Efanesoctocog alfa, formerly known as BIVV001, is an investigational and longer-lasting factor VIII (FVIII) replacement therapy for people with hemophilia A.
Efanesoctocog alfa aims to be more effective and convenient than currently available replacement therapies for hemophilia A. It has shown efficacy in clinical trials with preventive (prophylaxis) dosing at once-weekly intervals.
How does efanesoctocog alfa work?
Efanesoctocog alfa is based on Fc fusion technology, and is made by adding a region of a blood-clotting protein called von Willebrand factor (VWF) and a polypeptide called XTEN to a recombinant, or man-made, FVIII-Fc fusion protein. These additions were made to extend the therapy’s half-life — the time it takes for its levels in the blood to drop by half — allowing it to work longer in the body so that once-a-week dosing would effectively prevent bleeds.
It is reported to be the first molecule of its kind to fuse together four different proteins: FVIII, VWF, XTEN, and Fc.
Efanesoctocog alfa in preclinical studies
In preclinical studies, the pharmacological properties of efanesoctocog alfa were found to be similar to those of recombinant FVIII (rFVIII). The experimental therapy also extended the half-life of FVIII in mouse models of hemophilia A to four times beyond that achieved with conventional FVIII. The half-life of intravenously (into-the-vein) administered efanesoctocog alfa was about 37 hours.
In addition, animals given a low dose — 25 international units per kg of body weight (IU/kg) — of efanesoctocog alfa retained 5% of normal FVIII activity after 120 hours. This indicated a potential for full protection from spontaneous bleeding in this animal model.
Efanesoctocog alfa in clinical trials
An open-label (no placebo group), dose-escalation Phase 1/2a study, called EXTEN-A (NCT03205163), investigated the safety, tolerability, and pharmacokinetics (movement of a substance into, through, and out of the body) of a single dose of efanesoctocog alfa injected into the bloodstream of men with severe hemophilia type A, whose FVIII activity levels were less than 1% of normal.
Enrolled patients were first given a single dose of Advate, an approved FVIII replacement therapy, at a dose of 25 IU/kg or 65 IU/kg. After a three-day washout, they then received efanesoctocog alfa at the same dose.
Trial results showed a single dose of efanesoctocog alfa to safely and effectively increase FVIII activity levels in these men, with a three to four times longer half-life than Takeda’s Advate. The therapy was generally well-tolerated, with no allergic reactions or clinically significant treatment-related adverse events observed.
A Phase 3, open-label clinical trial (NCT04161495), called XTEND-1, followed. It tested efanesoctocog alfa in 159 severe hemophilia A patients, ages 12 and older, previously given either prophylactic or on-demand FVIII replacement therapies.
Enrolled patients received the experimental therapy on a preventive regimen at 50 IU/kg for one year, or as an on-demand treatment at the same dose for six months, followed by a preventive regimen for the remaining six months.
Top-line XTEND-1 results, reported in March 2022, showed the trial met its primary goal. A clinically meaningful reduction in annualized bleeding rate (ABR) — a mean ABR of 0.71 — was reported in those on preventive treatment for one year. A number of these patients, followed while using other FVIII replacement therapies in a separate study, also showed significantly lower ABRs with efanesoctocog alfa than what had been observed in that earlier study, meeting a key secondary trial goal.
Efanesoctocog alfa was generally well-tolerated, with the most commonly reported side effects including headache, joint pain, and back pain. No one developed antibodies against the delivered FVIII.
Another open-label Phase 3 trial, called XTEND-Kids (NCT04759131), is evaluating the development of inhibitors — neutralizing antibodies against FVIII — over the course of one year of weekly efanesoctocog alfa in up to 65 previously treated boys, all younger than 12, with severe hemophilia A. Treatment safety and efficacy in reducing spontaneous and traumatic bleeding episodes, as well as the therapy’s pharmacological properties, are also being evaluated.
Participants in this global trial, due to concluded in February 2023, will have the option to enter an extension phase to continue the treatment.
Sanofi and Sofi announced plans to begin filing applications to regulatory agencies in 2022 requesting that efanesoctocog alfa be approved to treat hemophilia A. A request to European Union regulators will wait until the following year, when XTEND-Kids trial data are available.
The FDA designated efanesoctocog alfa an orphan drug in August 2017, and the European Commission followed suit in June 2019. The therapy was also granted fast track designation by the FDA in February 2021. This designation is given to speed the development and review of therapies that treat severe or life-threatening disorders with clear unmet clinical needs.
Last updated: March 14, 2022
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