Final Analysis of the STASEY Study: How Did Emicizumab Fare in the Prophylaxis of Hemophilia A Patients with FVIII Inhibitors?

Introduction

Emicizumab is a bispecific antibody that creates a link between activated factor IX (IXa) and factor X, proteins involved in the natural coagulation cascade. It replaces the function of the missing FVIII, which acts as a cofactor in this reaction, thereby restoring hemostasis. It is administered worldwide in clinical practice for the prophylaxis of bleeding episodes in hemophilia A patients, both with and without FVIII inhibitors, in both adults and children. It is administered via subcutaneous injection once weekly, every 2 weeks, or every 4 weeks.

The STASEY study now provides further insights regarding its use in both adults and older children.

Study Design and Objectives

The study population consisted of patients diagnosed with hemophilia A and an FVIII inhibitor, aged at least 12 years. They received subcutaneous emicizumab first at a loading dose of 3 mg/kg once weekly for 4 weeks, followed by a maintenance dose of 1.5 mg/kg once weekly. Emicizumab prophylaxis lasted up to 2 years. 

The primary objective was to evaluate the incidence of potential adverse events associated with emicizumab administration, including thromboembolic (TE) events, thrombotic microangiopathy (TMA), and hypersensitivity reactions. Secondary objectives included assessing the efficacy of the drug, expressed as annual bleeding rate (ABR), and the development of anti-drug antibodies (ADA).

Results

As of the last visit of the final participant (November 19, 2020), 193 patients had received ≥ 1 dose of emicizumab, with a median age of 28 years (12–80). The median duration of treatment was 103.1 weeks (1.1–108.3).

Emicizumab was well tolerated. The most common adverse events were arthralgia (17.1%, n = 33), nasopharyngitis (15.5%), and headache (15.0%, n = 29). No new TE events were observed since the two interim analyses. Adverse events related to emicizumab use were reported in 18.1% (35) of participants, most commonly injection site reactions (9.8%, n = 19). There was one death, which was considered unrelated to the study drug (the patient died from abdominal compartment syndrome). Five patients received activated prothrombin complex concentrate (aPCC) for prophylaxis with emicizumab, with no TMA or TE events associated with this treatment. ADA were developed by 5.2% (10) of individuals, with in vitro neutralization in 2.6% (5) of cases.

The median ABR for treated bleeds was 0.5, and zero treated bleeds were observed in 82.6% of study participants.

Conclusion

The safety profile of emicizumab, as demonstrated in the HAVEN clinical trials, was confirmed in a large and diverse population of hemophilia A patients with FVIII inhibitors, without revealing any new safety signals. The majority of participants in the STASEY study experienced no bleeding episodes requiring treatment.

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Source: Jiménez-Yuste V., Peyvandi F., Klamrot R. et al. Final analysis of the STASEY trial: a single-arm, multicenter, open-label, phase III clinical trial evaluating the safety and tolerability of emicizumab prophylaxis in persons with hemophilia A (PwHA) with factor (F)VIII inhibitors. ISTH Congress 2021. Res Pract Thromb Haemost 2021; 5 (Suppl. 1): PB0521. Available at: https://abstracts.isth.org/abstract/final-analysis-of-the-stasey-trial-a-single-arm-multicenter-open-label-phase-iii-clinical-trial-evaluating-the-safety-and-tolerability-of-emicizumab-prophylaxis-in-persons-with-hemophilia-a-pwha