General Information

Hemlibra (emicizumab-kxwh) is a bispecific factor IXa- and factor X-directed antibody.

Hemlibra is specifically indicated for routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients ages newborn and older with hemophilia A (congenital factor VIII deficiency) with or without factor VIII inhibitors.

Hemlibra is supplied as a solution for subcutaneous injection. The recommended loading dose is 3 mg/kg by subcutaneous injection once weekly for the first 4 weeks, followed by a maintenance dose of:

• 1.5 mg/kg once every week, or

• 3 mg/kg once every two weeks, or

• 6 mg/kg once every four weeks

Clinical Results

FDA Approval

The initial FDA approval of Hemlibra was based on data from two clinical trials. The first was a trial that included 109 males aged 12 and older with hemophilia A with FVIII inhibitors. The randomized portion of the trial compared Hemlibra to no prophylactic treatment in 53 patients who were previously treated with on-demand therapy with a bypassing agent before enrolling in the trial. Patients taking Hemlibra experienced approximately 2.9 treated bleeding episodes per year compared to approximately 23.3 treated bleeding episodes per year for patients who did not receive prophylactic treatment. This represents an 87 percent reduction in the rate of treated bleeds. The trial also included patient-reported Quality of Life metrics on physical health. Patients treated with Hemlibra reported an improvement in hemophilia-related symptoms (painful swellings and joint pain) and physical functioning (pain with movement and difficulty walking) compared to patients who did not receive prophylactic treatment. The second trial was a single arm trial of 23 males under the age of 12 with hemophilia A with FVIII inhibitors. During the trial, 87 percent of the patients taking Hemlibra did not experience a bleeding episode that required treatment.

The expanded FDA approval- to include patients of all ages with or without factor VIII inhibitors- was based on two clinical trials: HAVEN 3 and HAVEN 4.

In HAVEN 3, a randomized, multicenter, open-label trial, 89 patients with severe hemophilia A without FVIII inhibitors who previously received episodic (on demand) treatment with FVIII were randomized (2:2:1) to receive Hemlibra prophylaxis 1.5 mg/kg once every week (Arm A), 3 mg/kg once every two weeks (Arm B), or no prophylaxis (Arm C). Patients were stratified by 24-week bleed rate prior to trial entry (< 9 or ≥ 9 bleeds). Patients received Hemlibra prophylaxis for a minimum of 24 weeks. The primary efficacy endpoint was the annualized bleed rate (ABR) for treated bleeds. Hemlibra prophylaxis in Arm A resulted in a 96% reduction in ABR compared with Arm C. Hemlibra prophylaxis in Arm B also led to a 97% reduction in ABR compared with Arm C. HAVEN 3 also met all bleed-related secondary endpoints (all bleeds, treated spontaneous bleeds, treated joint bleeds and treated target joint bleeds).

HAVEN 4 was a single-arm, multicenter, open-label trial in 48 adult and adolescent males with hemophilia A with or without FVIII inhibitors who previously received either episodic (on demand) or prophylactic treatment with FVIII or bypassing agents. Patients in the expansion cohort (n=41) received Hemlibra prophylaxis 6 mg/kg once every four weeks for at least 24 weeks. The ABR for treated bleeds was 2.4 and the median ABR was 0.0.

Side Effects

Adverse effects associated with the use of Hemlibra may include, but are not limited to, the following:

injection site reactions

headache

arthralgia

The Hemlibra drug label comes with the following Boxed Warning: Cases of thrombotic microangiopathy and thrombotic events were reported when on average a cumulative amount of >100 U/kg/24 hours of activated prothrombin complex concentrate (aPCC) was administered for 24 hours or more to patients receiving Hemlibra prophylaxis. Monitor for the development of thrombotic microangiopathy and thrombotic events if aPCC is administered. Discontinue aPCC and suspend dosing of Hemlibra if symptoms occur.