NoNo Inc. announced results from the pivotal Phase III ESCAPE-NA1 trial of intravenous nerinetide in patients with acute ischemic stroke who were chosen to undergo endovascular thrombectomy. The drug, without previous administration of alteplase (Genentech’s Activase), provided medically important improvements in the patients. The results were simultaneously presented at the International Stroke Conference in Los Angeles and published in The Lancet.
The pivotal Phase 3 ESCAPE-NA1 study was a multicenter, randomized, double-blinded, placebo-controlled, parallel group, single-dose study designed to evaluate the efficacy and safety of intravenous administration of the novel peptide, nerinetide, in patients with acute ischemic stroke who were selected to undergo endovascular thrombectomy. The trial enrolled 1,105 patients across 48 sites globally including the U.S., Canada, EU, Asia and Australia. Participants were randomized to either a single 2.6 mg/kg dose of nerinetide or placebo immediately following meeting of enrollment criteria, which included enrolling participants within a 12-hour window from stroke onset to randomization, and within 30 minutes of randomization. Alteplase was administered to a subset of patients as per standard of care. The enrolled patient population was stratified into two pre-specified subgroups – patients treated with alteplase and patients not treated with alteplase – because of prior data that showed that alteplase activates plasmin, which cleaves nerinetide and can reduce its plasma levels and thus its potential for efficacy. The primary endpoint was the proportion of patients who achieve functional independence at 90 days after their stroke, defined as 0-2 on the Modified Rankin Scale (mRS; range 0 to 6, with higher scores indicating greater disability).
Nerinetide did not improve the proportion of patients achieving good clinical outcomes after endovascular thrombectomy compared with patients receiving placebo. These findings, which were consistent over three different domains of clinical outcome in patients who did not receive alteplase were bolstered further by pharmacokinetic data from trial participants showing that patients who were treated with alteplase had an approximately 60% reduction in plasma nerinetide levels as compared with patients who did not receive alteplase.
“Results of the ESCAPE-NA1 Phase 3 clinical trial are scientifically groundbreaking because it demonstrates important effects of a pharmaceutical therapy in an acute stroke population treated for up to 12 hours after stroke symptom emergence,” said Dr. Michael Tymianski, president and chief executive officer and founder of NoNO Inc. “Although patients who had prior administration of alteplase did not appear to benefit, likely due to a reduction of nerinetide plasma levels when alteplase was given first, we are excited by the magnitude and consistency of data in the pre-specified subgroup that were not treated with alteplase as well as the potentially long therapeutic window of nerinetide after stroke onset. In addition, nerinetide was well tolerated.”
The study was co-led by Michael Hill, M.D., a neurologist at Foothills Medical Centre (FMC) and professor in the departments of Clinical Neurosciences and Radiology at the Cumming School of Medicine (CSM), University of Calgary and Mayank Goyal, M.D., Ph.D., a neuroradiologist at the FMC, and clinical professor in the Department of Radiology at the CSM, University of Calgary.