Abstract Number: PB0958
Meeting: ISTH 2020 Congress
Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical
Background: Emicizumab, a subcutaneously administered, bispecific monoclonal antibody, bridges activated factor (F)IX and FX, replacing the function of missing activated FVIII in PwHA, thereby restoring hemostasis.
Aims: To provide updated interim results from STASEY (NCT03191799), a study of emicizumab prophylaxis in PwHA with FVIII inhibitors.
Methods: Following ethics committee approval and informed consent, PwHA aged ≥12 years with FVIII inhibitors (N=195; intent-to-treat population) received emicizumab 3 mg/kg/week for 4 weeks, followed by 1.5 mg/kg/week for the remainder of 2 years. The primary objective was safety (adverse events [AEs], including thromboembolic events [TEs], hypersensitivity); secondary objectives included efficacy (annualized bleed rates [ABRs]).
Results: At cut-off (May 20, 2019), 193 PwHA had received emicizumab and were evaluable for safety; median age (range) was 28.0 (12-80) years; median (range) treatment duration was 50.9 (1.1-88.1) weeks. Emicizumab was well tolerated (Table 1). Two AEs were classed as TEs: ST-elevation myocardial infarction (STEMI) (n=1); hypertrophic clot following tooth extraction caused by multiple doses of antifibrinolytic combined with rFVIIa (n=1). The 55-year-old PwHA with STEMI 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. Emicizumab-related AEs were reported in 33 PwHA; injection-site reactions were most common (22/193 PwHA; 11.4%). One fatality was reported (polytrauma), assessed as unrelated to emicizumab. Three PwHA received activated prothrombin complex concentrate and 32 received rFVIIa, with no associated thrombotic microangiopathy or arterial/venous TEs. Ten PwHA (5.2%) developed anti-drug antibodies, none with neutralizing potential (by pharmacokinetic/clinical assessment); they continued on 1.5 mg/kg/week emicizumab with no increased bleeding. ABRs remained low (Table 2 ).
Conclusions: No new safety signals were identified; these data confirm the safety results from the HAVEN clinical program.
| Adverse Event (AE), n (%) | Emicizumab 1.5 mg/kg/week n=193 |
| Total number of AEs | 551 |
| Number of people with hemophilia A (PwHA) with ≥1 event Fatal AE Serious AE AE leading to treatment withdrawal AE leading to dose modification or interruption AE leading to study discontinuation Grade ≥3 AE Study treatment-related AE Injection-site reaction |
145 (75.1) 1 (0.5)* 19 (9.8) 1 (0.5) 3 (1.6) 0 22 (11.4) 33 (17.1) 22 (11.4) |
| AEs of interest Systemic hypersensitivity/anaphylactic/anaphylactoid reaction Thromboembolic event (TE) TE associated with activated prothrombin complex concentrate (aPCC) and emicizumab Thrombotic microangiopathy (TMA) TMA associated with aPCC and emicizumab |
0 0 |
| Most common AEs (≥10% of PwHA) Nasopharyngitis Headache Injection-site reaction |
24 (12.4) 23 (11.9) 22 (11.4) |
| *Polytrauma with fatal head injury, unrelated to emicizumab, previously reported in first interim analysis. One injection-site reaction was manually added, as the AE page may have been incorrectly completed (currently being queried). ST-elevation myocardial infarction due to thrombus in a coronary artery in one PwHA, and hypertrophic clot at site of tooth extraction in one PwHA who was receiving anti-fibrinolytics. The latter is a known complication of tooth extractions. Coded using Medical Dictionary for Regulatory Activities (MedDRA) Version 21.1. |
|
[Table 1: Safety Summary (Safety-Evaluable Population)]
| Annualized bleed rate (ABR)* | Emicizumab 1.5 mg/kg/week N=195 |
| Treated bleeds Mean ABR, model based (95% confidence interval [CI]) Median ABR, calculated (interquartile range [IQR]) People with HA (PwHA) with zero bleeds, n (%) |
0.5 (0.27-0.86) 0.0 (0.00-0.00) |
| All bleeds Mean ABR, model based (95% CI) Median ABR, calculated (IQR) PwHA with zero bleeds, n (%) |
1.3 (0.95-1.80) 0.0 (0.00-1.14) 121 (62.1) |
| Treated spontaneous bleeds Mean ABR, model based (95% CI) Median ABR, calculated (IQR) PwHA with zero bleeds, n (%) |
0.3 (0.13-0.67) 0.0 (0.00-0.00) 179 (91.8) |
| Treated joint bleeds§ Mean ABR, model based (95% CI) Median ABR, calculated (IQR) PwHA with zero bleeds, n (%) |
0.3 (0.12-0.84) 0.0 (0.00-0.00) 182 (93.3) |
| Treated target joint bleeds Mean ABR, model based (95% CI) Median ABR, calculated (IQR) PwHA with zero bleeds, n (%) |
0.2 (0.06-0.68) 0.0 (0.00-0.00) 186 (95.4) |
| *The Bleed and Medication Questionnaire was completed by participants/caregivers via an electronic handheld device. Bleed definitions were based on International Society on Thrombosis and Haemostasis criteria (Blanchette VS, et al., J Thromb Haemost 2014;12:1935-39). Treated bleeds were defined as a bleed directly followed by a hemophilia medication reported as a treatment for bleed, without an intervening bleed and irrespective of the time between the treatment and the preceding bleed. If multiple bleeds occurred on the same calendar day, the subsequent treatment was considered to apply to each of these multiple bleeds. Bleeds due to surgery/procedure are excluded. Calculated using negative binomial regression method. §Joint bleeds are defined as bleeds with type reported at ‘joint’ in combination with ≥1 of the following symptoms: increased swelling or warmth of the skin over the joint; increasing pain; decreased range of motion or difficulty in using the joint compared with baseline. |
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[Table 2: Efficacy Summary (Intent-to-Treat Population)]
To cite this abstract in AMA style:
Jiménez-Yuste V, Santagostino E, Klamroth R, Castaman G, Shanmukhaiah C, Rangarajan S, García Chavez J, Martinez R, Kenet G, Robson S, Schmitt C, Meier O, Ozelo M. Second Interim Analysis Results from the STASEY Trial: A Single-Arm, Multicenter, Open-Label, Phase III Clinical Trial to Evaluate the Safety and Tolerability of Emicizumab Prophylaxis in People with Hemophilia A (PwHA) with FVIII Inhibitors [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/second-interim-analysis-results-from-the-stasey-trial-a-single-arm-multicenter-open-label-phase-iii-clinical-trial-to-evaluate-the-safety-and-tolerability-of-emicizumab-prophylaxis-in-people-with/. Accessed September 27, 2023.« Back to ISTH 2020 Congress
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