The safety profile of emicizumab prophylaxis was confirmed in a large, international population of patients with hemophilia A and factor VIII (FVIII) inhibitors, according to results from the STASEY study published in Research and Practice in Thrombosis and Haemostasis.
According to researchers, the previous HAVEN clinical trials were pivotal in establishing emicizumab as safe and effective in people with hemophilia A with and without FVIII inhibitors. Victor Jiménez-Yuste, MD, PhD, of Autónoma University in Madrid, and colleagues sought to confirm the safety and efficacy of emicizumab for routine bleeding prophylaxis in patients with hemophilia A with FVIII inhibitors following findings of the HAVEN trials.
The STASEY study, which ran from September 2017 to November 2020, included 195 male patients from across the globe, including countries not involved in the HAVEN program. Patients were at least 12 (median age = 28) and had congenital hemophilia A and FVIII inhibitors.
Participants received 3 mg/kg emicizumab subcutaneously once weekly (QW) for four weeks, followed by 1.5 mg/kg emicizumab QW for the remainder of the two-year treatment period. Researchers recorded the number and severity of adverse events (AEs), including thrombotic events (TEs) and thrombotic microangiopathies (TMAs). Researchers also measured the efficacy of emicizumab through participant-recorded bleeds using an electronic patient-reported outcome device. The study’s clinical endpoints were aligned with the HAVEN trials to allow for comparisons between the studies.
Of 195 patients, two discontinued the study before receiving therapy, nine discontinued for various reasons unrelated to the therapy, and 186 (95.4%) completed the study. Zero participants reported a TMA, and 161 participants (82.6%) had zero treated bleeds during the study.
Overall, 163 evaluable participants experienced a total of 800 AEs during the study, the most common of which were arthralgia (17.1%), nasopharyngitis (15.5%), and headache (15%). AEs that were considered related to emicizumab occurred in 18.1% of patients; all but two AEs were grade 1, and the most common was injection site reaction (9.8%). Thirty-one participants (16.1%) reported 50 serious adverse events (SAEs), two of which were attributed to emicizumab.
In line with the HAVEN clinical trials, two participants (1.0%) experienced TEs, neither of which were considered to be related to emicizumab prophylaxis. Still, “an association with emicizumab cannot be definitively excluded,” researchers said.
The mean annual bleed rate (ABR) for treated bleeds while receiving emicizumab was 0.6, lower than the ABR of 1.4 observed in HAVEN 1. Researchers said the difference “could reflect contrasting approaches to treating bleeds in this broader range of countries [than HAVEN], perhaps due to variability or lack of resources.”
Of 136 treated bleeds recorded, 13 were treated with activated prothrombin complex concentrate and 112 were treated with recombinant factor VIIa.
Two participants had dose up-titration to 3 mg/kg a week with no indication of anti-drug antibodies (ADAs) throughout the study. While 10 evaluable participants (5.2%) tested positive for ADAs, all participants tested negative for ADAs at their last visit.
“The presence of ADAs did not have an impact on PK [pharmacokinetics], PD [pharmacodynamics], or bleeding and did not alter the safety profile of emicizumab,” researchers said.
Finally, emicizumab prophylaxis demonstrated an improvement in both quality of life and health status, as measured by participant surveys.
Researchers cited the single-arm study design and the use of only one approved dosing regimen as limitations. Accordingly, “caution should be exercised when extrapolating these results to the other two approved dosing regimens,” researchers said.
Altogether, researchers said, “the STASEY study confirmed the safety profile of emicizumab 1.5 mg/kg QW in adolescent and adult people with [hemophilia A] with FVIII inhibitors over a two-year treatment period. No new or unexpected safety signals were observed.”
Any conflicts of interest declared by the authors can be found in the original article.
Khylia Marshall is a freelance journalist based in Tucson, Arizona.
Reference
Jiménez-Yuste V, Peyvandi F, Klamroth R, et al. Safety and efficacy of long-term emicizumab prophylaxis in hemophilia A with factor VIII inhibitors: A phase 3b, multicenter, single-arm study (STASEY). Res Pract Thromb Haemost. 2022;6:e12837.