Emicizumab Prevents Bleeds in Hemophilia Regardless of FVIII-Inhibitor Status

By Anne Harding

April 26, 2019

NEW YORK (Reuters Health) - Emicizumab given every four weeks provides adequate bleeding prophylaxis in hemophilia patients, regardless of coagulation factor VIII inhibitor status, a phase 3 trial shows.

"It's a landmark innovation for hemophilia in general, and based on efficacy research from these studies and what we're seeing in our clinics, this may be setting a new standard of care for what bleeding control can look like for patients," Dr. Steven W. Pipe of the University of Michigan in Ann Arbor, the study's first author, told Reuters Health by email.

Protein replacement therapy has been the standard treatment for patients with severe hemophilia for the past 50 years, Dr. Pipe noted. These patients require intravenous infusions of factor VIII (FVIII) every other day, and up to 30% develop antibodies to the clotting factor, severely limiting their treatment options. These patients must receive bypass therapy with recombinant activated FVII or activated FIX complex.

The U.S. Food and Drug Administration first approved emicizumab (Hemlibra, F. Hoffmann-La Roche) 1.5 mg/kg weekly for hemophilia patients with FVIII inhibitors in 2017; every-two-week and every-four-week regimens were approved irrespective of FVIII inhibitors in 2018.

In the HAVEN 4 trial, Dr. Pipe and colleagues report on 48 patients with hemophilia A aged 12 and older treated with emicizumab, including a pharmacokinetic run-in cohort of seven patients and an additional 41 enrolled in the study's expansion phase.

The run-in cohort received 6 mg/kg emicizumab subcutaneously every four weeks for 24 weeks. Patients who had a suboptimal response could choose to increase their dose to 3 mg/kg weekly for four weeks. The expansion cohort received 3 mg/kg every week for four weeks and then 6 mg/kg every four weeks for at least 24 weeks.

Twelve percent of patients in the expansion cohort had FVIII inhibitors at baseline; 17% of those without FVIII inhibitors had a history of such inhibitors.

The model-based annualized bleed rate was 2.4 for treated bleeds, and 4.5 for all bleeds. Just one-quarter of treated bleeds were spontaneous, while the rest were due to trauma.

Twenty-three patients (56.1%) had no treated bleeds, while 37 (90%) had no more than three. Thirty-five (85%) had no treated target joint bleeds.

Emicizumab is structurally completely different from FVIII, so it doesn't induce the formation of inhibitors, and is also effective in patients with inhibitors, Dr. Pipe noted. While the drug is expensive, its cost is in line with protein replacement therapy, and it is far less costly than treatment for patients with inhibitors, he said.

Patients taking emicizumab can also take FVIII when they need additional protection, Dr. Pipe added. "We can still use factor VIII as we normally would and there doesn't seem to be any adverse events associated with doing that," he said.

Worldwide, 80% of hemophilia patients have no adequate treatment, the researcher said. "Hopefully the cost can be worked out at a national health system level in order to bring it to as many patients as possible."

In an editorial accompanying the study, online April 16 in Lancet Haematology, Dr. Margaret V. Ragni of the University of Pittsburgh Medical Center writes: "If confirmed in longer-term follow-up of patients in clinical practice, a less frequent dosing strategy appears to be a reasonable treatment approach."

SOURCE: https://bit.ly/2IBOgm9 and https://bit.ly/2XFlqF2

Lancet Haematol 2019.