Efanesoctocog Alfa Reduces Bleeding, Pain in Phase 3 Study

FDA's decision on the hemophilia A treatment expected by end of February

Marisa Wexler, MS avatar

by Marisa Wexler, MS |

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Most people with severe hemophilia A who were given once-weekly treatment with efanesoctocog alfa in the Phase 3 XTEND-1 trial were bleed-free over a year on treatment.

The therapy also improved joint and overall physical health and eased pain intensity in the participants compared with previous treatments.

Results from the trial form the basis for Sobi and Sanofi’s application to the U.S. Food and Drug Administration seeking the approval of efanesoctocog alfa for hemophilia A. The agency’s decision is expected by the end of February. If the therapy is approved, it’s expected to be marketed under the brand name Altuviiio in the U.S.

“We are steadfast in our commitment to developing novel treatment options that have a meaningful impact for patients,” Dietmar Berger, MD, PhD, Sanofi’s global head of development and chief medical officer, said in a press release. “We are hopeful that Altuviiio (efanesoctocog alfa) will help deliver on this goal by offering unprecedented factor activity levels with once-weekly dosing, fulfilling its potential as a best-in-class therapy for hemophilia A.”

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Full XTEND-1 trial data show treatment can offer increased bleed protection

Top-line data from XTEND-1 was announced last year. Full results have now been reported in the study “Efanesoctocog Alfa Prophylaxis for Patients with Severe Hemophilia A,” which was published in The New England Journal of Medicine.

Hemophilia A is caused by low levels of a clotting protein called factor VIII (FVIII). Replacement therapies, where a version of this clotting protein is administered as treatment, are standard of care.

Although numerous replacement therapies for hemophilia A are available, they generally require frequent dosing. That’s because FVIII is normally stabilized by another protein called von Willebrand factor (VWF), which is recycled rather rapidly in the bloodstream. This has posed a “ceiling” effect on how long-lasting replacement therapies can be.

Efanesoctocog alfa (formerly known as BIVV001) contains a version of FVIII that is attached to a portion of the VWF protein and another one called XTEN. Its design is specifically intended to stabilize the clotting factor and overcome the VWF “ceiling effect,” allowing for less frequent dosing.

The Phase 3 XTEND-1 trial (NCT04161495) tested the safety and efficacy of efanesoctocog alfa in 159 people with severe hemophilia A, recruited at 48 centers across 19 countries.

All the patients were assessed by the physician as having an excellent or effective response to efanesoctocog alfa.

All patients on previous FVIII replacement therapies before entering study

The study included patients 12 and older; participants had a mean age of 35 years. Most participants (over 60%) where white, and all but one were male. All of the patients had previously been on treatment with other FVIII replacement therapies before entering the study.

Most patients (a total of 133) were given prophylactic (preventive) treatment with efanesoctocog alfa, which was administered into the bloodstream once weekly. A smaller group of 26 patients instead used efanesoctocog alfa as an on-demand treatment for bleeds. The choice of prophylactic versus on-demand treatment in the trial was based on the type of treatments that patients had been on previously.

In the prophylactic group, nearly two-thirds (65%) of evaluable patients had no recorded bleeds over the course of one year of treatment. The vast majority (93%) in this group had less than three bleeds during the study, and 80% had no spontaneous bleeds (i.e., bleeding without an obvious cause, like an injury).

“All the patients were assessed by the physician as having an excellent or effective response to efanesoctocog alfa,” the researchers wrote.

The overall mean annualized bleeding rate on efanesoctocog alfa prophylaxis was 0.69 bleeds per year — a statistically significant 77% reduction from the rate seen while patients were on their previous treatment, which was nearly three bleeds per year.

Measures of life quality, pain, and joint health also showed significant improvements with efanesoctocog alfa compared with prior treatments.

“The data show that efanesoctocog alfa can offer patients increased bleed protection, leading to improved outcomes, such as reduced pain and improved physical functioning, that may impact daily life with a reduced treatment burden,” said Angela Weyand, MD, a professor at the University of Michigan and co-author of the study.

Pharmacological data showed that mean FVIII activity was higher than 40 international units per deciliter (IU/dL) for four days following each weekly dose of efanesoctocog alfa. By the seventh day after dosing, mean FVIII activity was at 15 IU/dL. For context, people without hemophilia usually have FVIII activity levels from 50 to 150 IU/dL.

“Based on the XTEND-1 study results assessing efanesoctocog alfa, we have the opportunity to provide near normal factor activity levels for an extended period of time (the majority of a week) with a single dose, which is a first for hemophilia A,” Weyand said.

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On-demand treatment resolved nearly all bleeding events

In the patients given on-demand treatment, a single injection of efanesoctocog alfa effectively resolved nearly all (97%) bleeding events that occurred.

Over the course of the study, 12 participants underwent surgery while on efanesoctocog alfa. In all of them, bleeding control was deemed excellent by the treating clinicians.

“Collectively, these results suggest the prophylaxis with efanesoctocog alfa has the potential to provide meaningful improvements in physical health and pain for persons with severe hemophilia A,” the researchers wrote.

Treatment with efanesoctocog alfa was overall well-tolerated in this study. The most common side effects included headache, joint pain, falls, and back pain. There was one death during the study due to cancer, which was deemed to be unrelated to treatment. None of the patients developed inhibitors — neutralizing antibodies against efanesoctocog alfa that can lower the treatment’s efficacy.

“The majority of [side effects] were mild in degree and did not result in discontinuation of efanesoctocog alfa,” the researchers wrote, noting no serious allergic reactions or clotting events were observed.

In an editorial published alongside the study, Cindy Leissinger, MD, director of the Louisiana Center for Bleeding and Clotting Disorders, said the trial results suggest efanesoctocog alfa “stands out as a winner” among hemophilia treatments, representing “a major therapeutic advance that achieves highly protective factor VIII levels with a once-weekly infusion.”