The investigational therapy has the potential to be a first-in-class neuronal progenitor cell therapeutic with anti-apoptotic activity that improves cerebral blood flow and neurological outcome in stroke.
B. Vishwanath Tantry, MBBS, MD, DM,Department of Gastroenterology at KMC Mangalore
B. Vishwanath Tantry, MBBS, MD, DM
As the investigational highly selective endothelin-B receptor agonist PMZ-1620 (IRL-1620; INN sovateltide) moves into a phase 3 trial, it has been found safe in previous phase 1 and 2 human trials.
PMZ-1620 has the potential to be a first-in-class neuronal progenitor cell therapeutic with anti-apoptotic activity, anti-inflammatory, and anti-oxidant activity that promotes the formation of neurogenesis and angiogenesis, improving cerebral blood flow and neurological outcome in cerebral ischemic stroke patients.
The phase 3, multicentric, randomized, double-blind, parallel clinical study will assess the efficacy of PMZ-1620 in addition to the standard of care.
In an earlier phase 2 multicentric, randomized, double-blind, parallel, saline controlled phase 2 study, researchers observed a rapid improvement in clinical outcome in patients treated with PMZ-1620.
The study evaluated 40 patients with cerebral ischemic stroke, of which 36 completed the 90-day follow-up. All patients received standard treatment and were randomized to receive either PMZ-1620 (n=16) or placebo along with normal saline (n=18). PMZ-1620 was administered intravenously within 24 hours of onset of stroke.
Investigators reported a rapid improvement in clinical outcome in subjects treated with PMZ-1620.
From baseline to day 6 of treatment, an improvement of ≥6 in the National Institutes of Health Stroke Scale (NIHSS) was observed in 87.50% (P = .0201) of the intervention arm and 12.50% in the placebo arm. When looking at the Modified Rankin Scale (mRS), a significance value of P = .0859 was observed in the placebo group, compared to P <.0001 in the PMZ-1620 cohort. Subjects in the PMZ-1620 cohort experienced a significant improvement (P <.0001) in the Barthel Index (BI) on day 6 compared to placebo (P = .3948).
At 90 days of treatment, 36% and 64% of subjects in the control and PMZ-1620 cohorts, respectively, demonstrated an improvement of ≥40 in BI (P = .0112). An improvement of ≥2 in the mRS was observed in 39.13% and 60.87% subjects in placebo and PMZ-1620 cohorts, respectively (P = .0519).
The number of subjects with 100% recovery achieving an NIHSS score of 0 (P = .04791), mRS of 0 (P = .1193), and BI of 100 (P = .02795) were greater in the PMZ-1620 cohort compared to placebo.
There was no incidence of drug related adverse effects; treatment with PMZ-1620 did not have an effect on hemodynamic, biochemical, or hematological parameters.
PMZ-1620, an Endothelin-B Agonist, enters Phase III Trial in Patients with Cerebral Ischemic Stroke [news release]. Willowbrook, Ill.: Pharmazz, Inc.; July 18, 2019. https://www.biospace.com/article/releases/pmz-1620-an-endothelin-b-agonist-enters-phase-iii-trial-in-patients-with-cerebral-ischemic-stroke/. Accessed July 24, 2019.