An investigational, once-weekly prophylactic treatment provided “superior bleeding prevention” as well as normal or near-normal factor VIII activity in patients with severe hemophilia A, according to a recent phase 3 study.
One injection of efanesoctocog alfa, a factor VIII therapy, resolved almost all bleeding episodes (97%) in the overall patient population and weekly prophylaxis provided mean factor VIII activity in the normal or near-normal range (>40 IU/dL) for most 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.
“Currently, [patients] often need to make trade-offs between bleed protection and dosing frequency,” study researcher Angela Weyand, MD, of Michigan Medicine, said in a press release. The current phase 3 XTEND-1 results assessing efanesoctocog alfa demonstrate that “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.”
According to the researchers, efanesoctocog alfa is also the first investigational treatment for hemophilia A to surpass the von Willebrand factor half-life ceiling, which imposes a half-life limitation on current factor VIII therapies.
The study, which was funded by drugmakers Sanofi and Sobi, was published 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 but maintaining factor VIII levels in the normal (50-150 IU/dL) or close-to-normal range (>40 to <50 IU/dL) with currently available factor VIII therapies requires frequent administration, the study authors explained.
In the phase 3, open-label 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 produce severe hemophilia A. Patients were required to have had at least 150 previous exposure days to recombinant or plasma-derived factor VIII concentrates or cryoprecipitate.
Overall, 133 patients received once-weekly prophylaxis doses of 50 IU per kg of intravenous of efanesoctocog alfa for 52 weeks (group A), and 26 patients received on-demand efanesoctocog alfa treatment for 26 weeks, followed by once-weekly prophylaxis with the medication for 26 weeks at the same 50 IU per kg dosage (group B). The primary endpoint was the mean annualized bleeding rate in group 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 0-2 bleeding episodes.
As for spontaneous bleeding, no episodes were reported in 80% of patients in group A (107 of 133) and 85% of patients (22 of 26) during the prophylaxis period in group B.
A total of 362 bleeding events occurred during the study, with most (268 of 362, or 74%) occurring in group B during the on-demand treatment period.
Among those in group A, switching from the prestudy standard of care to efanesoctocog alfa prophylaxis reduced the mean annualized bleeding rate from 2.96 to 0.69, a decrease of 77%. In group B, the mean annualized bleeding rate also decreased when patients switched from on-demand efanesoctocog alfa to prophylaxis (21.42 vs 0.69).
Scores of physical health, joint health, and pain intensity were significantly improved within the 52 weeks. In patients with target joints at baseline, 100% of the target joints were resolved after at least 12 months of continuous prophylaxis.
In other words, not only did the treatment stop bleeding, but efanesoctocog alfa also improved the overall quality of life for patients, said lead author Annette von Drygalski MD, PharmD, of University of California San Diego.
“[Efanesoctocog] alfa’s half-life and clotting factor activity levels truly translated into a number of other patient outcomes,” von Drygalski told Medscape Medical News. “All these reductions in parameters, pain improvement, improvement in joint health, reduction in pain, and of course reduction of infusions really resulted in improved quality of life for most patients, and so that’s remarkable.”
In addition, no patients developed inhibitors to factor VIII and there were no reports of serious allergic reactions, anaphylaxis, or 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 headache, arthralgia, fall, and back pain.
In an accompanying editorial, Cindy Leissinger, MD, called efanesoctocog alfa a “victory” for patients with hemophilia A.
“In a crowded field of transformative therapies for hemophilia, efanesoctocog alfa stands out as a winner — a major therapeutic advance that achieves highly protective factor VIII levels with a once-weekly infusion,” writes Leissinger, director of the Louisiana Center for Bleeding and Clotting Disorders at Tulane University School of Medicine in New Orleans.
The study was supported by Sanofi and Sobi. Both von Drygalski and Leissinger disclosed serving as consultant for Sanofi, among other disclosures. Other authors provided a range of disclosures , including serving as consultants for Sanofi and Sobi.
New Engl J Med. Published online January 26, 2023. Abstract, Editorial
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