Sovateltide: A new option to improve neuro outcomes after cerebral ischaemic stroke?

The endothelin-B receptor agonist sovateltide appears to improve neurological outcomes in patients with acute cerebral ischaemic stroke (ACIS), according to a phase III trial presented at WSC 2022.

The study involved 158 patients with ACIS, no intracranial haemorrhage, and not on endovascular therapy who presented within 24 hours of stroke onset. Patients needed to have an NIHSS* score of >5 and mRS** score of 3–4 to be included. In addition to standard of care treatment, the patients were randomized 1:1 to receive intravenous sovateltide (three 0.3 µg/kg bolus doses) or saline (control group) on days 1, 3, and 6.

Median age at baseline was 56 and 59 years in the sovateltide and control groups, respectively, and 66 and 62 percent, respectively, were male. NIHSS score at baseline was 9 and 10 in the sovateltide and control groups, respectively. Patients received treatment a median 19 hours following stroke onset. Fewer patients in the sovateltide than placebo group were on thrombolytic therapy at baseline (11.2 percent vs 25.6 percent). The main types of stroke were large artery atherosclerosis (46 percent vs 37 percent) and small vessel occlusion (36 percent vs 37 percent).

Significantly more patients in the sovateltide than control group experienced a ≥2-point reduction in mRS score by day 90 (76.12 percent vs 52.86 percent; odds ratio [OR], 2.843, 95 percent confidence interval [CI], 1.368–6.015; p=0.0045). [WSC 2022, abstract O307]

At day 90, patients assigned to sovateltide had a significantly lower mRS score than those assigned to the control group (mean 1.48 vs 2.10; p=0.0078), as well as a lower NIHSS score (mean 1.985 vs 3.571; p=0.0024). More patients in the sovateltide than control group had an mRS score of 0–2 at 90 days (80.60 percent vs 55.71 percent; OR, 3.302, 95 percent CI, 1.501–7.044; p=0.0018), as well as a change of ≥6 points in NIHSS score (82.09 percent vs 64.29 percent; OR, 2.546, 95 percent CI, 1.176–5.798; p=0.190).

Exploratory analyses showed that more patients in the sovateltide than control group achieved mRS 0 (26.87 percent vs 15.71 percent) and NIHSS score 0 (37.31 percent vs 25.71 percent) at 90 days. Quality of life, based on the EuroQoL Scale, was also improved in the sovateltide than control group (p=0.0055). However, Montreal Cognitive Assessment at day 90 showed no significant difference between groups (mean 22.64 vs 22.12; p=0.6503).

There were four and two deaths in the sovateltide and control groups, respectively. Adverse events occurred in 15 and 24 patients, respectively. There was one incident of serious hyponatremia in the sovateltide group, and seven patients in each group experienced intracranial haemorrhage.

Prior studies have suggested that intravenous administration of sovateltide had anti-apoptotic activity, increased cerebral blood flow, and produced neurovascular remodelling in animal models with ACIS, said the authors.

“This phase III trial demonstrates practice-changing results with a statistically significant and clinically meaningful improvement in neurological outcomes in ACIS patients,” presented study author Dr Anil Gulati from Pharmazz, Inc, Willowbrook, Illinois, US.