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Once-weekly prophylaxis with efanesoctocog alfa (Altuviiio) led to high sustained factor VIII activity and was effective in preventing bleeding among children with severe hemophilia A, the phase III XTEND-Kids study showed.

No factor VIII inhibitors (neutralizing antibodies against factor VIII) developed among the 74 included children, who were all boys under 12, during the course of the study, reported Lynn Malec, MD, of the Versiti Blood Research Institute in Milwaukee, and colleagues.

Among the 73 patients treated according to the protocol, treatment with the factor VIII replacement therapy resulted in a median annualized bleeding rate of 0.00 (interquartile range 0.00-1.02) and a model-based mean annualized bleeding rate of 0.61 (95% CI 0.42-0.90), they wrote in the .

Moreover, 64% of the patients had no treated bleeding episodes, 88% had no spontaneous bleeding episodes, and 82% had no episodes of bleeding into joints.

"Efanesoctocog alfa also provided effective treatment of bleeding episodes," the authors noted, with 95% of bleeding episodes resolved with one injection.

Effective protection against bleeding episodes in children with severe hemophilia A "has been difficult to achieve without burdensome treatment regimens," Malec and colleagues wrote.

"Primary prophylaxis is key to prevent bleeding into joints and subsequent hemophilic arthropathy and to maintain joint health throughout life," they observed. "In our study, prophylaxis with efanesoctocog alfa resulted in a low annualized rate of bleeding into joints. Given the effect that poor joint health can have on quality of life, early prevention of bleeding into joints may contribute to improved quality of life and greater health equity in this age group, especially over a lifetime."

In 2023, the FDA approved efanesoctocog alfa for the treatment of adults and children with hemophilia A, based on results from the phase III XTEND-1 study in which treatment with once-weekly efanesoctocog alfa resulted in a median annualized bleeding rate of 0, and reduced the annualized mean bleeding rate by 77%, compared with treatment with a standard-care factor VIII prophylaxis regimen. The approval was also based on interim data from XTEND-Kids.

While cautioning that results across trials can't be directly compared because of different patient populations and trial designs, Malec and colleagues noted that the results from XTEND-Kids showed "favorable bleeding protection" versus other half-life factor VIII products, such as damoctocog alfa pegol evaluated in the study, , and efmoroctocog alfa evaluated in the study.

In an accompanying , Pratima Chowdary, MD, of the Royal Free Hospital in London, said that the study comes with the limitation that only those with prior exposure to factor VIII and without inhibitors were enrolled in the trial, thus only including patients with pre-existing tolerance of factor VIII.

"As such, immunogenicity needs to be assessed in other patients, especially those with no previous treatment with factor VIII," she wrote.

Chowdary also addressed the issue of conducting pediatric studies in rare diseases, noting that this involves a number of ethical and practical challenges, which are reflected in the choice of safety, rather than efficacy, as the primary endpoint in this study.

"If the effect of a drug is unlikely to vary across age groups (given knowledge of the biologic features of the disease and the characteristics of the drug), a relatively small patient cohort can provide information on the influence of age on pharmacokinetics," she added. "There is growing interest in using postmarketing surveillance studies to complement pivotal studies involving adults. 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."

was an open-label, international, single-group study involving 74 previously treated boys younger than 12 years with severe hemophilia A. Of these patients, 73 had received prophylaxis before the start of the study, with most using extended half-life products. Median patient age was 5 years, 74% were white, 11% were Asian, and 4% were Black.

Patients were assigned to receive once-weekly prophylactic doses of intravenous efanesoctocog alfa (50 IU/kg of body weight) for 52 weeks, and bleeding episodes were treated with one dose of efanesoctocog alfa, with additional doses of 30 or 50 IU/kg every 2 or 3 days if the episode did not resolve.

The overall median number of exposure days to efanesoctocog alfa was 53, and 89% of patients had at least 50 exposure days.

Malec and colleagues also assessed quality of life using the Haemophilia Quality of Life Questionnaire for Children total score (ranging from 0 to 100, with lower scores indicating better quality of life), and found that the mean change in the total score from baseline to week 52 was -2.5 in 14 patients with available data -- a trend in the direction of an improvement in quality of life.

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