Monday, Jun 4, 2018

FDA Grants Priority Review to Genentech’s HEMLIBRA (emicizumab-kxwh) for People With Hemophilia A Without Factor VIII Inhibitors

South San Francisco, CA -- June 4, 2018 --

Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the U.S. Food and Drug Administration (FDA) has accepted the company’s supplemental Biologics License Application (sBLA) and granted Priority Review for HEMLIBRA® (emicizumab-kxwh) for adults and children with hemophilia A without factor VIII inhibitors. The sBLA is based on data from the Phase III HAVEN 3 study. The FDA is expected to make a decision on approval by October 4, 2018.

“People with hemophilia A can face significant challenges in managing their condition and may need to adapt their daily lives to avoid bleeds and accommodate treatment,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We believe the FDA’s decision to grant Priority Review to HEMLIBRA underscores its potential to improve the standard of care for people without factor VIII inhibitors and to help reduce treatment burden by offering more flexible subcutaneous dosing options. We look forward to working with the FDA to hopefully bring HEMLIBRA to all people with hemophilia A as quickly as possible.”

In the HAVEN 3 study, adults and adolescents aged 12 years or older with hemophilia A without factor VIII inhibitors who received HEMLIBRA prophylaxis every week or every two weeks showed a 96 percent (p<0.0001) and 97 percent (p<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis. In an additional arm of the study, people who had previously received factor VIII prophylaxis in a non-interventional study switched to HEMLIBRA prophylaxis, allowing for an intra-patient comparison of two prophylaxis regimens. Based on the intra-patient comparison, HEMLIBRA demonstrated a statistically significant reduction of 68 percent (p<0.0001) in treated bleeds, making it the first medicine to show superior efficacy to prior treatment with factor VIII prophylaxis, the 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 in the HAVEN 3 study were injection site reactions, joint pain (arthralgia), common cold symptoms (nasopharyngitis), headache, upper respiratory tract infection and influenza. Results from the HAVEN 3 study were presented at the World Federation of Hemophilia (WFH) 2018 World Congress in May.

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. The FDA granted Breakthrough Therapy Designation for HEMLIBRA in people with hemophilia A without factor VIII inhibitors in April 2018 based on data from the HAVEN 3 study. 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. Data from the HAVEN 3 study have also been submitted for approval consideration to the European Medicines Agency. Submissions to other regulatory authorities around the world are ongoing.

HEMLIBRA was approved by the FDA in November 2017 for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors based on results from the HAVEN 1 and HAVEN 2 studies. HEMLIBRA was also recently approved by regulatory authorities in other countries around the world, including by the European Commission in February 2018 for routine prophylaxis of bleeding episodes in people with hemophilia A with factor VIII inhibitors.

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.

In the Phase III HAVEN 3 study, adults and adolescents aged 12 years or older without factor VIII inhibitors who received HEMLIBRA prophylaxis every week or every two weeks showed a 96 percent (p<0.0001) and 97 percent (p<0.0001) reduction in treated bleeds, respectively, compared to those who received no prophylaxis. In addition, 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. Importantly, in an intra-patient comparison in patients who were previously enrolled in a prospective non-interventional study (NIS), once-weekly HEMLIBRA prophylaxis showed superior efficacy compared to prior factor VIII prophylaxis, the standard of care for people with hemophilia A without factor VIII inhibitors, as demonstrated by a 68 percent reduction (p<0.0001) in treated bleeds.

There were no unexpected or serious adverse events (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 in the HAVEN 3 study 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 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

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:

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

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:

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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