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Turoctocog alfa prevented, treated bleeds in previously untreated pediatric patients with severe hemophilia A



The recombinant factor VIII turoctocog alfa effectively prevented and stopped bleeds among previously untreated children with hemophilia A enrolled in a multicenter trial, investigators have reported.

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Nearly 86% of patients who developed inhibitors and started immune tolerance induction with turoctocog alfa went on to have a negative inhibitor titer, according to investigators in guardian 4, an international, nonrandomized, phase 3 trial.

The treatment was well tolerated in these pediatric patients, and the rate of inhibitor development in the study was “within the expected range” for previously untreated patients with severe hemophilia A, wrote the investigators, led by Hassan M. Yaish, MD, of the University of Utah, Salt Lake City.

Turoctocog alfa, a recombinant, B domain–truncated human coagulation factor VIII (FVIII), is known to be safe and effective in previously treated patients with hemophilia A based on results of the guardian 1, 2, and 3 clinical trials, according to Dr. Yaish and coauthors.

“This is the first trial within the guardian clinical trial program to evaluate turoctocog alfa in previously untreated patients, a patient population that is generally at an increased risk of developing antibodies to foreign protein such as exogenous FVIII,” wrote Dr. Yaish and coauthors in their report on guardian 4, which appears in Haemophilia.

The guardian 4 trial included a total of 60 patients aged less than 6 years with severe hemophilia A treated at 1 of 40 sites internationally, including the United States. The investigators noted that 58 of those patients received turoctocog alfa as prophylaxis, and 49 completed the study.

The primary endpoint of the study was the incidence of FVIII inhibitors within the first 50 exposure days, the time period during which inhibitors most frequently occur, investigators wrote.

In all, 25 of the 58 prophylactically treated patients (43.1%) developed FVIII inhibitors in that period, according to Dr. Yaish and colleagues.

The inhibitor incidence rate for other recombinant FVIII products in key studies of previously untreated patients range from 24.4% to 44.5%, they wrote in a discussion of that result.

In the present study, guardian 4, the estimated mean annualized bleed rate was 4.26 bleeds per patient per year, the investigators also reported.

The success rate for treatment of bleeds during prophylaxis was 88.5%. Of 402 bleeds, 227 (56.5%) were controlled with a single injection of turoctocog alfa, according to the report, while 22.6% and 7.5% were controlled with two and three injections, respectively.

Of 21 patients with inhibitors who started immune tolerance induction with turoctocog alfa, 18 (85.7%) had a negative inhibitor titer at the end of the trial, while treatment was withdrawn in 3 (14.3%) because insufficient decline in titer or persistent positivity for titers following 2 years of the therapy, according to the report.

Novo Nordisk sponsored the guardian 4 study. Dr. Yaish reported disclosures related to Novo Nordisk, Shire, Bayer, and Octapharma.

SOURCE: Yaish HM et al. Haemophilia. 2019 Dec 9. doi: 10.1111/hae.13883.

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