Abstract Body: Sovateltide is a synthetic analog of ET-1 and has very high selectivity for ET-B receptors, which are in high concentration in the CNS. Sovateltide induces ET-B receptor-mediated signaling to produce significant anti-oxidative activity, antiapoptosis, mitochondrial fusion and biogenesis, angiogenesis, tissue re-perfusion, neuronal differentiation, tissue regeneration, and repair in the CNS, and a significant recovery in neurological and motor functions and a reduction in the infarct volumes. Studies in mice, rats, and dog models indicate that sovateltide is well tolerated and has a good safety margin.
Clinical studies were conducted to determine human safety and efficacy. Standard of care was provided to all the patients. The study drug was administered in three doses as an intravenous injection over 1 minute at an interval of 3±1 hours on days 1, 3, and 6. Patients received either saline or sovateltide (0.3 µg/kg) within 24 hours of the stroke onset.
In the phase I clinical trial, conducted in healthy individuals, sovateltide had a short half-life of about 5 minutes and was safe and well tolerated. A phase II study was conducted on 40 patients with acute ischemic stroke. An improvement of ≥2 points on the mRS from baseline was observed in 60% and 40% of patients in the sovateltide and saline groups, respectively (p=0.0519; odds ratio 5.25). Phase III study was conducted in 158 acute ischemic stroke patients, of which 78 were in control, and 80 were in the sovateltide group. The data not available (6.4%) were assessed as "missing values" and were imputed using “MICE” by creating multiple imputations. The number of patients with mRS of 0-2 at 90 days was 53.58% in control and 76.25% in the sovateltide groups (p=0.0031). The number of patients with NIHSS of 0-5 at 90 days was 67.95% in control and 85.00% in the sovateltide groups (p=0.0114). The ordinal shift in mRS from 0-1 showed an absolute increase of 8% in the favorable outcome of sovateltide compared to the control group, while a shift in mRS from 0-2 showed an absolute increase of 22% in the favorable outcome of sovateltide compared to the control group.
Pharmacologically targeting ET-B receptors with sovateltide is safe and effective in improving neurological outcomes in cerebral ischemic stroke patients.