ATLANTA – The bispecific humanized monoclonal antibody emicizumab safely prevents or substantially reduces bleeds in children with hemophilia A with inhibitors that render standard factor VIII replacement therapies ineffective, according to an updated interim analysis of data from the open-label phase 3 .
Guy Young, MD, said during a press briefing at the annual meeting of the American Society of Hematology.
Of 57 patients under age 12 years receiving weekly subcutaneous emicizumab (Hemlibra) for bleeding prophylaxis at the data cutoff, 54 (94.7%) had zero treated bleeds, said of the University of Southern California, Los Angeles.
“That’s, honestly, truly remarkable. I mean, most of the time, these patients are bleeding at least on a monthly basis, sometimes more often than that,” he said.
Further, of 23 patients who were treated for at least 12 weeks and had a median efficacy period of 38.1 weeks, 87% had no bleeding events whatsoever (annual bleed rate of 0.2 events vs. a usual annual bleed rate of 1.3 events in patients without inhibitors). The annual treated joint bleed and treated target joint bleed rates each were 0.1, he said.
Overall, only three treated bleeds occurred in the 57 patients, and only one was a spontaneous bleed; one occurred in a joint, one occurred in a muscle, and one occurred in the hip and was classified as “other,” he noted.
The findings expand upon those from a previously reported interim analysis of data on 20 children from the study, which also showed that once-weekly subcutaneous emicizumab prophylaxis prevented or reduced bleeds, and provided clinically meaningful reductions in the annualized bleed rate when compared with prior bypassing agent treatment, Dr Young said.
In that prior analysis of participants aged 2-12 years (or up to 17 years with weight below 40 kg), which was presented in July at theof the International Society on Thrombosis and Haemostasis, the data cutoff was Oct. 28, 2016. The current analysis had a May 8, 2017 cutoff, and therefore included about 6 additional months of data.
The treatment, which is given at a dose of 3 mg/kg per week for 4 weeks and then 1.5 mg/kg per week thereafter, was well tolerated. Ten nonserious, treatment-related adverse events occurred, and mainly involved injection site reactions. Serious adverse events occurred in six patients but were mainly related to the disease or to the use of catheters, or were otherwise unrelated to emicizumab. There were no thromboembolic or thrombotic microangiopathy events reported. Mean steady state trough concentrations (approximately 50 mcg/mL) were consistent with the pharmacokinetic profile seen in prior studies in the adolescent/adult population.
Health-related quality of life improvements were considerable, and in many cases, dramatic, Dr. Young said, noting in an interview that, for some patients, the effects were life changing both for the patients and their families. He described one young patient who had experienced scores of debilitating ankle bleeds, but had had no bleeds since he began receiving treatment as part of this study.
Emicizumab, which recently received Food and Drug Administrationfor use in patients of all ages with hemophilia A with inhibitors, bridges factor IXa and factor X to “bring them into proper alignment, which is really what the function of factor VIII is,” he said.
“So, it’s essentially replacing, or mimicking, the function of factor VIII, but without being factor VIII,” he said, explaining that it can be used to treat patients with inhibitors, because the antibodies they develop are specifically to factor VIII.
“This is not factor VIII, it’s just doing the job of factor VIII,” he added.
Studies of emicizumab for hemophilia A without inhibitors are ongoing (), and could result in expanded indications, he noted.
The primary efficacy results of HAVEN 2 will be reported 52 weeks after the last patient is enrolled. These interim findings, however, demonstrate the potential for weekly subcutaneous injections of emicizumab to safely and conveniently reduce overall disease burden, as well as overall treatment burden in patients with hemophilia A with inhibitors, as these patients previously had to undergo intravenous treatment multiple times per week – and sometimes multiple times per day, he said.
The HAVEN 2 study is sponsored by Hoffman-La Roche. Dr. Young has received honoraria and/or consulting fees from Alnylam, Bayer, Bioverativ, CSL Behring, Genentech/Roche, Kedrion, Novo Nordisk, and Shire.
SOURCE: Young G et al. ASH 2017 .