PMZ-1620 Enters Phase 3 Trial As a Potential Treatment For Cerebral Ischemic Stroke

July 25, 2019

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

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.

REFERENCE

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.