FDA Approves Efanesoctocog Alfa to Treat Hemophilia A

The FDA has approved efanesoctocog alfa (Altuviiio), a recombinant factor VIII therapy with once-a-week dosing, for patients with hemophilia A. With a longer half-life, patients may only need weekly dosing instead of infusions 2 to 3 times a week. The FDA’s decision comes ahead of the target action date for the decision on February 28, 2023.

Efanesoctocog alfa is the first factor VIII therapy that has been shown to break through the von Willebrand factor ceiling, which imposes a half-life limitation on earlier generation factor VIII therapies.

"Today’s approval of Altuviiio allows patients and physicians to reimagine living with hemophilia,” Paul Hudson, CEO of Sanofi, said in a statement.¹ “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.

Patients with hemophilia A have an impaired blood clotting ability, which causes excessive bleeds and spontaneous bleeds into joints, which causes joint damage and chronic pain. 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.

The approval was supported by data from the pivotal phase 3 XTEND-1 study (NCT04161495), which was published in New England Journal of Medicine.² This open-label, global, nonrandomized, interventional study assessed the safety, efficacy, and pharmacokinetics of once-weekly efanesoctocog alfa with severe hemophilia A who were previously treated with factor VIII replacement therapy.

The study included 159 patients aged 12 years or older, and it had 2 parallel treatment arms. In prophylaxis arm A, 133 patients were treated with IV efanesoctocog alfa (50 IU per kilogram of body weight) prophylaxis once a week for 52 weeks. In the on-demand arm B, 26 patients who had received prior on-demand factor VIII therapy began 26 weeks of on-demand efanesoctocog alfa before switching to once-weekly prophylaxis for an additional 26 weeks.

The median annualized bleeding rate was 0 for group A. Overall, 97% of bleeding episodes resolved with 1 injection of efanesoctocog alfa.

“We are excited about the potential for efanesoctocog alfa to address unmet needs by allowing people living with hemophilia to enjoy an active lifestyle,” Angela Weyand, MD, investigator of XTEND-1 and associate professor at Michigan Medicine, said in a statement.³ “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. 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.”

The study found efanesoctocog alfa prophylaxis improved physical health (P < .001), pain intensity (P = .03), and joint health (P = .01) when comparing 52-week with baseline measurements.

The most common treatment-emergency adverse events, occurring in > 5% of overall participants, were headache, arthralgia, fall, and back pain.

References

1. FDA approves once-weekly Altuviiio a new class of factor VIII therapy for hemophilia A that offers significant bleed protection. News release. Sanofi. February 23, 2023. Accessed February 24, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-02-23-21-00-00-2614759

2. von Drygalski A, Chowdary P, Kulkarni R, et al; XTEND-1 Trial Group. Efanesoctocog alfa prophylaxis for patients with severe hemophilia A. N Engl J Med . 2023;388(4):310-318. doi:10.1056/NEJMoa2209226

3. NEJM publishes once-weekly efanesoctocog alfa Phase 3 data demonstrating its potential to transform the treatment landscape for people with hemophilia A. News release. Sanofi. January 25, 2023. Accessed February 24, 2023. https://www.sanofi.com/en/media-room/press-releases/2023/2023-01-25-22-30-00-2595681