Wednesday, Aug 23, 2017

FDA Grants Priority Review to Genentech's Emicizumab for Hemophilia A with Inhibitors

Application based on positive results of Phase III study in adults and adolescents with hemophilia A with inhibitors and interim Phase III results in children

South San Francisco, CA -- August 23, 2017 --

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 Biologics License Application (BLA) and granted Priority Review for emicizumab prophylaxis (preventative) as a once-weekly subcutaneous treatment for adults, adolescents and children with hemophilia A with factor VIII inhibitors. Nearly one in three people with hemophilia A develop inhibitors to standard factor VIII replacement therapies, which limits treatment options and increases the risk of life-threatening bleeds and repeated bleeds, particularly in joints, that cause long-term damage.

“Genentech has a history of developing innovative antibody therapies to address some of the highest unmet medical needs,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “Results of our Phase III study in adults and adolescents as well as early Phase III results in children showed that emicizumab has significant potential to help people with hemophilia A with inhibitors, who face major challenges in preventing and treating bleeds. We are working with the FDA to hopefully bring this new prophylactic treatment option to the hemophilia A inhibitor community as soon as possible.”

The BLA for emicizumab is based on results from the Phase III HAVEN 1 study in adults and adolescents 12 years of age and older, as well as interim results from the Phase III HAVEN 2 study in children younger than 12 years of age. Results from HAVEN 1 were published in The New England Journal of Medicine (NEJM) and results from both studies were presented at the 26th International Society on Thrombosis and Haemostasis (ISTH) Congress in July 2017.

The FDA is expected to make a decision on approval by February 23, 2018. Priority Review designation is granted to medicines that the FDA has determined to have the potential to provide significant improvements in the safety and effectiveness of the treatment, prevention or diagnosis of a serious disease. The FDA granted Breakthrough Therapy Designation for emicizumab in adults and adolescents with hemophilia A with inhibitors in September 2015. 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 both HAVEN 1 and HAVEN 2 have also been submitted for approval consideration to the European Medicines Agency (EMA) and will be reviewed under accelerated assessment. Additional studies evaluating emicizumab in people with hemophilia A both with and without inhibitors and exploring less frequent dosing regimens are ongoing.

About HAVEN 1 (NCT02622321)

HAVEN 1 is a randomized, multicenter, open-label, Phase III study evaluating the efficacy, safety and pharmacokinetics of emicizumab prophylaxis compared to on-demand bypassing agents (BPAs) (no prophylaxis; episodic use only) in adults and adolescents with hemophilia A with inhibitors to factor VIII. The study included 109 patients (12 years of age and older) with hemophilia A with inhibitors to factor VIII, who were previously treated with BPAs on-demand or as prophylaxis. Patients previously treated with on-demand BPAs were randomized in a 2:1 fashion to receive emicizumab prophylaxis (Arm A) or no prophylaxis (Arm B). Patients previously treated with prophylactic BPAs received emicizumab prophylaxis (Arm C). Additional patients previously on BPAs (on-demand or prophylaxis) were also enrolled in a separate arm (Arm D). On-demand treatment of breakthrough bleeds with BPAs was allowed per protocol in all arms.

The primary endpoint of the study is the number of treated bleeds over time with emicizumab prophylaxis (Arm A) compared with no prophylaxis (Arm B). Secondary endpoints include all bleed rate, joint bleed rate, spontaneous bleed rate, target joint bleed rate, health-related quality of life (HRQoL)/health status, and intra-patient comparison to bleed rate on their prior prophylaxis regimen with BPAs (Arm C) or no prophylaxis (Arm B). The study also evaluated safety and pharmacokinetics.

In the HAVEN 1 study, the primary endpoint showed a clinically meaningful and statistically significant reduction in treated bleeds of 87 percent (risk rate [RR]=0.13, p<0.0001) with emicizumab prophylaxis compared with on-demand (no prophylaxis; episodic use only) BPAs. All 12 secondary endpoints were positive, including a statistically significant reduction of 79 percent (RR=0.21, p=0.0003) in treated bleeds in a first-of-its-kind intra-patient analysis comparing two prophylaxis regimens (emicizumab and BPAs) in a subset of patients. Adverse events (AEs) occurring in five percent or more of patients treated with emicizumab were local injection site reactions, headache, fatigue, upper respiratory tract infection and joint pain (arthralgia).

As previously reported, two patients experienced thromboembolic events (TE) and three patients had thrombotic microangiopathy (TMA) while receiving emicizumab prophylaxis and more than 100 u/kg/day of the BPA activated prothrombin complex concentrate on average for 24 hours or more before the event. Two of these patients had also received recombinant factor VIIa. Neither TE event required anti-coagulation therapy and one patient restarted emicizumab. The cases of TMA observed were transient, and one patient restarted emicizumab.

About HAVEN 2 (NCT02795767)

HAVEN 2 is a single-arm, multicenter, open-label, Phase III study evaluating the efficacy, safety and pharmacokinetics of once-weekly subcutaneous administration of emicizumab. The interim analysis after a median of 12 weeks of treatment included 19 children (younger than 12 years of age) with hemophilia A with inhibitors to factor VIII, who require treatment with BPAs. The objectives of the study are to evaluate the number of treated bleeds over time with emicizumab prophylaxis, safety, pharmacokinetics, HRQoL and proxy HRQoL with aspects of caregiver burden.

Interim results from the single-arm HAVEN 2 study were consistent with the positive results from the HAVEN 1 study. After a median observation time of 12 weeks, the study showed that only one of 19 children receiving emicizumab reported a treated bleed. There were no reported joint or muscle bleeds. The study also indicated that emicizumab, with a once-weekly subcutaneous dosing, may help alleviate some of the burden of hemophilia treatment for children and their parents. The most common AEs were mild injection site reactions and common cold symptoms (nasopharyngitis). No TE or TMA events were observed.

About emicizumab (ACE910)

Emicizumab is an investigational bispecific monoclonal antibody designed to bring together factors IXa and X, proteins required to activate the natural coagulation cascade and restore the blood clotting process. Emicizumab is administered by an injection of a ready-to-use solution under the skin (subcutaneously) once weekly. Emicizumab is being evaluated in pivotal Phase III studies in people 12 years of age and older, both with and without inhibitors to factor VIII, and in children younger than 12 years of age with factor VIII inhibitors. Additional trials are exploring less frequent dosing schedules. The clinical development program is assessing the safety and efficacy of emicizumab 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. Emicizumab was created by Chugai Pharmaceutical Co., Ltd. and is being co-developed by Chugai, Roche and Genentech.

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. In addition to impacting a person’s quality of life, these bleeds can be life-threatening if they go into vital organs, such as the brain. 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. People with hemophilia A who develop inhibitors will typically infuse BPA therapies, either on-demand (episodic) or as prophylaxis, to control bleeding. This approach is known to be less effective and less predictable than factor VIII replacement therapy in people with hemophilia A without inhibitors.

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 is investigating emicizumab as a potential treatment option for 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

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 or 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