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Photo by Bill Branson

GLASGOW—Emicizumab prophylaxis provides “clinically meaningful” control of bleeding whether or not patients have factor VIII inhibitors, according to researchers.

In the phase 3 HAVEN 4 study, researchers evaluated emicizumab prophylaxis, given every 4 weeks, in hemophilia A patients with or without factor VIII inhibitors.

At a median follow-up of about 26 weeks, patients had a median annualized bleeding rate (ABR) of 0.0 for treated bleeds and 2.1 for all bleeds.

About 30% of patients had 0 bleeds, and about 56% had 0 treated bleeds.

There were no serious adverse events (AEs) related to emicizumab. The most common AE was injection-site reaction.

Steve Pipe, MD, of Mott Children’s Hospital in Ann Arbor, Michigan, presented these results at the World Federation of Hemophilia (WFH) 2018 World Congress during the late-breaking abstract session on Monday.

The trial was sponsored by Hoffmann-La Roche.

HAVEN 4 included 48 patients, age 12 and older, who had hemophilia A with or without factor VIII inhibitors. Patients were previously treated with factor VIII or bypassing agents, on-demand or as prophylaxis.

The study was conducted in 2 parts: a pharmacokinetic (PK) run-in and an expansion cohort.

All patients in the PK run-in (n=7) were previously treated on-demand and received subcutaneous emicizumab at 6 mg/kg to fully characterize the PK profile after a single dose during 4 weeks. This was followed by 6 mg/kg every 4 weeks for at least 24 weeks.

Patients in the expansion cohort (n=41) received subcutaneous emicizumab prophylaxis at 3 mg/kg/wk for 4 weeks, followed by 6 mg/kg every 4 weeks for at least 24 weeks.

Episodic treatment of breakthrough bleeds with factor VIII therapy or bypassing agents, depending on a patient’s factor VIII inhibitor status, was allowed per study protocol.


The efficacy analysis included the 41 patients in the expansion cohort, 5 of whom had inhibitors at baseline.

The median efficacy period was 25.6 weeks. The median ABR was 2.1 for all bleeds and 0.0 for treated bleeds.

The percentage of patients with 0 bleeds was 29.3% for all bleeds, 56.1% for treated bleeds, 82.9% for treated spontaneous bleeds, 70.7% for treated joint bleeds, and 85.4% for treated target joint bleeds.

Most treated bleeds (74.5%, 38/51) were traumatic.

There were 148 AEs, and 73.2% of patients had at least 1 AE.

Injection-site reaction was the most common AE related to emicizumab, occurring in 22.0% of patients (n=9).

There were 2 serious AEs (grade ≥3)—hypertension and rhabdomyolysis. Both were considered unrelated to emicizumab.

There were no AEs leading to emicizumab discontinuation or withdrawal. There were no thrombotic events, cases of thrombotic microangiopathy, hypersensitivity reactions, or fatalities.

None of the patients developed de novo factor VIII inhibitors, and there were no anti-drug antibodies detected.

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