Hemlibra controls hemophilia A bleeds over nearly 5 years: Analysis
Data from 191 hemophilia A patients from HAVEN 3, HAVEN 4 trials studied
Hemlibra (emicizumab-KXWH) safely controlled bleeds among hemophilia A patients without inhibitors over nearly five years of preventive treatment, according to long-term data pooled from two Phase 3 clinical trials.
“Five years of follow-up data showed a favorable benefit-risk profile of [Hemlibra] prophylaxis,” the researchers wrote in “Long-term outcomes with emicizumab in hemophilia A without inhibitors: results from the HAVEN 3 and 4 studies,” which was published in Research and Practice in Thrombosis and Haemostasis.
Hemlibra is an antibody-based therapy for preventing or reducing bleeds in hemophilia A, a blood-clotting disorder marked by a deficiency in factor VIII (FVIII), a clotting protein. Originally developed by Chugai Pharmaceutical, which is now part of the Roche group, it binds to clotting factors IX and X, mimicking the action of FVIII to prevent or lower the occurrence of bleeding episodes.
Hemlibra was first approved in the U.S. in 2017 as a preventive treatment for children and adults with hemophilia A with inhibitors, that is, antibodies that neutralize FVIII. Its approval was extended to hemophilia A patients without FVIII inhibitors in 2018.
Safety, efficacy of Hemlibra in hemophilia A
Here, the researchers presented combined long-term safety and efficacy data from HAVEN 3 (NCT02847637) and HAVEN 4 (NCT03020160), two open-label Phase 3 studies that supported Hemlibra’s approval in people without inhibitors to have more data on [the] long-term use of emicizumab by that patient population.
Across both trials, 191 patients received injections of Hemlibra under the skin, or subcutaneously, with an overall median exposure of 248.1 weeks (nearly five years). In HAVEN 3, they were treated with maintenance doses of 1.5 mg/kg every week or 3 mg/kg every two weeks. In HAVEN 4, 6 mg/kg doses were given every four weeks.
The mean annualized bleeding rate (ABR) for treated bleeds was 2.0 from weeks one to 24 (almost six months). This fell to 0.8 by weeks 217 to 240. For all bleeds, the ABR decreased from 3.4 to 1.0 over the same period. When assessed over 24-week periods, the proportion of participants with no treated bleeds increased from 62.2% to 78.8% in the same period.
Nearly half (48.8%) of the participants had no spontaneous or traumatic joint bleeds over the efficacy period. Of the 306 target joints present before treatment, 291 (95.1%) were free of spontaneous or traumatic bleeds in the first year after Hemlibra was started. During the last year, 297 (97.1%) target joints had no spontaneous or traumatic bleeds. Here, target joints are those where there were at least three joint bleeds over 24 weeks.
Using FVIII replacement products to treat bleeds generally decreased over time, with the mean annualized infusion rate dropping from 3.6 at weeks 1-24 to 1.9 at weeks 217-240. Likewise, the annualized consumption of FVIII decreased over the same period, from a mean of 110.3 to 53.0 U/kg.
A total of 185 treatment-related side effects were reported by 71 (37.2%) participants across the two studies. The most common treatment-related side effects included injection-site reactions (28.8%), headache (2.6%), rash (1.6%), itching (1.0%), and nausea (1.0%). Although 44 (23.0%) participants reported a serious side effect event, none were deemed to be related to Hemlibra.
No participants reported developing FVIII inhibitors in either HAVEN 3 or HAVEN 4 during follow-up.
A high number of participants continued using Hemlibra after completing the trials, either via a post-trial access program or by switching to the commercial version, researchers said.
Over nearly five years of follow-up, “these data build on previous findings of a favorable long-term benefit-risk profile for [Hemlibra] prophylaxis in people with [hemophilia A] without inhibitors, with consistent bleed prevention and no new or unexpected safety signals,” they wrote.
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