Abstract 14: A Randomized Study to Determine Efficacy of Sovateltide (PMZ-2010) in Patients With Acute Cerebral Ischemic Stroke

Abstract

Sovateltide (IRL-1620, PMZ-1620), an endothelin-B receptor agonist, administered intravenously following acute cerebral ischemic stroke increased cerebral blood flow, had anti-apoptotic activity and produced neurovascular remodeling. Its safety and tolerability were confirmed in healthy human volunteers (CTRI/2016/11/007509). A prospective, multi-centric, randomized, double-blind, parallel, controlled clinical study to compare efficacy of sovateltide with standard treatment in patients with acute cerebral ischemic stroke (CTRI/2017/11/010654; NCT04046484) was conducted in 40 patients, of which 36 completed 90-day follow-up. Patients received saline (n=18; 11 male and 7 female) or sovateltide (n=18; 15 male and 3 female) within 24 hours of onset of stroke. Standard treatment in both cohorts was similar. Mean age in saline and sovateltide cohorts was 58.34±1.73 and 49.83±2.79 years, respectively. Number of patients receiving investigational drug within 20 hours of onset of stroke were 14/18 in saline and 10/18 in sovateltide cohorts. National Institute of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS) and Barthel Index (BI) on day 6 when compared to day 1 showed P values of 0.0495, 0.0859 and 0.3948, respectively in saline cohort, whereas the P value in sovateltide cohort was less than 0.0001 of all three indices in sovateltide cohort. An improvement of 6 or more in NIHSS at 90 day of treatment was 57% in sovateltide and 43% patients in saline cohort (P=0.2714; Odds ratio 2.275). mRS improvement of 2 or more was observed in 60% and 40% patients in sovateltide and saline cohorts, respectively (P=0.0519; Odds ratio 5.25). BI improvement of 40 or more was 64% and 36% in sovateltide and saline cohorts, respectively (P=0.0112; Odds ratio 12.44). Number of patients with full recovery achieving NIHSS score of 0 and BI of 100 were significantly (P<0.05) more in sovateltide cohort compared to saline. Hemodynamic, biochemical or hematological parameters were not affected and no incidence of drug related adverse event with sovateltide was reported. Sovateltide (PMZ-1620) has the potential to an effective first-in-class drug that promotes quicker recovery and improves neurological outcome in acute ischemic stroke patients.