STASEY confirms safety, efficacy of emicizumab for PwHA with FVIII inhibitors
16 Aug 2021
The STASEY trial, a large, phase IIIb study evaluating a diverse population of persons with haemophilia A (PwHA) with Factor(F)VIII inhibitors, confirms the safety and efficacy profile of the bispecific monoclonal antibody emicizumab that has been demonstrated in the HAVEN trials.
The risk of bleeding (including life-threatening bleeds) is greater among PwHA with inhibitors than those who do not have inhibitors. [www1.wfh.org/publication/files/pdf-1122.pdf, accessed August 12, 2021] Emicizumab may restore haemostasis by bridging activated FIX and FX, replacing the function of defective or missing activated FVIII in these patients.
A total of 193 participants (median age 28 years) received SC emicizumab 3 mg/kg QW for 4 weeks followed by 1.5 mg/kg QW for up to 2 years. The primary goal was to assess the incidence of adverse events (AEs), including thromboembolic events and thrombotic microangiopathies. Secondary objectives were to ascertain its efficacy (annualized bleed rates [ABRs]) and antidrug antibody (ADA) development.
Second interim analysis: AEs
At a median treatment duration of 50.9 weeks, only one AE led to treatment withdrawal, while three led to dose modification/interruption. Two thromboembolic events were reported: hypertrophic clot following tooth extraction and ST-elevation myocardial infarction (STEMI). [ISTH 2021, abstract PB0958]
“[The STEMI patient] had several risk factors, including a history of smoking, hypertension, and family history of coronary heart disease. He did not receive bypassing agents and continued emicizumab without dose adjustment … [The] treating physician assessed the event as unrelated to emicizumab,” said the researchers. “The [clot] is a known complication of tooth extractions.”
Ten developed ADAs, but none had neutralizing potential. “[These patients] continued on emicizumab 1.5 mg/kg/week with no increased bleeding. ABRs remained low [with] no new safety signals identified,” noted the researchers. “[Our findings] confirm the safety results from the HAVEN clinical programme.”
Second interim analysis: Surgery
Thirty-one minor surgeries were performed in 22 participants. Of these, 20 were managed without prophylactic coagulation factor, of which three required postoperative treatment for bleeds. Of the 11 procedures managed with prophylactic coagulation factor, only one required postoperative treatment for bleeds. [ISTH 2021, abstract PB0939]
Eight of the nine major surgeries were managed with prophylactic coagulation factor, resulting in four treated postoperative bleeds and two untreated bleeds. The other two had no bleeds.
“[These findings show that in this patient setting,] most minor procedures were performed without prophylactic coagulation factor and did not result in postoperative treated bleeds. Major surgeries were safely performed with additional coagulation prophylaxis,” said the researchers.
Final safety analysis
After a median duration of 103.1 weeks, most participants had zero treated bleeds (83 percent; mean ABR, 0.5). The ABR aligns with those observed in the HAVEN studies. There were no new thromboembolic events since the two reported in the second interim analysis. [ISTH 2021, abstract PB0521]
ADA development was low (n=10) and did not affect the safety or efficacy of emicizumab. None led to a treated bleed or a reduction in emicizumab plasma concentration. Moreover, the ADAs waned over time, with all participants testing ADA-negative at the last visit.
The one case of death reported was deemed unrelated to emicizumab. This adds to the other fatality reported during the first interim analysis, also emicizumab-unrelated, totalling two deaths over the course of the trial.
Taken together, the findings boost the favourable safety and efficacy profile of emicizumab in this patient setting.