Hemlibra Data Show Sustained Bleed Reductions in Hemophilia A Patients with Inhibitors

José Lopes, PhD avatar

by José Lopes, PhD |

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FVIII inhibitors

Clinical trials of Hemlibra (emicizumab-kxwh) continue to show significant reductions in bleeding episodes in patients with hemophilia A with inhibitors, Genentech recently announced.

Data from Hemlibra’s clinical development program were presented at the 59th American Society of Hematology (ASH) Annual Meeting.

The results show that in hemophilia A patients with inhibitors to clotting factor VIII, preventive treatment, or prophylaxis, with once-weekly subcutaneous injections of Hemlibra is significantly more effective than prior treatment with bypassing agents (BPAs), both as prophylaxis or on-demand.

The data come from additional months of treatment and the inclusion of more patients in the pivotal HAVEN 1 (NCT02622321) and HAVEN 2 (NCT02795767) studies.

The Phase 3 HAVEN 1 trial compares the effectiveness, safety, and pharmacokinetics (how the body interacts with a therapy) of once-weekly subcutaneous injections of Hemlibra prophylaxis in adult and adolescent hemophilia A patients with inhibitors to factor VIII to patients who did not receive prophylaxis.

A total of 113 patients 12 and older were included. Those previously treated with BPAs on-demand were randomly assigned either to Hemlibra or no prophylaxis. Patients treated with BPAs as prophylaxis received Hemlibra prophylaxis.

An additional 10 months of data revealed an 88% reduction in treated bleeds with Hemlibra in adults and adolescents compared to prior BPA prophylaxis. In addition, a 95% reduction in treated bleeds compared to prior on-demand BPA treatment was observed. Hemlibra prophylaxis enabled more patients to experience zero bleeds after more than one year of treatment.

The HAVEN 2 trial is evaluating once-weekly subcutaneous administration of Hemlibra in children younger than 12. The updated results in 60 children showed that about 95% of children receiving Hemlibra had zero treated bleeds. Furthermore, a 99% decrease in treated bleeds was seen with Hemlibra, compared with both treatment regimens with BPAs. Significant improvements in health-related quality of life and caregiver burden also were seen.

No adverse events resulted in discontinuation of the treatment in both the HAVEN 1 and HAVEN 2 studies. Reported adverse events in the follow-up data are consistent with those observed previously. No new cases of thrombotic microangiopathy (a small-blood-vessel disease) or thrombotic events were detected in HAVEN 1, and no episodes occurred in HAVEN 2.

“These data demonstrate the continued reduction in bleeds over time with Hemlibra prophylaxis and reinforce the potential of this medicine, recently approved by the FDA for hemophilia A with inhibitors, to redefine the standard of care,” Sandra Horning, chief medical officer and head of Global Product Development at Genentech, said in a press release.

The company is advancing its study of Hemlibra in diverse types of patients and designing less frequent dosing regimens, Horning said.

The development program also includes the ongoing Phase 3 HAVEN 3 (NCT02847637) and HAVEN 4 (NCT03020160) studies.

In HAVEN 3, researchers saw a significant drop in treated bleeds in patients 12 and older with hemophilia A without inhibitors. These patients received Hemlibra prophylaxis every week or every other week.

In HAVEN 4, six out of seven patients 12 and older, with or without inhibitors, who received Hemlibra had no bleeds after approximately eight weeks of observation. The therapy was dosed every four weeks for at least 24 weeks. Genentech recently announced the results of an interim analysis of HAVEN 4.

Hemlibra is a bispecific factor IXa- and factor X-directed antibody. These clotting factors are required to activate the body’s coagulation cascade.

The therapy is being co-developed by Japan’s Chugai Pharmaceuticals, Switzerland’s Roche, and Roche’s subsidiary, Genentech.

Based on earlier results from HAVEN 1 and 2, the treatment is currently approved by the FDA for routine prophylaxis to prevent or minimize the frequency of bleeding episodes in adults and children with hemophilia A with factor VIII inhibitors.

The European Medicines Agency (EMA) recently recommended the approval of Hemlibra for routine prophylaxis in a similar patient group.