Interim Analysis of Phase III HAVEN 6 Study Demonstrates Favorable Safety and Efficacy of Roche’s Hemlibra in Patients with Moderate or Mild Hemophilia A Without Factor VIII Inhibitors

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On December 13, Roche announced the interim analysis results of the Phase 3 HAVEN 6 study. The data showed that Hemlibra (emizumab, emicizumab) demonstrated good safety and effective bleeding control in patients with moderate or mild hemophilia A without factor VIII inhibitors.

Currently, well-established treatment guidelines exist for severe hemophilia A, but there is limited information and guidance regarding moderate and mild hemophilia A, which may lead to delayed or missed diagnosis of bleeding events. Considering that this population may not use prophylactic treatment, they could experience a greater clinical burden, with less than 30% of moderate or mild hemophilia A patients living without bleeding episodes.

HAVEN 6 is a Phase 3 study conducted in patients with moderate or mild Hemophilia A without Factor VIII inhibitors, evaluating the safety, efficacy, pharmacokinetics, and pharmacodynamics of Hemlibra. The interim analysis now published includes data from 71 patients (69 males and 2 females), of whom 20 were patients with mild Hemophilia A without Factor VIII inhibitors and 51 were patients with moderate Hemophilia A without Factor VIII inhibitors. At baseline, 37 patients were receiving prophylactic treatment with Factor VIII.

The interim analysis was conducted after 50 patients with moderate hemophilia A completed at least 24 weeks of treatment in the study or withdrew from the study. The data cutoff date was April 16, 2021. These data indicate that Hemlibra demonstrated a favorable safety profile and effective bleed control in the HAVEN 6 study, with 80.3% of patients experiencing no treated bleeds and 90.1% experiencing no treated joint bleeds. The annualized bleeding rate (ABR) remained low, consistent with previously reported results from the HAVEN 1-4 studies. Additionally, among the 50 patients aged 12 years or older who responded to the EmiPref questionnaire, 48 (96.0%) preferred Hemlibra over their previous treatment.

In the HAVEN 6 study, the most common adverse events (AEs) occurring in 10% or more patients were headache (14.1%) and local injection site reactions (ISR) (12.7%). Eleven patients (15.5%) reported Hemlibra-related AEs, with ISR being the most common (12.7%). As of the data cutoff date, no deaths, thrombotic microangiopathy (TMA), or serious thrombotic events (TE) occurred in the study, reinforcing Hemlibra's favorable safety profile.

A separate analysis of TE and TMA events in the Hemlibra-treated population, including real-world data, was also presented as a poster at the ASH Annual Meeting. These results indicate that with increased exposure, the assessment of reported non-aPCC (activated prothrombin complex concentrate) events is consistent with prior analyses, and Hemlibra’s benefit/risk profile remains unchanged. These data further confirm Hemlibra’s favorable safety profile, consistent with previous findings from the HAVEN and STASEY studies.

Hemlibra is a humanized bispecific monoclonal antibody. Its bispecific structure functions like two arms, bringing together the proteins needed to activate the natural coagulation cascade—activated factor IX and factor X—thereby restoring the clotting process in patients with hemophilia A and making it possible for hemophilia A patients to achieve a goal of zero bleeding.

In clinical studies, Hemlibra has been shown to significantly reduce bleeding episodes and improve physical function. For patients with factor VIII inhibitors (anti-FVIII antibodies), Hemlibra can still work effectively. Moreover, since Hemlibra has no structural or sequence homology with factor VIII, it does not induce or enhance the production of direct factor VIII inhibitors.

To date, Hemlibra has been approved in more than 100 countries worldwide for the treatment of patients with hemophilia A who have factor VIII inhibitors, and in over 90 countries for patients with hemophilia A who do not have factor VIII inhibitors, to prevent or reduce the frequency of bleeding episodes. Hemlibra has been studied in the largest clinical trial program, which includes eight Phase III studies enrolling patients with hemophilia A both with and without factor VIII inhibitors.

In China, Hemlibra (Soliris®, emicizumab) was approved in December 2018 for routine prophylactic treatment in adult and pediatric patients with hemophilia A (congenital factor VIII deficiency) who have factor VIII inhibitors, to prevent or reduce the frequency of bleeding. In May 2021, Hemlibra received approval in China for a new indication: routine prophylactic treatment in adult and pediatric patients with severe hemophilia A (congenital factor VIII deficiency, FVIII<1%) without factor VIII inhibitors.

Reference Source: Interim data from phase III HAVEN 6 study demonstrate favourable safety and efficacy profile of Roche’s Hemlibra in people with moderate or mild haemophilia A