Efanesoctocog alfa offers ‘highly efficacious protection’ to children with hemophilia A
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Key takeaways:
- Factor VIII inhibitors did not develop among children with hemophilia A treated with efanesoctocog alfa prophylaxis.
- No serious adverse events related to treatment occurred.
Efanesoctocog alfa prophylaxis exhibited high sustained factor VIII activity among younger children with severe hemophilia, according to findings published in The New England Journal of Medicine.
No factor VIII inhibitors developed in the cohort — which included children aged younger than 12 years — and approximately two-thirds of patients had no bleeding episodes, results of the phase 3 XTEND-Kids study showed.
“Once-weekly efanesoctocog alfa ... [provided] highly efficacious protection against bleeding episodes in children with severe hemophilia A, a population in which this goal has been difficult to achieve without burdensome treatment regimens,” Lynn M. Malec, MD, MSc, associate professor at Medical College of Wisconsin, and colleagues wrote. “Weekly prophylaxis with efanesoctocog alfa has the potential to provide long-term preservation of joint health.”
Background and methodology
Prophylactic coagulation factor replacement reduces bleeding episodes and improves quality-adjusted life expectancy for individuals with severe hemophilia A. However, patients who receive prophylactic treatment still are at risk for bleeding events and chronic arthropathies.
“Conventional standard half-life and extended half-life factor VIII concentrates require multiple injections weekly to manage hemophilia,” researchers wrote. “This burdensome regimen is difficult, particularly for children. Moreover, most standard and extended half-life products have shorter half-lives in children, necessitating more frequent injections, higher doses or both, which can affect treatment adherence. Until recently, once-weekly administration has not been a realistic option for highly effective factor VIII prophylaxis.”
Efanesoctocog alfa (Altuviiio, Sanofi) — a recombinant factor VIII therapy with once-weekly dosing — received FDA approval for prophylaxis and management of hemophilia A among patients 12 aged years or older based on results of the phase 3 XTEND-1 study.
Results showed once-weekly efanesoctocog alfa reduced the annualized bleeding rate by 77% compared with standard factor VIII prophylaxis for those with severe hemophilia A without inhibitors.
The phase 3 XTEND-Kids study evaluated efanesoctocog alfa in children younger than 12 years.
The open-label, international trial included children aged 6 to 11 years who received recombinant or plasma-derived factor VIII or cryoprecipitate for at least 150 exposure days, and children aged younger than 6 years who had at least 50 exposure days.
Participants received IV efanesoctocog alfa dosed at 50 IU/kg once weekly for 1 year. Researchers also used efanesoctocog alfa to treat bleeding episodes.
Researchers enrolled 74 boys (51.4% aged younger than 6 years old) and 72 completed the study.
Development of factor VIII inhibitors served as the primary endpoint. Rates of treated bleeding episodes, bleeding treatment, safety and pharmacokinetics served as secondary endpoints.
Results and next steps
No patients (0%; 95% CI, 0-5) developed factor VIII inhibitors.
Most patients (84%) experienced adverse events, but only 4% experienced adverse events related to efanesoctocog alfa.
Twelve percent of study participants developed serious adverse events but none were attributed to efanesoctocog alfa.
The most common adverse events included SARS CoV-2 positivity (15%), upper respiratory tract infection (15%) and pyrexia (12%).
No adverse events resulted in treatment discontinuation or death.
About two-thirds (64%) of patients had no treated bleeding episodes, 88% had no spontaneous bleeding episodes and 82% had no bleeding into joints. A single injection of efanesoctocog alfa resolved 95% of bleeding episodes.
Malec and colleagues reported a median annualized rate of treated bleeding episodes of 0 (interquartile range, 0-1.02), a mean overall annualized rate of treated bleeding episodes of 0.89 (95% CI, 0.56-1.42), a mean annualized rate of bleeding into joints of 0.59 (95% CI, 0.27-1.28), an annualized rate of spontaneous bleeding of 0.16 (95% CI, 0.08-0.3), and an annualized rate of traumatic bleeding of 0.44 (95% CI, 0.27-0.7).
Malec and colleagues identified the small sample size as a study limitation.
“The XTEND-ed study is currently ongoing, which will provide longer term safety and efficacy data for efanesoctocog alfa in the previously treated patients who completed the XTEND-1 or XTEND-Kids studies,” they wrote. “It should also be noted that registry studies are planned for efanesoctocog alfa in previously untreated patients with severe hemophilia A.”
There is "active discussion" about the importance of pediatric studies for rare and inherited disorders that manifest in early childhood, Pratima Chowdary, MD, MRCP, FRCPATH, professor of hemophilia and hemostasis at University College London and director of Katharine Dormandy Haemophilia & Thrombosis Centre at Royal Free Hospital in London, wrote in an accompanying editorial.
"Studies involving children are crucial for understanding their needs and responses to treatments,” Chowdary wrote. “However, conducting such studies involves ethical and practical challenges for investigators, parents and sponsors. These challenges are reflected in the choice by Malec [and colleagues] of safety, rather than efficacy, as the primary endpoint.”
In cases when the knowledge of disease biology and understanding of a drug's characteristics make it unlikely that a therapy's effect will vary across age groups, a small patient cohort can provide important insights into how age influences pharmacokinetics, Chowdary wrote.
"Indeed, there is growing interest in using postmarketing surveillance studies to complement pivotal studies involving adults,” Chowdary wrote. “This approach allows for the collection of real-world data on drug safety and efficacy in pediatric populations, without restricting access to new treatments for children."
References:
- Chowdary P. N Engl J Med. 2024;doi:10.1056/NEJMe2313795.
- Malec L, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2312611.
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Malec L, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2312611.
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