FDA Approves Once-Weekly Subcutaneous Therapy for Hemophilia A Patients with Inhibitors
The U.S. Food and Drug Administration (FDA) has approved HEMLIBRA® (emicizumab) for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors. The once-weekly therapy was co-developed by Chugai, Roche and Genentech. While existing factor therapies are delivered intravenously, HEMLIBRA® is unique in that it is administered subcutaneously via an injection just under the skin.
HEMLIBRA® is a laboratory-engineered protein that works by performing a key function in the clotting cascade that is normally carried out by the FVIII protein, which is deficient in individuals with hemophilia A. The “cascade” is an intricate series of chemical and molecular reactions between clotting factors that lead to the formation of viable clot. In this case, HEMLIBRA® binds to and bridges two other key clotting proteins, activated factor IX and factor X, important components of the cascade normally performed by FVIII.
The FDA approval was based in large part on two phase III clinical studies known as HAVEN 1 and HAVEN 2. HAVEN 1 was designed to evaluate the efficacy, safety, and pharmacokinetics of HEMLIBRA® prophylaxis and compare it with on-demand and prophylactic use of bypassing agents (BPAs) in adults and adolescents 12 years of age or older with hemophilia A with inhibitors. The results showed an 87% reduction in treated bleeds compared to those who received no prophylaxis. According to the Genentech press release, in a “first-of-its-kind” intra-patient analysis, HEMLIBRA® prophylaxis resulted in a statistically significant reduction in treated bleeds of 79% compared to previous treatment with BPAs prophylaxis collected in a non-interventional study prior to enrollment.
HAVEN 1 also included patient-reported quality of life data on physical health, which showed that patients treated with the therapy reported an improvement in hemophilia-related symptoms (painful swellings and joint pain) and physical functioning (pain with movement and difficulty walking) compared to patients who did not receive prophylactic treatment.
HAVEN 2 was designed to measure the efficacy, safety, pharmacokinetics of HEMLIBRA® prophylaxis in children younger than 12 years of age with hemophilia A with inhibitors to FVIII, who require treatment with BPAs. Interim results showed that 87% of children who received HEMLIBRA® prophylaxis experienced zero treated bleeds. In an intra-patient analysis of 13 children, prophylaxis with HEMLIBRA® resulted in a 99% reduction in treated bleeds compared to previous treatment with a BPA either as prophylaxis or on-demand.
"Reducing the frequency or preventing bleeding episodes is an important part of disease management for patients with hemophilia. Today’s approval provides a new preventative treatment that has been shown to significantly reduce the number of bleeding episodes in patients with hemophilia A with factor VIII inhibitors,” said Richard Pazdur, MD, acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence. “In addition, patients treated with HEMLIBRA reported an improvement in their physical functioning.”
Source: Genentech press release dated November 16, 2017