A hereditary disease, hemophilia A is characterized by a deficiency of the blood protein factor VIII (FVIII), which is essential for the formation of blood clots. Many patients receive FVIII infusions to replace the protein their blood lacks; however, these treatments have notoriously short half-lives, requiring patients to re-infuse frequently to prevent spontaneous bleeds.

“Although we have seen significant innovation in the hemophilia treatment space in the last decade, there is a need for patients to have access to therapies that will optimally protect them from joint and other bleeding events throughout their lifetimes, while also minimizing the burden of treatment,” Dr. Malec said. “The burden of hemophilia and hemophilia treatment is not just physical, but also psychological for patients and caregivers. As a doctor who specializes in hemophilia and bleeding disorder care for patients of all ages and who focuses on clinical research, I’m routinely reminded of the ongoing challenges that those I care for face. Participating in research allows us, as a community of clinicians and patients, to not settle for anything less than the aspirational goal of optimized health for those with hemophilia.”

The advent of new treatments

Over the years, researchers have worked hard to develop new treatments that improve the daily lives of patients with hemophilia. They already knew that high, sustained factor levels improved patients’ protection from bleeds and preserved joint health; however, despite therapeutic advances, patients with severe hemophilia A still experienced bleeds, impacting their physical health and quality of life.

In February 2023, the Food and Drug Administration (FDA) approved efanesoctocog alfa, a prophylactic drug used to reduce the number of bleeding episodes in adult males with severe hemophilia A. In the clinical trial, researchers found that the drug maintained FVIII levels with a normal to near-normal range for most of the week in adults and adolescents over age 12. However, it was unknown how patients under age 12 would respond to the medication.

Groundbreaking clinical trial

The international pediatric clinical trial of efanesoctocog alfa, XTEND-Kids, included children under age 12 with severe hemophilia A who previously received treatment with another FVIII infusion therapy. Researchers sought to determine whether efanesoctocog alfa was safe for bleed prevention in children under 12, if these patients developed antibodies to efanesoctocog alfa, and if the antibodies impacted the drug’s efficacy.

Versiti Comprehensive Center for Bleeding Disorders (CCBD), a federally designated hemophilia treatment center (HTC), had the highest number of patients enrolled in the study. Over the course of 52 weeks, 73 of the 74 clinical trial participants received once-weekly injections of efanesoctocog alfa, while one patient received two or three injections per week as part of an intensified consolidation treatment. At the conclusion of the year-long trial, researchers found no evidence of neutralizing antibodies to FVIII, inhibitors or anti-drug antibodies, indicating that taking efanesoctocog alfa weekly is a highly effective treatment for protecting children with hemophilia A against bleeding. Furthermore, they found that FVIII levels remained in the normal to near-normal range for up to three days after dosing and noted high sustained FVIII activity throughout weekly dosing intervals.

Ultimately, efanesoctocog alfa was well-tolerated by clinical trial participants and outcomes were consistent with the adult clinical trial, making efanesoctocog alfa a first-in-class, high-sustained FVIII therapy that allows children and adults with hemophilia A to replace deficient FVIII therapies with a once-weekly injection.

Quality of life improvements

Caregivers of the patients enrolled in the clinical trial reported 100% satisfaction after switching to efanesoctocog alfa, and that those children experienced less pain and showed improvements in their quality of life. One caregiver said, “We are very satisfied, because he only has to take it once a week, and he doesn’t have any more superficial bruising, and he hasn’t had any joint bleeds and any trouble walking around since he started to use this new medication, and it’s long-lasting.”

“The end-of-study exit interview that was offered to the caregivers of all subjects enrolled in the study provided some of the most important information, in my mind, about the study,” Dr. Malec said. “It showed that the moms, dads or caregivers of the patients in the study found it to be not only effective in preventing bleeding, but in what truly matters for kids with hemophilia, had improved quality of life beyond the data that I would typically collect as part of my follow-up with a patient and their family.”

Versiti’s expertise in blood and bleeding disorders

Participation in this clinical trial marks a full-circle moment for Versiti CCBD, a top-class hemophilia treatment center that counts both a clinical team and research team among its staff. “My patients who were enrolled in the study all chose to continue to receive the therapy after the conclusion of the XTEND-Kids study, initially by enrollment in another clinical study (XTEND-ED), and now by receiving this medication as a prescription,” Dr. Malec said. “Offering this study to patients at Versiti, and now the availability of this prescribable medication to patients at CCBD, furthers my ability to offer patients state-of-the-art care. As I partner with patients and families to make treatment decisions, having medications such as efanesoctocog alfa strengthens my ability to offer options that can contribute to more optimized health. It makes all the hard work of being a site participating in the study worth the effort.”

Thanks to Versiti CCBD and its patients who enrolled in the clinical trial, the FDA received the data it needed to approve efanesoctocog alfa for treatment of children with severe hemophilia A. The drug is now commercially available, and all of the young boys who enrolled in the clinical trial now take efanesoctocog regularly and were rolled over into the XTEND-ED study.

“I was recruited to Versiti in 2016 to direct research at CCBD and to become one of the core physicians caring for patients with hemophilia, rare bleeding disorders and other hematologic conditions across the lifespan,” Dr. Malec said. “Having trained in Pittsburgh, I was aware of the great work done at Versiti Blood Research Institute; the legacy of expert care provided by its founders, Drs. Bob Montgomery and Joan Gill; and the important niche lab offerings in the Hemostasis Lab, led by Dr. Ken Friedman and others. I wanted to further my impact as a doctor and a researcher and was drawn to the opportunities at Versiti. Now, nearly eight years later, I love that I have great continuity with patients—in one clinic, I may see a newborn baby and an 80-year-old with hemophilia—while also contributing to scientific and therapeutic advances that positively impact individuals beyond those who I see in my own clinic.”

Read the full paper in the New England Journal of Medicine.

About the expert: Lynn Malec, MD, MSc, is the medical director at Versiti Comprehensive Center for Bleeding Disorders; associate investigator at Versiti Blood Research Institute; senior director at Versiti Medical Sciences Institute; and associate professor of medicine and pediatrics, Division of Hematology/Oncology, at the Medical College of Wisconsin.