NEJM Publishes Positive Study of Sanofi’s Experimental Once Weekly Therapy for Hemophilia A

Rare Daily Staff

Pivotal study data published in The New England Journal of Medicine show that Sanofi’s experimental hemophilia A therapy efanesoctocog alfa met primary and key secondary endpoints, demonstrating clinically meaningful prevention of bleeds and superior bleed protection compared to prior factor VIII prophylaxis.

Treatment with efanesoctocog alfa prophylaxis resulted in significant and clinically meaningful improvements in physical health, pain, and joint health. This included a 77 percent reduction in annualized bleeding rates compared to prior factor VIII prophylaxis. Nearly all (97 percent) bleeding episodes resolved with a single injection of efanesoctocog alfa.

Hemophilia A is a rare, lifelong condition in which the ability of a person’s blood to clot properly is impaired, leading to excessive bleeds that can result in joint damage and chronic pain, and potentially impact their quality of life. The severity of hemophilia is determined by the level of clotting factor activity in a person’s blood.

Efanesoctocog alfa is a novel and experimental recombinant factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for people with hemophilia A. It builds on the innovative Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation. It is the first experimental factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on current factor VIII therapies. Altuviiio is the intended trade name of efanesoctocog alfa in the United State, but it could differ in other territories as per the local regulatory requirements, formerly known as BIVV001.

Efanesoctocog alfa is currently under U.S. Food and Drug Administration review and the target action date for the decision is February 28, 2023. The FDA also granted efanesoctocog alfa Breakthrough Therapy, Fast Track, and Orphan Drug designations.

Sanofi expects to make a regulatory submission in the European Union in the second half of 2023. It will follow availability of data from the ongoing, fully recruited XTEND-Kids pediatric study, expected in the first half of 2023. The European Commission granted efanesoctocog alfa orphan designation in June 2019. Sanofi and Sobi collaborate on the development of efanesoctocog alfa.

The phase 3 XTEND-1 study was an open-label, non-randomized interventional study assessing the safety, efficacy, and pharmacokinetics of once-weekly efanesoctocog alfa in people 12 years of age or older with severe hemophilia A who were previously treated with factor VIII replacement therapy. The study consisted of two parallel treatment arms—the prophylaxis Arm A, in which patients who had received prior factor VIII prophylaxis were treated with once-weekly intravenous efanesoctocog alfa prophylaxis for 52 weeks, and the on-demand Arm B, in which patients who had received prior on-demand factor VIII therapy began 26 weeks of on-demand efanesoctocog alfa, then switched to once-weekly prophylaxis for an additional 26 weeks.

“Based on the XTEND-1 study results assessing efanesoctocog alfa, we have the opportunity to provide near normal factor activity levels for an extended period of time (the majority of a week) with a single dose, which is a first for hemophilia A,” said Angela Weyand, investigator of the XTEND-1 clinical trial and associate professor at Michigan Medicine. “The data show that efanesoctocog alfa can offer patients increased bleed protection, leading to improved outcomes, such as reduced pain and improved physical functioning, that may impact daily life with a reduced treatment burden.”

Photo: Angela Weyand, investigator of the XTEND-1 clinical trial and associate professor at Michigan Medicine