Transition to Hemlibra Safe, Effective in Children With Hemophilia A
Treatment was also safe in children who'd been minimally treated or not at all
Switching to Hemlibra (emicizumab) was safe and effective in children with hemophilia A, including in those who had been minimally treated before or who had not been treated at all, a real-world study reported.
Researchers noted that studies involving a larger number of patients are still warranted to validate “treatment decision making on [previously untreated patients/minimally treated patients].”
The study, “Emicizumab in children: bleeding episodes and outcome before and after transition to Emicizumab,” was published in BMC Pediatrics.
Hemlibra, marketed by Genentech, is an antibody-based therapy designed to mimic the activity of factor VIII (FVIII), the clotting protein that’s faulty in people with hemophilia A.
The treatment, given by an under-the-skin (subcutaneous) injection, is approved for hemophilia A patients with or without FVIII inhibitors — neutralizing antibodies that might make standard replacement therapies ineffective.
Several clinical trials in adults and children report Hemlibra markedly reduced the annual bleeding rate (ABR) and has a good safety profile. However, there is a lack of real-world studies of it in children with hemophilia A, particularly in those previously untreated and minimally treated.
Children’s outcomes with hemophilia A
Scientists from the University of Freiburg, Germany studied the outcomes of 13 children with hemophilia A before and after treatment with Hemlibra.
All but one of the children had severe hemophilia A. Participants had a median age of 5.3 (range: 0.26–17.5) at the time the treatment was initiated.
Two children were previously untreated and one was minimally treated (less than five exposure days to FVIII). The remaining patients were treated prophylactically, or on a preventive basis, with FVIII-substitution before starting Hemlibra. Three patients with inhibitors underwent a minor surgery.
Children were initially given four weekly doses of Hemlibra at 3 mg/kg, followed by a maintenance dose of 1.5 mg/kg once every week. Treatment levels were assessed after three doses of 3 mg/kg and at every follow-up appointment with the maintenance dose. Median follow-up time on Hemlibra was nearly 24 months (two years).
Patients without inhibitors who had bleeds while on Hemlibra remained on FVIII substitution. Those with inhibitors who had a surgery were recommended to use Hemlibra along with a recombinant (man-made) factor seven a (rFVIIa) before and after the procedure.
The study assessed ABR, including total ABR, spontaneous ABR, traumatic ABR, and joint ABR, before and after switching to Hemlibra.
FVIII inhibitors also were frequently measured during treatment. The activated partial thromboplastin time (aPTT) — a standard coagulation test that measures the time it takes for blood to clot — also was assessed before and after the transition to Hemlibra. Values of aPTT longer than normal are indicative of a clotting disorder, however the definition of a normal time range may vary by test and medical institution.
Other parameters assessed in the study included treatment duration before and after Hemlibra, reasons for switching to Hemlibra, the presence of other conditions, side effects, and treatment during surgery.
Results showed a significant reduction in median total ABR, which fell from 0.25 to 0, after switching to Hemlibra. A significant decrease in spontaneous, traumatic, and joint ABR was also observed. Also, no bleeding episodes or cases of inhibitor development were observed in either previously untreated or minimally treated children.
No serious side effects were revealed by safety analyses. A local injection site reaction occurred in two patients, but interrupting treatment was not necessary.
In patients who had undergone surgery, no bleeding occurred during and after the procedure.
“We show that minor surgery in patients receiving [Hemlibra] prophylaxis is safe and that no bleeding or thrombosis [blood clots] occurred, even if few doses of rFVIIa were administered additionally. Nevertheless, treatment strategies in case of major trauma or other major surgery should still be investigated in further studies,” the researchers wrote.
After three doses of 3 mg/kg, median Hemlibra levels were at 43.2 micrograms per milliliter (mcg)/ml, and at first follow-up with 1.5 mg/kg, median levels had increased to 51.9 mcg/ml.
According to the authors, “this went along with the already well documented effect of shortening the aPTT.” In fact, in this study, aPTT was reduced — from a median of 110 seconds to 27 seconds — with increasing levels of Hemlibra.
While the study showed that patients were treated safely and efficiently with Hemlibra, the researchers noted there is still much to explore.
“In the future, there might be patients in this cohort being treated with different dosing regimen (e.g. once every four weeks) and further studies with other dosing regimens may offer new insights,” they wrote.