Once-weekly Efanesoctocog Alfa Prevents Bleeds in Severe Hem A
Weekly use of the experimental, long-acting therapy efanesoctocog alfa safely and effectively prevents bleeds in adolescents and adults with severe hemophilia A, according to top-line, one-year data from the Phase 3 XTEND-1 trial.
These findings suggest that efanesoctocog alfa may be not only a more effective approach, but also a more convenient one, given its lower dosing frequency relative to currently available replacement therapies for hemophilia A.
“While advances have been made in the treatment of hemophilia, unmet medical needs still exist,” Dietmar Berger, MD, PhD, Sanofi’s global head of development, said in a press release.
“These positive top-line data, showing a very low annualized bleeding rate, enhance efanesoctocog alfa’s potential to transform hemophilia A therapy,” Berger added. “We believe efanesoctocog alfa provides higher protection for longer duration with reduced treatment burden of once-weekly dosing.”
A mainstay approach for hemophilia A, replacement therapy involves supplying patients with clotting factor VIII (FVIII), the blood clotting protein they are missing. Currently available FVIII replacement therapies, administered directly into the bloodstream, involve frequent dosing, up to three times a week, when used to prevent bleeds.
Novo Nordisk’s Esperoct (turoctocog alfa pegol) — one of the longest-acting replacement therapies currently approved for hemophilia A — requires dosing every four days for patients ages 12 and older, and twice a week for younger patients.
Efanesoctocog alfa, formerly BIVV001, delivers a version of FVIII that has been fused with fragments of other proteins (namely, von Willebrand factor and XTEN) to prolong its half-life — the time it takes for its levels in the blood to drop by half.
As such, it is expected to work longer in the body, allowing for a once-a-week dosing to effectively prevent bleeds.
Data from the previous Phase 1/2 EXTEN-A trial (NCT03205163) showed that a single dose of efanesoctocog alfa safely and effectively increased FVIII activity levels in men with severe hemophilia A. The therapy also showed a three to four times longer half-life than Takeda’s Advate, an approved FVIII replacement therapy.
These findings prompted the launch of the open-label Phase 3 XTEND-1 trial (NCT04161495), which tested efanesoctocog alfa in 159 severe hemophilia A patients, ages 12 and older, who previously received either prophylactic or on-demand FVIII replacement therapies.
Participants were given the experimental therapy either on a preventive regimen (50 international units per kilogram once weekly) for one year, or on demand at the same dose for six months, followed by a preventive regimen for the remaining six months.
Some of those on the preventive regimen throughout this study had previously participated in an observational study, called 242HA201/OBS16221, in which they received prophylaxis with currently available FVIII replacement therapies.
XTEND-1’s main goal was to assess the annualized bleeding rate (ABR) in the preventive regimen group. A key secondary goal was comparing ABRs while on efanesoctocog alfa as a preventive treatment to prior prophylaxis among those who participated in the 242HA201/OBS16221 study.
Efficacy measures for on-demand treatment, changes in joint health, physical health and function, and pain, as well as safety were also evaluated.
Top-line results showed the trial met its main goal, with one year of treatment with efanesoctocog alfa leading to a clinically meaningful reduction in ABR (mean of 0.71 bleeds over one year).
Notably, patients’ ABRs while on the experimental therapy were significantly lower than those observed with prior prophylactic FVIII replacement therapy, meeting the study’s key secondary goal.
Efanesoctocog alfa was generally well-tolerated, with the most commonly reported adverse events including headache, joint pain, and back pain. No patient developed antibodies against the delivered FVIII.
Further XTEND-1 results, including those on physical and joint health, as well as pain, are expected to be presented at future medical meetings. The data will also form the basis of planned applications to regulatory agencies seeking the therapy’s approval for hemophilia A.
“We look forward to working with regulators to bring this therapy to patients as soon as possible,” Berger said.
While approval requests are expected to start this year, a filing for the European Union is likely for 2023, after results from the ongoing Phase 3 XTEND-Kids trial (NCT04759131) become available. That study is testing the therapy in boys, up to 11 years of age, with severe hemophilia A who previously received replacement therapy.
Efanesoctocog alfa received orphan drug designations in both the U.S. and Europe, and fast track designation in the U.S. for the treatment of hemophilia A. These designations are meant to accelerate its clinical development and regulatory review.
“We believe once weekly efanesoctocog alfa has the potential to represent a new class of factor VIII therapy designed to provide high sustained factor VIII activity levels near normal for the majority of the week,” said Anders Ullman, MD, PhD, Sobi’s head of research & development and chief medical officer.