Weekly Efanesoctocog Alfa Leads to Clinical Benefits in Hem A Study

Experimental replacement therapy found to improve physical and joint health

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Weekly use of the experimental therapy efanesoctocog alfa maintains therapeutic levels of factor VIII (FVIII) — the missing clotting factor in hemophilia A — and significantly improves physical and joint health, while reducing pain, in adolescents and adults with a severe form of the disease.

These are the additional one-year findings of the Phase 3 XTEND-1 trial (NCT04161495), whose previously announced results showed the therapy effectively prevented bleeds in these patients and to a greater extent than previous preventive, or prophylactic, therapies.

The new findings further support efanesoctocog alfa as a potentially more effective and convenient approach — due to its lower dosing frequency compared with currently available replacement therapies for hemophilia A.

“The Phase 3 data demonstrate once-weekly efanesoctocog alfa’s potential to provide superior bleed protection, leading to substantial improvements in physical health, pain and joint health, by sustaining high factor levels for the majority of the week,” Annette von Drygalski, MD, the director of the University of California San Diego’s Hemophilia and Thrombosis Treatment Center, said in a press release from Sanofi and Sobi, which are jointly developing the therapy.

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What’s the significance of updated one-year results?

“These unprecedented results may offer people with hemophilia A the possibility to redefine their treatment expectations,” added von Drygalski, who is also a researcher and professor of medicine at the university.

The updated results were shared in a late-breaking session at the 2022 International Society on Thrombosis and Haemostasis Congress, held July 9–13, in London and online. The oral presentation was titled “Efficacy, Safety, and Pharmacokinetics of Once-Weekly Efanesoctocog Alfa (BIVV001) Prophylaxis in Previously Treated Patients With Severe Hemophilia A: Results From the Phase 3 XTEND-1 Study.”

XTEND-1 data supported Sanofi and Sobi’s filing of an application seeking the approval of efanesoctocog alfa in the U.S. last month. A similar submission in the European Union is expected in 2023, after results come in from the Phase 3 XTEND-Kids study (NCT04759131), which is testing the therapy in boys with severe hemophilia A.

“We are committed to advancing innovative medicines that disrupt the status-quo and address the unmet needs that persist for people with rare conditions like hemophilia,” said Dietmar Berger, MD, PhD, Sanofi’s global head of development and chief medical officer.

“These robust data illustrate the promise of efanesoctocog alfa’s efficacy with once-weekly dosing and underscore its potential as a therapy with best-in-disease efficacy,” Berger added.

Replacement therapy, a mainstay treatment for hemophilia A, supplies patients with FVIII — the blood clotting protein they are missing. When used to prevent bleeds, currently available FVIII replacement therapies, administered directly into the bloodstream, require frequent dosing, up to three times a week.

Efanesoctocog alfa, formerly known as BIVV001, delivers a version of FVIII that has been fused with fragments of other proteins to increase its stability, protecting it from degradation. As such, it is expected to work longer in the body, allowing for a once-a-week dosing to effectively prevent bleeds.

What’s the goal of the Phase 3 XTEND-1 study?

The open-label Phase 3 XTEND-1 study evaluated efanesoctocog alfa’s safety, pharmacokinetics (movement into, through, and out of the body), and effectiveness in 159 adults and adolescents, 12 and older, with severe hemophilia A. All had previously received either prophylactic or on-demand FVIII replacement therapies.

A total of 132 males and one female were given 50 international units (IU) of the therapy per kilogram of body weight once weekly (preventive regimen) for one year. The remaining 26 patients, all males, received the therapy on demand, at the same dose, for six months, followed by a preventive regimen for an additional six months.

Previous top-line, one-year results showed the trial met its main goal, with once-weekly treatment with efanesoctocog alfa effectively lowering the frequency of bleeding events over one year (mean of 0.71 bleeds).

In 78 patients with pre-trial bleeding data, efanesoctocog alfa was associated with a 77% drop in the annualized bleeding rate relative to prior prophylactic FVIII therapy (mean of 0.69 vs. 2.96 bleeds), meeting the study’s key secondary goal.

Newly presented data showed that once-weekly efanesoctocog alfa was able to maintain FVIII levels in the normal to near-normal range (higher than 40% of normal) for most of the week, dropping to 15% of normal at the seventh day post-dosing.

Patients given the preventive regimen for one year also experienced significant and clinically meaningful improvements in physical and joint health, and reductions in pain intensity.

Moreover, on-demand efanesoctocog alfa was effective at treating bleeds, including in target joints, with 96.7% of them being resolved with a single dose.

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The long-lasting therapy was generally well-tolerated, with the most common adverse events being headache, joint pain, fall, and back pain. No antibodies against the delivered FVIII were detected.

“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,” said Anders Ullman, MD, PhD, Sobi’s head of research and development and chief medical officer.

Efanesoctocog alfa received orphan drug designations in the U.S. and Europe, and fast track and breakthrough therapy designations in the U.S. for hemophilia A. These designations are meant to expedite the therapy’s clinical development and regulatory review.