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

Introduction

Emicizumab is a bispecific antibody creating a link between activated factor IX (IXa) and factor X, which are proteins participating 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 in clinical practice worldwide for the prophylaxis of bleeding episodes in hemophiliacs of type A both with and without the FVIII inhibitor, in both adults and children. It is administered via subcutaneous injection once a week, every 2 weeks, or every 4 weeks.

The STASEY study has now provided further insights into its use in both adults and older children.

Course and Objectives of the Study

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

The primary objective was to evaluate the occurrence of any adverse events associated with the administration of emicizumab, including thromboembolic (TE) events, the occurrence of thrombotic microangiopathy (TMA), and hypersensitivity reactions. The secondary objective was to assess the efficacy of the drug expressed as the annual bleeding rate (ABR) and the formation of anti-drug antibodies (ADA).

Results

By the date of the last visit of the last participant (November 19, 2020), 193 patients had received ≥ 1 dose of emicizumab, with a median age of 28 years (12–80). The median treatment duration 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%; n = 30), and headache (15.0%; n = 29). No new TE events occurred since the two interim analyses. Adverse events associated with emicizumab were reported in 18.1% (35) participants, most commonly injection-related reactions (9.8%; n = 19). There was one death, which was not related to the study drug (the patient died from abdominal compartment syndrome). Five patients received emicizumab prophylaxis along with activated prothrombin complex concentrate (aPCC), without any TMA or TE events associated with the drug's administration. ADA was detected in 5.2% (10) individuals, and in 2.6% (5) individuals it was neutralized in vitro.

The median ABR for treated bleeds was 0.5. A zero occurrence of treated bleeds was recorded in 82.6% of study participants.

Conclusion

The safety profile of emicizumab, as demonstrated by the clinical studies of the HAVEN program, was confirmed in a large and diverse population of hemophilia A patients with an FVIII inhibitor, without identifying any new safety signals. The majority of STASEY study participants experienced no bleeds 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