529: SOVATELTIDE (TYCAMZZI) IN PATIENTS WITH CEREBRAL ISCHEMIC STROKE: A RANDOMIZED MULTICENTER STUDY

Abstract

Introduction: Sovateltide (Tycamzzi™) is a novel first-in-class ETB receptor agonist and a synthetic analog of endothelin-1, which promotes neuroprotection, neuroregeneration, and neurovascular remodeling following CNS damage. Methods: A phase III, prospective, multicentric, randomized study was conducted in acute cerebral ischemic stroke (ACIS) patients 18 through 78 years of age. Following radiologic confirmation of ischemic stroke, patients could be enrolled with NIHSS score greater than 5. Excluded were patients with intracranial hemorrhage and those receiving endovascular therapy. Sovateltide was administered in three doses, each dose of 0.3 μg/kg, as an intravenous bolus at an interval of 3 hours ± 1 hour on day 1, day 3, and day 6 (total dose/day: 0.9 µg/kg). The primary objectives were to determine the neurological outcome based on the modified Rankin Scale (mRS) score, National Institute of Health Stroke Scale (NIHSS) score, and Barthel Index (BI) scale score from day 1 through day 90. Results: A significantly (p=0.004) greater number of patients in the sovateltide group (76.1%) had an improvement of mRS of ≥2 points from the baseline compared to the control group (52.8%) at 90 days of treatment. The scores on the mRS at 90 days show an ordinal shift that highly favors sovateltide therapy (56% in control vs. 81% in sovateltide shift in mRS range 0-2). The median score (IQR) of the NIHSS scale at 90 days was 3 (0 to 6) in the control and 1 (0 to 3) in the sovateltide group (p=0.003). An improvement of NIHSS of ≥6 points vs. baseline at 90 days of treatment was significant (p=0.033) in sovateltide (80.6%) compared to the control (64.2%) group. The median score (IQR) of the BI scale at 90 days was 85 (60 to 100) in control and 95 (80 to 100) in the sovateltide group (p=0.01). The number needed to treat (NNT) patients (having mRS of 2 or less at 90 days) with sovateltide was 5 (95% CI 2.6 to 12.2). All-cause mortality was 2.56% in the control and 5.00% in the sovateltide group. Conclusions: Sovateltide demonstrated a statistically significant and clinically meaningful improvement in neurological outcomes in patients with ACIS compared to the standard of care. In addition, sovateltide produced a remarkable ordinal shift in the mRS across the range at day 90 post-randomization.