Study: Roche's emicizumab cuts bleed rate by 87 percent in patients with haemophilia A

Roche announced Monday that the experimental drug emicizumab cut the bleed rate by 87 percent in adults and adolescents with haemophilia A with inhibitors compared to those who used bypassing agents (PBAs) in a Phase III study. Results from the HAVEN 1 trial, as well as those from the late-stage HAVEN 2 study in children younger than 12 years of age with haemophilia A with inhibitors, are scheduled to be presented next month at the International Society on Thrombosis and Haemostasis (ISTH) meeting.

The HAVEN 1 trial enrolled 109 patients 12 years of age or older with haemophilia A with inhibitors to factor VIII, who were previously treated with on-demand or prophylactic BPAs. Roche noted that patients previously treated with on-demand BPAs were randomised to receive once-weekly subcutaneous emicizumab prophylaxis or no prophylaxis. Meanwhile, patients previously treated with prophylactic BPAs received emicizumab prophylaxis, with additional subjects previously on BPA enrolled in a separate arm.

The study's primary endpoint is the number of treated bleeds over time with emicizumab prophylaxis compared with no prophylaxis. According to Roche, results showed that after a median observation time of 31 weeks, 62.9 percent of patients receiving emicizumab experienced zero treated bleeds compared to 5.6 percent of those receiving on-demand BPAs. The drugmaker added that the reduction in bleed rate with emicizumab was consistent across all secondary endpoints, including all bleeds, treated spontaneous bleeds, treated joint bleeds and treated target joint bleeds versus on-demand BPAs.

Analysts called the findings convincing, with Jefferies saying it underpins its $5 billion peak sales forecast for emicizumab. "If full presentation of the data at the ISTH reassure on safety, our mid-term EPS estimates and valuation could increase by 2 percent to 4 percent," Jefferies' analyst Jeffrey Holford noted.

However, analysts cautioned over a number of adverse events in the study, including thrombotic microangiopathy as a result of repeated high doses of bypassing agents to treat breakthrough bleeds. "From a safety perspective, treatment with this drug will require physicians to carefully manage the use of bypassing agents," said Vontobel's Stefan Schneider, which the analyst suggested "could limit uptake."

Roche said that in HAVEN 1, serious adverse events of thromboembolic events and thrombotic microangiopathy occurred in two patients and three patients, respectively, while receiving emicizumab prophylaxis. The company disclosed earlier this year, that one patient died in the trial after receiving emicizumab (for related analysis, see KOL Views: Leading haematologists sound off on the future of Roche's emicizumab in light of death in HAVEN 1 trial).

Roche on Monday also disclosed interim results from the HAVEN 2 study, which enrolled children younger than 12 years of age with haemophilia A with inhibitors who received emicizumab prophylaxis. The company said that the data are "consistent" with the positive results from the HAVEN 1 study.

Emicizumab, also known as ACE910, was created by Chugai Pharmaceutical and is being co-developed with Roche. The Swiss drugmaker plans to seek FDA approval for the therapy this year in patients with inhibitors, with follow-on submissions in 2018 including for patients without resistance. However, Deutsche Bank analysts said the latest data suggested it would be tough for emicizumab to make headway among those patients, however, since clotting factors appeared to be more effective for them. "Current therapy in the non-inhibitor setting provides a very high hurdle to new entrants and we believe emicizumab's less than perfect efficacy and observed thrombotic events will temper enthusiasm for the drug," Deutsche Bank's Tim Race remarked.