The FDA decision announced on Thursday (February 23) marks the first approval of Altuviiio: while regulatory submission in the EU is anticipated in the second half of 2023.
Altuviiio is indicated for routine prophylaxis and on-demand treatment to control bleeding episodes, as well as perioperative management (surgery) for adults and children with hemophilia A.
It is the first and only hemophilia A treatment that delivers normal to near-normal factor activity levels (over 40%) for most of the week with once-weekly dosing, and significantly reduces bleeds compared to prior factor VIII prophylaxis.
Once-weekly prophylactic dosing
Hemophilia A - a rare, genetic disorder in which the ability of a person’s blood to clot is impaired due to a missing or defective factor VIII clotting protein – is usually treated by factor replacement therapy.
Altuviiio is a recombinant factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for people with hemophilia A.
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 and spontaneous bleeds into joints that can result in joint damage and chronic pain, and potentially impact quality of life. The severity of hemophilia is determined by the level of clotting factor activity in a person’s blood, and there is a negative correlation between risk of bleeding and factor activity levels.
Until 1992, all factor replacement products were made from human plasma. In 1992, the FDA approved recombinant factor VIII concentrate, which – among other aspects – removes the risk of transmitting infectious agents.
Most factor proteins are cleared from the body quickly: meaning many people with hemophilia A need to inject replacement factor several times a week.
A companion protein, von Willebrand factor (vWF), protects factor VIII from being broken down, but itself gets cleared by the body.
Sanofi & Sobi’s Efanesoctocog alfa is a therapy building on Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation – making it the first investigational factor VIII therapy that has been shown to break through the von Willebrand factor ceiling.
Data from the XTEND-1 Phase 3 study published in the NEJM early this month show that efanesoctocog alfa met primary and key secondary endpoints, demonstrating ‘clinically meaningful prevention of bleeds and superior bleed protection compared to prior factor VIII prophylaxis based on an intra-patient comparison.
Treatment with efanesoctocog alfa prophylaxis resulted in significant and clinically meaningful improvements in physical health, pain, and joint health’.
Responding to the FDA approval, Sanofi CEO Paul Hudson said: "The approval of Altuviiio allows patients and physicians to reimagine living with hemophilia. The high sustained factor activity levels that can be achieved with Altuviiio have the potential to change the hemophilia landscape. For the first time, with a once-weekly dose, powerful bleed protection is a reality for patients.”
Lynn Malec, MD, Medical Director of Comprehensive Center for Bleeding Disorders and Associate Investigator at The Versiti Blood Research Institute, and Associate Professor of Medicine and Pediatrics at The Medical College of Wisconsin, added: “This approval marks an important clinical advancement for the hemophilia community because we have an option that can achieve higher levels of factor activity with a single simplified weekly dose. By maintaining high levels of factor activity throughout the week, patients can be confident in the bleed protection Altuviiio offers.”