RARE Daily

Sanofi and Sobi Report Positive Pivotal Data of Hemophilia Therapy

July 11, 2022

Sanofi and Swedish Orphan Biovitrum presented positive results from the XTEND-1 pivotal phase 3 study evaluating efanesoctocog alfa, BIVV001, their experimental factor VIII replacement therapy in previously treated adults and adolescents 12 years and older with a severe form of the rare bleeding disorder hemophilia A.

Photo: Anders Ullman, head of R&D and chief medical officer of Sobi

The companies presented the results in a late-breaking session at the 30th International Society on Thrombosis and Haemostasis (ISTH) Congress.

The study met the primary efficacy endpoint, with once-weekly efanesoctocog alfa prophylaxis providing clinically meaningful bleed protection for people with severe hemophilia A. The median annualized bleeding rates (ABR) was 0.00 and the mean ABR was 0.71.

The study also met the key secondary endpoint, demonstrating superior bleed protection over prior factor VIII prophylaxis with an estimated ABR reduction of 77 percent and a mean ABR reduction of 0.69 compared to 2.96 on prior prophylaxis, based on an intra-patient comparison. In a subset of 17 participants studied at baseline and week 26, mean factor VIII levels remained in the normal to near-normal range for the majority of the week, and at 15 IU/dL at day seven post-dose, providing increased factor activity level protection for patients with once-weekly prophylaxis.

Hemophilia A is a rare, genetic disorder in which the ability of a person’s blood to clot is impaired due to a lack of factor VIII. Hemophilia A occurs in about one in 5,000 male births annually, and more rarely in females. People with hemophilia can experience bleeding episodes that can cause pain, irreversible joint damage, and life-threatening hemorrhages. Factor replacement therapy remains a cornerstone of care and can be used across multiple treatment scenarios.

Efanesoctocog alfa, formerly BIVV001, 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 Fc fusion technology by adding a region of von Willebrand factor and XTEN polypeptides to extend its time in circulation. It is the first investigational 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. Efanesoctocog alfa is currently under clinical investigation and its safety and efficacy have not been evaluated by any regulatory authority.

The U.S Food and Drug Administration granted efanesoctocog alfa Breakthrough Therapy Designation in May 2022, Fast Track designation in February 2021 and Orphan Drug designation in August 2017. The European Commission also granted efanesoctocog alfa Orphan Drug designation in June 2019. Regulatory submission of the Biologics License Application to the U.S. FDA occurred in June 2022 and submission in the EU will follow availability of data from the ongoing XTEND-Kids pediatric study, expected in 2023.

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 consists of two parallel treatments arms—the prophylaxis Arm A, in which patients who had received prior factor VIII prophylaxis began receiving once-weekly intravenous efanesoctocog alfa prophylaxis (50 IU/kg) 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 (50 IU/kg), then switched to once-weekly prophylaxis (50 IU/kg) for an additional 26 weeks.

Data show adults and adolescents treated with once-weekly efanesoctocog alfa experienced statistically significant and clinically meaningful improvements in physical health, pain intensity, and joint health when comparing week 52 and baseline measurements. Moreover, efanesoctocog alfa was effective at treating bleeds, including in target joints; 96.7 percent of bleeds were resolved with a single 50 IU/kg dose. Efanesoctocog alfa was well tolerated and inhibitor development to factor VIII was not detected. The most common treatment-emergent adverse events (>5 percent of participants overall) were headache, arthralgia, fall, and back pain.

“We believe transforming the treatment paradigm for hemophilia A can only be achieved through elevating standards of care towards normal hemostasis,” said Anders Ullman, head of R&D and chief medical officer of Sobi. “These data demonstrate the profile of efanesoctocog alfa in significant clinical terms, and further strengthen its potential to ultimately improve the lives of many living with this condition.”

Author: Rare Daily Staff

Stay Connected

Sign up for updates straight to your inbox.