Roche has announced positive data from the primary analysis of the phase III HAVEN 1 study in adults and adolescents and interim analysis of the phase III HAVEN 2 study in children evaluating once-weekly subcutaneous emicizumab prophylaxis (preventative) for the treatment of haemophilia A with inhibitors to factor VIII. Data from both studies will be presented on 10 July at the 26th International Society on Thrombosis and Haemostasis (ISTH) Meeting in Berlin, Germany.

The phase III HAVEN 1 study compared emicizumab prophylaxis with on-demand (no prophylaxis; episodic use only) and prophylactic use of bypassing agents (BPAs) in adults and adolescents with haemophilia A with inhibitors. The primary endpoint was treated bleeds, and results showed a statistically significant and clinically meaningful reduction in bleed rate of 87% (risk rate [RR]=0.13, p<0.0001) with emicizumab prophylaxis compared with on-demand treatment with BPAs.

After a median observation time of 31 weeks, 62.9% of patients receiving emicizumab experienced zero treated bleeds compared to 5.6% of those receiving on-demand BPAs. Reduction in bleed rate with emicizumab was consistent across all secondary endpoints, including all bleeds (80%, RR=0.20, p<0.0001), treated spontaneous bleeds (92%, RR=0.08, p=0.0001), treated joint bleeds (89%, RR=0.11, p=0.0050) and treated target joint bleeds (95%, RR=0.05, p=0.0002) compared with on-demand BPAs. Results also showed a statistically significant and clinically meaningful improvement in health-related quality of life (HRQoL) measured at 25 weeks, including Haem-A-Qol physical health domain and total score and EQ-5D-5L visual analogue scale and total utility score.

In an additional study arm (Arm C, n=49), patients who had previously received prophylaxis with BPAs received emicizumab prophylaxis. A subset of patients in this arm (n=24) had previously participated in a non-interventional study (NIS), allowing for a first of its kind intra-patient analysis. This analysis showed a 79% (RR=0.21, p=0.0003) reduction in treated bleeds in people receiving emicizumab compared to their prior prophylaxis with BPAs.

Adverse events (AEs) occurring in 5% or more of patients treated with emicizumab, were injection site reactions, headache, fatigue, upper respiratory tract infection and arthralgia. As previously reported, serious adverse events of thromboembolic events (TE) and thrombotic microangiopathy (TMA) occurred in two patients and three patients*, respectively, while receiving emicizumab prophylaxis. The TE and TMA events were associated with repeated high doses of a BPA, activated prothrombin complex concentrate, when used to treat breakthrough bleeds.

Interim results from the single arm HAVEN 2 study in children younger than 12 years of age with haemophilia A with inhibitors who received emicizumab prophylaxis are consistent with the positive results from the HAVEN 1 study. After a median observation time of 12 weeks, the study showed that only one of 19 children receiving emicizumab reported a treated bleed. There were no reported joint or muscle bleeds. An intra-patient comparison (n=8) in patients who were previously enrolled in the NIS, showed that all patients experienced a 100% reduction in treated bleeds following treatment with emicizumab (previous ABR ranged from 0 to 34.24); this included seven children who had received prior BPA prophylaxis, and one who had received prior on-demand BPA. The data also indicate that the same dose of emicizumab is appropriate for children as for adults and adolescents, based on the levels of emicizumab in the blood (pharmacokinetics) of the children compared with the level of emicizumab in the blood of adults and adolescents. The most common AEs with emicizumab in the HAVEN 2 study were mild injection site reactions and common cold symptoms (nasopharyngitis).