Pharmazz, the developer of the endothelin-B receptor agonist, noted that it plans to move forward with an investigational new drug submission to the FDA for sovateltide.
Anil Gulati, MD, PhD, chairman and CEO, Pharmazz, and adjunct professor, Midwestern University
Anil Gulati, MD, PhD
New interim data from a 30-day analysis of 2 multicentric, randomized, blinded, controlled efficacy clinical trials—a phase 2 study (NCT04046484) and a phase 3 study (NCT04047563)—in patients with acute ischemic stroke suggest that sovateltide (PMZ-1620; Pharmazz) effectively improves modified Rankin Scale (mRS) scores compared to standard of care.
The endothelin-B receptor agonist significantly improved mRS scores for those with acute cerebral ischemic stroke when compared to patients receiving the best standard of care (P = .0157; t = 2.476; df = 70). Additionally, mRS scores in patients receiving sovateltide (n = 35) had a difference of means of 2.40 (95% CI, 1.99­—2.80) while the control group (n = 37) had a difference of means of 1.64 (95% CI, 1.22–2.07).
Pharmazz noted in the announcement that “since [the] FDA recommended, in our pre-IND meeting, to keep mRS as the primary end point, we are encouraged by these results and planning to move forward with IND submission to the FDA.” The agent has the potential to be a first-in-class neuronal progenitor cell therapeutic, which Pharmazz believes could significantly improve neurological outcome in patients with acute cerebral ischemic stroke.
In the trials, which were conducted by Anil Gulati, MD, PhD, chairman and CEO, Pharmazz, and adjunct professor, Midwestern University, and colleagues, sovateltide was administered intravenously within 24 hours after the onset of stroke. There were no incidence of treatment-related adverse events (AEs) reported.
Additionally, sovateltide treatment resulted in National Institutes of Health Stroke Scale (NIHSS) improvements (difference of means, 7) compared to the control group (difference of means, 6.23). Similarly, Barthel Index (BI) scores also improved with sovateltide treatment (difference of means, 47.36) compared with control (difference of means, 42.30). Although, these improvements did not reach the level of statistical significance.
“In addition, the Company is continuing multicentric, randomized, double-blind, parallel, saline controlled clinical trials using sovateltide in Alzheimer's disease (NCT04052737) and acute spinal cord injury (NCT04054414). Both studies have crossed 50% of enrollment,” Pharmazz noted.
The phase 2 assessment (NCT04046484) evaluated 40 patients with cerebral ischemic stroke, of which 36 completed the 90-day follow-up. Every patient received standard treatment and were randomized to receive either sovateltide (n = 16) or placebo along with normal saline (n = 18). From baseline to Day 6 of treatment, an improvement of ≥6 in the NIHSS was observed in 87.50% of the intervention arm and 12.50% in the placebo arm (P = .0201). When looking at mRS, a significance value of P = .0859 was observed in the placebo group, compared to P <.0001 in the treatment cohort. Those in the sovateltide cohort experienced a significant improvement (P <.0001) in BI on Day 6 compared to placebo (P = .3948).2
Additionally, after 90 days, 36% and 64% of subjects in the control and sovateltide cohorts, respectively, demonstrated an improvement of ≥40 (P = .0112). An improvement of ≥2 in the mRS was observed in 39.13% and 60.87% subjects in placebo and treatment arms, 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 also greater in the sovateltide cohort compared to placebo.
The first patient was dosed in the phase 3 trial (NCT04047563) on November 10, 2019, and since more patients have been enrolled. Investigators are still actively recruiting patients for the study. It is expected to enroll 110 patients who will be randomly assigned to receive 3 doses of sovateltide via intravenous bolus over a 6-day period plus best available standard of care, or 3 doses of equal volume normal saline plus best available standard of care over the same period. Sovateltide will be administered as an intravenous bolus over 1 minute every 3 (±1) hours on Days 1, 3, and 6 (total dose/day: 0.9 ug/kg body weight).3
1. Sovateltide significantly (p=0.0157) improved clinical outcome (modified Rankin Scale) in patients with acute cerebral ischemic stroke when compared to standard of care [press release]. Willowbrook, IL: Pharmazz; Published July 18, 2019. Accessed May 12, 2020. prnewswire.com/news-releases/sovateltide-significantly-p0-0157-improved-clinical-outcome-modified-rankin-scale-in-patients-with-acute-cerebral-ischemic-stroke-when-compared-to-standard-of-care-301047954.html
2. PMZ-1620, an Endothelin-B Agonist, enters Phase III Trial in Patients with Cerebral Ischemic Stroke [news release]. Willowbrook, IL: Pharmazz; Published July 18, 2019. Accessed May 12, 2020. biospace.com/article/releases/pmz-1620-an-endothelin-b-agonist-enters-phase-iii-trial-in-patients-with-cerebral-ischemic-stroke
3. Dosing of first patient in phase 3 pivotal study of sovateltide (PMZ-1620), a first-in-class investigational product, for acute cerebral ischemic stroke [news release]. Willowbrook, IL: Pharmazz; Published November 23, 2019. Accessed May 12, 2020. biospace.com/article/releases/dosing-of-first-patient-in-phase-3-pivotal-study-of-sovateltide-pmz-1620-a-first-in-class-investigational-product-for-acute-cerebral-ischemic-stroke.