Sutacimig, a novel bispecific antibody for prophylactic treatment of glanzmann thrombasthenia: Analysis of a Phase 2 study

Abstract

Abstract Background: Sutacimig is a bispecific antibody designed to bind and accumulate endogenous factor VIIa (FVIIa) and localize it to activated platelets via TLT-1, thereby enhancing thrombin generation at sites of vascular injury. Glanzmann thrombasthenia (GT) is a severe genetic bleeding disorder characterized by deficient or dysfunctional expression of αIIbβ3 integrin, resulting in impaired platelet aggregation and frequent bleeding episodes. No prophylactic therapy exists, leading to substantial morbidity including iron deficiency anemia, heavy menstrual bleeding, and impaired quality of life. Early results from this study evaluating sutacimig as prophylactic therapy for GT demonstrated encouraging safety and >50% reduction in the median annualized treated bleeding rate (ATBR) (Sivapalaratnam, EAHAD & ISTH, 2025). Here, we present interim results from the fully enrolled Phase 2 study (NCT06211634); complete results will be presented at ASH. Methods: We conducted a multicenter, open-label study evaluating prophylactic subcutaneous sutacimig in adults (18-67 years) with confirmed GT. Following completion of the single ascending dose module the multiple ascending dose (MAD) module opened. Treated bleeding events were prospectively recorded in a 6-week run-in period; subsequently, participants received sutacimig for 12 weeks with option to continue in a long-term extension. The primary endpoint in the MAD was safety, with additional endpoints including pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy based on ATBR reduction. Results: As of data cutoff on May 23, 2025, the MAD was fully enrolled with n=34 participants; median age 40.5 years, 47% female. Participants were enrolled into four dosing regimens: 0.3 mg/kg Q2W (n=11); 0.6 mg/kg Q2W (n=13); 0.9 mg/kg Q2W (n=5); 0.3 mg/kg Q1W (n=5). Median exposure in the MAD plus long-term extension was 3.2 months (range 1.7-11.3). AEs were reported in 82% of participants with the majority of AEs graded as mild to moderate. The most common reported AEs (≥10%) were headache (18%), nasopharyngitis (18%), D-dimer elevation (18%), dizziness (12%), and fatigue (12%). Neutralizing anti-drug antibodies developed in 4/34 participants; 2/4 resolved with continued dosing without clinical sequelae. A DVT (Grade 2) was observed in one participant in the 0.9 mg/kg Q2W cohort who discontinued due to this AE. Dosing in this cohort was subsequently suspended. The event is resolving with outpatient treatment. PK and PD (FVIIa) demonstrated a dose-proportional increase with FVIIa accumulation of ~2-4 fold above baseline at ongoing dose levels (0.3-0.6 mg/kg). Interim efficacy analyses demonstrated sutacimig achieved >50% reduction in median ATBR compared to run-in period. Conclusions: In this interim analysis, sutacimig was well tolerated at ongoing dose levels (0.3-0.6 mg/kg) with evidence of clinical activity, with a >50% reduction in median ATBR with sutacimig prophylaxis. Updated safety and efficacy analyses will be conducted following completion of 12-week follow-up for all participants. These data are expected to inform dose selection and support planning for a Phase 3 trial evaluating prophylactic sutacimig for GT.