Abstract Background and aims Sovateltide (Tycamzzi®), an endothelin B receptor agonist, is being marketed in India and is undergoing phase 3 clinical trials (RESPECT-ETB) in the USA, Germany, Spain, Australia, and the UK for the treatment of acute cerebral ischemic stroke (ACIS). Alteplase and tenecteplase are widely used to lyse the clot in patients with ACIS. This meta-analysis aims to determine the relative effectiveness of sovateltide to alteplase and tenecteplase in patients with ACIS. Methods A systematic review of studies indexed in PubMed and Google Scholar through June 2025 was conducted using the PICOT framework. Twenty-nine published studies involving 15,696 patients (alteplase: 10,595; tenecteplase: 4,823; sovateltide: 278). Assessment for excellent (mRS 0, 0–1) and good (mRS 0–2, 0–3) functional outcomes at 90 days was conducted. Odds ratios (ORs) were calculated and analyzed for subgroup differences. Results Sovateltide showed outcomes better than alteplase for mRS 0-1 (OR 1.89±0.27 vs. 1.17±0.11; p=0.02), 0–2 (OR 4.87±1.87 vs 1.09±0.11; p=0.0003), and mRS 0–3 (OR 4.78±1.76 vs 1.02±0.16; p=0.0001), and was non-inferior at mRS 0 (OR 1.9±0.27 vs 1.32±0.12; p=0.26). Sovateltide showed similar results with tenecteplase at mRS 0 (p=0.03), 0–1 (p=0.02), 0–2 (p=0.002), and 0–3 (p=0.0002). Patients not receiving thrombolytics, sovateltide had better outcomes at mRS 0 (OR 5.43±2.45 vs 1.32±0.2; p=0.0049). Mortality and intracranial hemorrhage rates were comparable across groups. Heterogeneity was moderate (I2 = 26.8%), and funnel plots showed minimal publication bias. Conclusions Sovateltide demonstrates effectiveness and has promise to treat ACIS patients. (Registration: https://doi.org/10.17605/OSF.IO/P7FNJ). Conflict of interest Anil Gulati and Amaresh Ranjan are employees and stockholder of Pharmazz Inc. No conflicts related to the content of this article are reported by Preyan Mehta
Ranjan et al. (Fri,) studied this question.