An investigational prophylactic treatment once a week provided “superior bleeding prevention” as well as normal or near normal treatment. factor viii activity in patients with hemophilia Aaccording to a recent phase 3 study.
One injection of efanesoctocog alfa, a factor VIII therapy, resolved nearly all bleeding episodes (97%) in the general patient population, and weekly prophylaxis provided mean factor VIII activity in the normal or near-normal range (>40 IU /dL) for most cases. of the week.
Efanesoctocog alfa is currently under priority review by the US Food and Drug Administration (FDA) and the target action date for the approval decision is next Tuesday, February 28.
“At the moment, [patients] trade-offs often need to be made between protection against bleeding and frequency of dosing,” study investigator Angela Weyand, MD, of Michigan Medicine, said in a press release. The current phase 3 results of XTEND-1 evaluating efanesoctocog alfa demonstrate that “we have the opportunity to provide near normal factor activity levels over a prolonged period (mostly one week) with a single dose, which is the first for hemophilia A.”
According to the researchers, efanesoctocog alfa is also the first investigational treatment for hemophilia A to exceed the von Willebrand factor half-life ceiling, which imposes a half-life limitation on current factor VIII therapies.
The study, which was funded by the pharmaceutical companies Sanofi and Sobi, was posted online last month in the New England Journal of Medicine.
Hemophilia A is a rare genetic disorder caused by a lack of blood clotting factor VIII. Normalizing factor VIII levels can help protect patients from spontaneous and traumatic bleeding, while maintaining factor VIII levels at normal levels (50-150 IU/dL) or near the -normal range (>40 to <50 IU/dL) with currently available factor VIII therapies requires frequent administration, the study authors explained.
In the open-label Phase 3 trial, the authors evaluated the efficacy, safety, and pharmacokinetics of efanesoctocog alfa for routine prophylaxis, treatment of bleeding episodes, and perioperative management in previously treated patients with severe hemophilia A.
Patients were 12 years of age or older with endogenous factor VIII activity of less than 1 IU/dL or a genotype known to cause severe hemophilia A. Patients must have had at least 150 days of prior exposure to recombinant or plasma-derived factor VIII. concentrates or cryoprecipitate.
In total, 133 patients received once-weekly prophylaxis doses of 50 IU/kg intravenous efanesoctocog alfa for 52 weeks (Arm A), and 26 patients received efanesoctocog alfa as-needed treatment for 26 weeks, followed by once-a-week prophylaxis. week with the medication for 26 weeks at the same dose of 50 IU per kg (group B). The primary endpoint was the mean annualized bleeding rate in arm A.
Among those in group A, the annualized bleeding rate was 0 (interquartile range 0-1.04) and the estimated mean annualized bleeding rate was 0.71. Overall, 65% of these patients (86 of 133) had no bleeding episodes and 93% had between 0 and 2 bleeding episodes.
Regarding spontaneous bleeding, no episodes were reported in 80% of patients in group A (107 of 133) and in 85% of patients (22 of 26) during the prophylaxis period in group B.
A total of 362 bleeding events occurred during the study, with the majority (268 of 362 or 74%) occurring in Arm B during the on-demand treatment period.
Among those in Arm A, switching from pre-study standard of care to efanesoctocog alfa prophylaxis reduced the mean annualized bleeding rate from 2.96 to 0.69, a 77% decrease. In arm B, the mean annualized bleeding rate also decreased when patients switched from efanesoctocog alfa to on-demand to prophylaxis (21.42 vs. 0.69).
Physical health, joint health, and pain intensity scores improved significantly within 52 weeks. In patients with baseline target joints, 100% of target joints resolved after at least 12 months of continuous prophylaxis.
In other words, the treatment not only stopped the bleeding, but efanesoctocog alfa also improved the patients’ overall quality of life, said lead author Annette von Drygalski, MD, PharmD, of the University of California, San Diego.
“[Efanesoctocog] Clotting factor activity levels and alpha half-life really translated into a number of other patient outcomes,” Drygalski said. Medscape Medical News. “All of these reductions in parameters, the improvement in pain, the improvement in joint health, the reduction in pain, and of course the reduction in infusions really did result in better quality of life for most of the patients.” patients, and that’s extraordinary.
Furthermore, no patients developed factor VIII inhibitors and there were no reports of serious allergic reactions, anaphylaxisor vascular thrombotic events.
Of the 159 patients who received at least one dose of efanesoctocog alfa, 123 (77%) had at least one adverse event that developed or worsened during the treatment period. The most common adverse events were headachecase of arthralgia and Back pain.
in it accompanying editorialCindy Leissinger, MD, called efanesoctocog alfa a “win” for hemophilia A patients.
“In a crowded field of transformative therapies for hemophilia, efanesoctocog alfa stands out as a winner: a therapeutic breakthrough that achieves highly protective levels of factor VIII with a once-weekly infusion,” writes Leissinger, director of the Louisiana Center. for bleeding and coagulation. at the Tulane University School of Medicine in New Orleans.
The study was supported by Sanofi and Sobi. Both by Drygalski and Leissinger revealed service as a consultant to Sanofi, among other revelations. Other authors provided a variety of revelations including providing services as consultants to Sanofi and Sobi.
New English J Med. Published online on January 26, 2023. summaries, Editorial
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