Altuviiio prevents bleeds in young children with severe hem A: Trial
64% of those treated weekly in Phase 3 study had no bleeds, 82% no joint bleeds
Nearly two-thirds of children with severe hemophilia A on preventive, or prophylactic, treatment with once-weekly Altuviiio (efanesoctocog alfa) in the yearlong XTEND-Kids study were free of bleeding episodes needing treatment.
More than 80% in this Phase 3 clinical trial also were free of spontaneous bleedings and joint bleeds needing treatment. Joint bleeds, a common issue in hemophilia A, can contribute to joint problems.
Full trial results were published in The New England Journal of Medicine in the study, “Efanesoctocog Alfa Prophylaxis for Children with Severe Hemophilia A.” Full data also were added to prescribing information for Altuviiio.
“Offering a treatment option that emphasizes effective bleed protection in children with hemophilia can help give families increased peace of mind when their loved ones participate in everyday activities,” Dietmar Berger, MD, PhD, global head of development and chief medical officer at Sanofi, the therapy’s developer along with Sobi, said in a company press release.
Altuviiio is a FVIII replacement therapy for people with hemophilia A
“Children represent a population for which it has been historically difficult to achieve effective bleed prevention and these published results demonstrate an important breakthrough as we strive to optimize the standard of care,” added Lynn Malec, MD, the study’s first author and an associate professor of medicine and pediatrics at the Medical College of Wisconsin.
Hemophilia A is caused by mutations that lead to reduced activity of the clotting protein factor VIII (FVIII). Altuviiio is a FVIII replacement therapy that works to deliver a version of this protein that remains in the body three to four times longer than standard and extended half-life FVIII products, Sanofi reports.
It’s approved in the U.S. as both a prophylactic and on-demand treatment for hemophilia A patients of all ages. As prophylaxis, Altuviiio is given by injection once weekly, which can be done at home with appropriate training.
The Phase 3 XTEND-Kids trial (NCT04759131) enrolled 74 previously treated boys, all younger than age 12 and with severe hemophilia A, defined as FVIII activity less than 1% of normal. None had a history of inhibitors, or antibodies that neutralize FVIII-based therapies and reduce their efficacy.
Participants received once-weekly injections of Altuviiio for 52 weeks, and the study’s main goal was to see if any of them would develop inhibitors.
All but two boys completed the study — one was pulled at the trial’s start after he was found to have pre-existing inhibitors, and another left midway through due to an extreme fear of blood draws.
Children younger than age 12 showed improving joint health across trial’s year
As previously announced by Sanofi, the study met its main goal: None of the boys developed inhibitors after a year on Altuviiio. In addition, the once-weekly prophylactic was well tolerated, with no treatment-related serious adverse events reported.
In terms of secondary goals, data showed that the median annualized rate of bleeds requiring treatment was zero, with nearly two-thirds of patients (64%) experienced no such bleeds. The therapy also was effective at preventing treated bleeds across types and locations: 88% of the boys experienced no spontaneous bleeds, and 82% had no joint bleeds.
Consistently, average measures of joint health improved over the course of the study, as did measures of life quality.
For boys with bleeds requiring treatment, almost all bleeding episodes were resolved with a single dose of on-demand Altuviiio. Two boys underwent a major surgery during the study, and a single Altuviiio dose effectively controlled bleeds during the procedures.
Potential to ease treatment burden felt by people with severe hemophilia
Available pharmacological data indicated that FVIII average activity was in the normal to near-normal range for up to three days after Altuviiio injection. FVIII activity remained above 10% of normal — within the range for what’s considered mild hemophilia A — for nearly a week following each injection.
“Shortening the weekly administration interval was not deemed to be necessary in any patient during this study,” the researchers wrote.
Malec said that “achieving high-sustained factor activity with once-weekly dosing helps mitigate the need to make a tradeoff between the treatment burden of factor replacement therapy and efficacy, which we often witness in treating severe hemophilia.”
Study findings, overall, show that Altuviiio “provided high sustained factor VIII activity and highly efficacious protection against bleeding episodes in children with severe hemophilia A,” the researchers wrote.
They also noted that XTEND-Kids results are consistent with those from the Phase 3 XTEND-1 trial (NCT04161495), showing that about two-thirds of severe hemophilia A patients, ages 12 and older, were bleed-free on Altuviiio.
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