Sanofi announced Pivotal study data published in The New England Journal of Medicine (NEJM) continues to highlight the efficacy, safety, and pharmacokinetic profile of efanesoctocog alfa (formerly BIVV001), a potential new medicine for haemophilia A. These data demonstrate the clinical benefits of normal to near-normal factor activity levels (>40%) for the majority of the week achieved by once weekly efanesoctocog alfa dosing. Efanesoctocog alfa is currently under priority regulatory review in the US with a target action date of 28 February 2023. Haemophilia 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 quality of life.

The severity of haemophilia is determined by the level of clotting factor activity in a person's blood. The data from the pivotal XTEND-1 phase 3 study results published in NEJM show that efanesoctocog alfa met primary and key secondary endpoints, demonstrating clinically meaningful prevention of bleeds and superior bleed protection compared to prior prophylaxis based on an intra-patient comparison. Treatment with efanesoctocog alfa prophylaxis also resulted in significant and clinically meaningful improvements in physical health, pain, and joint health.

Key results include: The median and mean annualised bleeding rates (ABR) were 0.00 (interquartile range: 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). 97% of 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 on 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. 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. The XTEND-1 phase 3 study (NCT04161495) was an open-label, non-randomised interventional study assessing the safety, efficacy and pharmacokinetics of once-weekly efanesoctocog alfa in people 12 years of age or older (n=159) with severe haemophilia A who were previously treated with factor VIII replacement therapy. The study consisted of two parallel treatment arms- the prophylaxis arm A (n=133), in which patients who had received prior factor VIII prophylaxis were treated with once-weekly intravenous efanesoctocog alfa prophylaxis (50 IU/kg) for 52 weeks, and the on-demand arm B (n=26), in which patients who had received prior on-demand factor VIII therapy began 26 weeks of on-demand efanesoctocog alfa (50 IU/kg), then switched to once-weekly prophylaxis (50 IU/kg) for an additional 26 weeks.

The primary efficacy endpoint was the annualised bleeding rate (ABR) in arm A, and the key secondary endpoint was an intra-patient comparison of ABR during the efanesoctocog alfa weekly prophylaxis treatment period versus the prior factor VIII prophylaxis ABR for participants in arm A who had participated in a previous observational study (Study 242HA201/OBS16221).