Once-weekly efanesoctocog alfa data shows ‘potential to transform the treatment landscape for hemophilia A’, says Sanofi

By Rachel Arthur

- Last updated on GMT


Related tags Sanofi Hemophilia

Phase 3 data for efanesoctocog alfa has been published in the New England Journal of Medicine (NEJM): ahead of a decision on the therapy by the US Food and Drug Administration (FDA) at the end of next month.

The newly published data demonstrates that efanesoctocog alfa delivered ‘normal to near-normal factor activity levels’ (>40%) for the majority of the week with once-weekly dosing – described as a first for hemophilia A.

The Biologics License Application (BLA) for efanesoctocog alfa - a collaboration between Sanofi and Stockhold-headquartered Sobi - is currently under priority review by the FDA with a target action date for the decision as February 28, 2023. It was also the first factor VIII therapy to receive FDA breakthrough therapy designation (May 2022); and has also gained orphan drug designation (August 2017).

Regulatory submission in the EU is expected to follow in the second half of 2023, using data from the ongoing XTEND-Kids paediatric study (due in the first half of 2023). The European Commission granted efanesoctocog alfa orphan designation in June 2019. 

Prophylactic treatment

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.

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.

Efanesoctocog alfa – which is expected to be known as Altuviiio if it gains FDA approval - is a novel and investigational recombinant factor VIII therapy that is designed to extend protection from bleeds with once-weekly prophylactic dosing for people with hemophilia A.

The data from the pivotal XTEND-1 Phase 3 study published in the NEJM 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’. 

“We are steadfast in our commitment to developing novel treatment options that have a meaningful impact for patients," ​said Dietmar Berger, MD, PhD, Global Head of Development and Chief Medical Officer at Sanofi.

"We are hopeful that Altuviiio (efanesoctocog alfa) will help deliver on this goal by offering unprecedented factor activity levels with once-weekly dosing, fulfilling its potential as a best-in-class therapy for hemophilia A.”

Sobi has final development and commercialization rights in the Sobi territory (Europe, North Africa, Russia and most Middle Eastern markets).

Sanofi has final development and commercialization rights in North America and all other regions in the world.

The two companies also collaborate on hemophilia B treatment Alprolix and hemophilia A treatment Elocta.

Key results from the Phase 3 XTEND-1 study, published in NEMJ,​ include:

  • The median and mean annualized bleeding rates (ABR) were 0.00 (IQR: 0.00-1.04) and 0.71 (95% CI: 0.52-0.97), respectively.
  • A 'statistically significant and clinically meaningful reduction in ABR' (77%) versus prior factor VIII prophylaxis (p<0.001).
  • Nearly all (97%) bleeding episodes resolved with a single injection of efanesoctocog alfa (50 IU/kg).
  • Efanesoctocog alfa provided mean factor activity >40 IU/dL for the majority of the week and at 15 IU/dL at Day 7.
  • Efanesoctocog alfa prophylaxis improved physical health (p<0.001), pain intensity (p=0.03), and joint health (p=0.01) when comparing 52 week and baseline measurements.i
  • In patients with target joints at baseline, 100% of the target joints were resolved after at least 12 months of continuous prophylaxis.
  • Efanesoctocog alfa was well-tolerated, and inhibitor development to factor VIII was not detected. The most common treatment-emergent adverse events (>5% of participants overall) were headache, arthralgia, fall, and back pain.

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