with factor VIII inhibitors (n=5) and without factor VIII inhibitors (n=36), Hemlibra prophylaxis every four weeks (n=41) led to clinically meaningful control of bleeding. The most common adverse reactions occurring in 10 percent or more of people treated with Hemlibra in pooled studies (n=391) were injection site reactions (n=85), headache (n=57) and joint pain (arthralgia; n=59).

Hemlibra is now available to people in the U.S. who have hemophilia A without factor VIII inhibitors. Genentech is committed to helping people with hemophilia A access Hemlibra and offers comprehensive services to help minimize barriers to access and reimbursement. Patients can call (866) HEMLIBRA (436-5427) for more information. For people who qualify, Genentech also offers patient assistance programs through Genentech Access Solutions. More information is available at (877) 233-3981 or http://www.Genentech-Access.com/Hemlibra.

Hemlibra was granted Breakthrough Therapy Designation by the FDA for hemophilia A without factor VIII inhibitors. It was also granted Priority Review, a designation given 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.

Hemlibra was approved by the FDA in November 2017 for adults and children with hemophilia A with factor VIII inhibitors. It has been studied in one of the largest pivotal clinical trial programs in people with hemophilia A with and without factor VIII inhibitors, including four pivotal HAVEN studies (HAVEN 1, HAVEN 2, HAVEN 3 and HAVEN 4).

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 four weeks, followed by 1.5 mg/kg/wk for at least 24 weeks (Arm A; n=36), subcutaneous Hemlibra prophylaxis at 3 mg/kg/wk for four weeks, followed by 3 mg/kg/2wks (Arm B; n=35) for at least 24 weeks or no prophylaxis (Arm C; n=18) for at least 24 weeks. Patients previously treated with factor VIII prophylaxis received subcutaneous Hemlibra prophylaxis at 3 mg/kg/wk for four weeks, followed by 1.5 mg/kg/wk until the end of study (Arm D; n=48). Episodic treatment of breakthrough bleeds with factor VIII therapy was allowed per protocol.

HAVEN 3 met its primary endpoint and key secondary endpoints. Data from the study showed:

• Hemlibra prophylaxis once weekly or every two weeks resulted in a 96 percent (95 percent CI: 92.5; 98.0, p<0.0001) and 97 percent (95 percent CI: 93.4; 98.3, 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 once weekly 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 once weekly 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 once weekly or every two weeks resulted in a 95 percent (95 percent CI: 85.7; 98.4, p<0.0001) and 95 percent (95 percent CI: 85.3; 98.2, p<0.0001) reduction in treated target joint bleeds, respectively, compared to no prophylaxis.
• Hemlibra prophylaxis once weekly or every two weeks resulted in a 95 percent (95 percent CI: 90.1; 97.0, p<0.0001) and 94 percent (95 percent CI: 89.7; 97.0, p<0.0001) reduction in all bleeds, respectively, compared to no prophylaxis.
• Hemlibra prophylaxis once weekly demonstrated a statistically significant reduction of 68 percent (95 percent CI: 48.6; 80.5, p<0.0001) in treated bleeds compared to prior factor VIII prophylaxis based on a prospective intra-patient comparison of people who were previously enrolled in a non-interventional study.
• The most common adverse reactions occurring in 10 percent or more of people treated with Hemlibra in pooled studies (n=391) were injection site reactions (n=85), headache (n=57) and joint pain (arthralgia; n=59).

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. In the expansion cohort (n=41), patients with hemophilia A with factor VIII inhibitors (n=5) and without factor VIII inhibitors (n=36) 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.

In the HAVEN 4 study, 56.1 percent (95 percent CI: 39.7; 71.5) of people with or without factor VIII inhibitors treated with Hemlibra prophylaxis every four weeks experienced zero treated bleeds and 90.2 percent (95 percent CI: 76.9; 97.3) experienced three or fewer treated bleeds.

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, every two weeks or every four weeks. 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, ages newborn and older, with hemophilia A with or without factor VIII inhibitors.

Important Safety Information

What is the most important information to know about Hemlibra? 

Hemlibra increases the potential for blood to clot. Patients should carefully follow their healthcare provider’s instructions regarding when to use an on-demand bypassing agent or factor VIII, and the dose and schedule to use for breakthrough bleed treatment. Hemlibra may cause the following serious side effects when used with activated prothrombin complex concentrate (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 the 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.

Patients should tell their healthcare provider about all the medicines they take,  including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements. Patients should keep a list of them to show their healthcare provider and pharmacist when they get a new medicine.

How should patients use Hemlibra?

Patients should see the detailed “Instructions for Use” that comes with Hemlibra for information on how to prepare and inject a dose of Hemlibra, and how to properly throw away (dispose of) used needles and syringes. 

•  Stop (discontinue) prophylactic use of bypassing agents the day before starting Hemlibra prophylaxis. 
•  Patients may continue prophylactic use of factor VIII for the first week of Hemlibra prophylaxis. 

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 speak to their healthcare provider for medical advice about side effects.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Patients should not use Hemlibra for a condition for which it was not prescribed. Patients should not give Hemlibra to other people, even if they have the same symptoms that they have. It may harm them. Patients can ask their pharmacist or healthcare provider for information about Hemlibra that is written for health professionals.

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 Medication Guide for more important safety information including Serious Side Effects.

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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