Genentech recently announced positive data from a pair of phase III studies designed to evaluate the prophylactic use of emicizumab in adults, adolescents and children with hemophilia A and inhibitors to factor VIII (FVIII). The two multicenter studies are designated HAVEN 1 for adult and adolescent participants, and HAVEN 2 for child participants.
Emicizumab is being co-developed by Chugai, Roche and Genentech for the prophylactic treatment of people with FVIII deficiency, or hemophilia A, both with and without inhibitors. Unlike existing treatments, which require intravenous injections, emicizumab is administered subcutaneously via an injection just under the skin.
Emicizumab 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 clot formation. In this case, emicizumab binds to and bridges two other key clotting proteins, activated factor IX and factor X, important components of the cascade normally performed by FVIII.
Phase III HAVEN 1 is designed to evaluate the efficacy, safety, and pharmacokinetics of emicizumab prophylaxis and compare it with on-demand and prophylactic use of bypassing agents in adults and adolescents with hemophilia A with inhibitors. Included in the study are 109 patients, 12 years of age or older, who were previously treated with on-demand or prophylactically with bypassing agents. Results showed a statistically significant and clinically meaningful reduction in bleed rate of 87% with emicizumab prophylaxis compared to on-demand treatment with bypassing agents. After a median observation time of 31 weeks, 62.9% of patients receiving emicizumab prophylactically experienced zero treated bleeds compared to 5.6% of those receiving on-demand bypassing agents.
Phase III HAVEN 2 is designed to measure the efficacy, safety, pharmacokinetics, health-related HRQoL and “proxy HRQoL” – includes caregiver burden – associated with once-weekly injection 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 FVIII, who require treatment with bypassing agents. Study investigators ultimately look to enroll a total of 60 children for its final analysis planned after 52 weeks of treatment.
Interim results indicate that children who receive emicizumab prophylaxis are 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 data also indicate that the same dose of emicizumab is appropriate for children as for adults and adolescents, based on the pharmacokinetics of the children compared with the level of emicizumab in the blood of adults and adolescents.
Data from both studies will be presented at the upcoming 26th International Society on Thrombosis and Haemostasis Meeting, July 10, 2017, in Berlin, Germany.
Source: Genentech press release dated June 25, 2017
