Hemlibra Lowered Number of Hemophilia A Bleeds Over Nearly 6 Years

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by Joana Carvalho |

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When given as a preventive treatment for nearly six years, Hemlibra (emicizumab) safely and effectively lowered the number of bleeding episodes in patients with severe hemophilia A, according to data from a Phase 1 clinical trial and its long-term extension study.

Importantly, reductions in the number of bleeds that required treatment with blood-clotting agents were seen in all patients, regardless of the presence of inhibitors or prior prophylactic (preventive) treatment.

Those findings were reported in the study, “Long‐term safety and efficacy of emicizumab for up to 5.8 years and patients’ perceptions of symptoms and daily life: A phase 1/2 study in patients with severe haemophilia A,” published in the journal Haemophilia.

Hemophilia A is caused by the lack of a functional blood-clotting protein, called factor VIII (FVIII). Conventional treatments for the disease consist of providing the missing FVIII to patients prophylactically to avoid bleeds — a form of treatment known as replacement therapy.

However, approximately a third of these patients end up developing inhibitors (neutralizing antibodies) to these treatments, rendering them useless.

Originally developed by Chugai Pharmaceutical and now marketed by Genentech, Hemlibra is an antibody-based therapy that has been approved in several countries worldwide as a routine prophylactic treatment for patients with hemophilia A with and without FVIII inhibitors.

The therapy is a bi-specific antibody that is able to bind to the activated form of factor IX (FIX) and factor X (FX), mimicking the normal function FVIII and promoting blood clotting.

Several clinical trials have demonstrated that, on a relatively short-term basis, Hemlibra was able to safely and effectively prevent bleeding episodes in children and adults with hemophilia A. However, data on its safety and effectiveness on a long-term basis were limited.

Here, investigators at Chugai and their collaborators in Japan reported the findings of a Phase 1 trial (JapicCTI-121934) and its Phase 1/2 extension study (JapicCTI-132195) that sought to assess the safety and efficacy of Hemlibra in 18 Japanese patients with severe hemophilia A, ages 12 to 58, with and without inhibitors.

During the Phase 1 study, participants were assigned to receive one of three different doses of Hemlibra (0.3, 1.0, or 3.0 mg/kg), which was given by under-the-skin injections, every week, for 12 weeks.

After completing this initial treatment period, participants had the option to enroll in the study’s long-term extension study and continue treatment with Hemlibra until the therapy became commercially available.

Initially, all patients continued receiving Hemlibra at the dose they had been assigned to in the main trial. However, those who did not achieve full control over their bleeds had the option to increase their dose to 1.0 or 3.0 mg/kg. Later, all patients started receiving the therapy at its approved maintenance dose of 1.5 mg/kg every week.

Previous data from the 12-week study showed that when given once weekly  Hemlibra was able to lower the annual bleeding rate (ABR) in all patients, regardless of inhibitors. In a follow-up study, data from 16 patients who had entered and been followed in the trial’s extension study for up to 2.8 years continued to show Hemlibra was safe and effective at preventing bleeds.

The researchers now reported data from all 18 patients who had been followed for up to 5.8 years in the studies.

Pooled data from the studies showed that in all dose groups, Hemlibra either lowered or maintained close to zero the ABRs for bleeds that required treatment with blood-clotting agents in all patients, regardless of inhibitors or prior prophylactic treatment. The largest reduction in ABRs for treated bleeds was seen in participants receiving the lowest dose of Hemlibra, where ABRs dropped from 32.46 before they started treatment to 1.25 while receiving the therapy. Median ABRs for treated bleeds among those receiving Hemlibra at a dose of 1.0 or 3.0 mg/kg, remained close to zero (0.83 with 1.0 and 0.22 with 3.0 mg/kg) during treatment. Importantly, of the eight patients in whom Hemlibra was lowered from 3.0 mg/kg to the approved maintenance dose of 1.5 mg/kg, only two saw their ABRs increase.Analyses of patient-reported outcomes gathered through a questionnaire also revealed all patients thought treatment with Hemlibra had lowered the severity of their bleeding episodes.Most also claimed their daily life and feelings, such as motivation to learn or work, had “improved” or “slightly improved” after starting treatment. With the exception of one patient, all others felt their anxiety symptoms also had become more manageable after beginning treatment with Hemlibra.

Safety analyses also showed that even though all patients experienced at least one side effect, most of them were mild in severity (89.4%). All three severe side effects, which included appendicitis and a femur fracture, were not related to Hemlibra. No new safety concerns were identified since the previous update of the trial’s long-term extension study.

“This study showed the remarkable efficacy and favorable safety of emicizumab [Hemlibra] prophylaxis for up to 5.8 years in patients with severe hemophilia A, and highlights the potential of emicizumab prophylaxis to improve both in the quantity and quality of patients’ bleeding symptoms, daily lives and feelings,” the researchers wrote.