October 14, 2020
GNT Pharma Reports Results From Phase 2 SONIC Study of Nelonemdaz for Acute Ischemic Stroke Patients Treated With Endovascular Thrombectomy
October 14, 2020—GNT Pharma Inc., a South Korea–based developer of drug and technology for the treatment of patients with neurological and inflammatory diseases, reported top-line results from the phase 2 SONIC study assessing the safety and efficacy of nelonemdaz in acute ischemic stroke patients treated with endovascular thrombectomy within 8 hours of symptom onset.
The double-blind, randomized, placebo-controlled, multicenter study demonstrated that the addition of nelonemdaz to endovascular blood clot removal improved a patient’s chances of returning to functional independence 90 days later.
Nelonemdaz is a moderate NR2B-selective N-methyl d-aspartate (NMDA) receptor antagonist and potent spin trapper that reduces NMDA receptor–mediated excitotoxicity and oxidative stress.
According to the company, nelonemdaz previously showed better efficacy and a longer therapeutic time window than subtype-unselective NMDA antagonists or antioxidants alone in five animal models of stroke. Its safety and tolerability in humans has been established in two earlier phase 1 studies conducted in 165 healthy young and elderly volunteers in the United States and China.
The SONIC study enrolled 209 moderate to severe ischemic stroke patients (National Institutes of Health Stroke Scale ≥ 8) at seven university stroke centers in South Korea. Patients received a first infusion of placebo, 500-mg nelonemdaz (low-dose group), or 750-mg nelonemdaz (high-dose group) before thrombectomy. Low-dose and high-dose groups then received nine follow-up infusions of 250-mg and 500-mg nelonemdaz, respectively, at 12-hour intervals.
The primary outcome was the fraction of patients with good functional outcome (no more than slight disability, able to look after own affairs without assistance) at 90 days after treatment, defined as a score of 0 to 2 on the modified Rankin Scale (mRS).
GNT Pharma stated that in the low-dose nelomendaz group, 33 of 55 patients (60%) achieved good functional outcome, and in the high-dose nelomendaz group, 31 of 49 patients (64.6%) achieved good functional outcome, compared with 25 of 49 patients (51%) in the placebo group.
The fraction of patients achieving near-complete recovery (mRS score, 0) was markedly increased in nelonemdaz-treated groups, with 23.6% of the low-dose group and 33.3% of the high-dose group achieving no significant disability 90 days later, compared with only 8.2% of the placebo group. No serious adverse events of nelonemdaz were observed.
Dennis W. Choi, MD, Professor of Neurology at the State University of New York, Stony Brook, in Stony Brook, New York, who specializes in the field of stroke neuroprotection and serves as a scientific advisor to GNT Pharma, commented in the company’s press release, “These are very encouraging phase 2 results that heighten interest in seeing the results of larger phase 3 trials.”
Byoung Joo Gwag, PhD, CEO and Founder of GNT Pharma and inventor of nelonemdaz summarized the findings in the company’s announcement, stating, “Compared to placebo, administration of nelonemdaz increased the chances of achieving a good functional outcome by more than 20% in moderate to severe ischemic stroke patients who received endovascular thrombectomy. And it more than tripled chances of achieving a near-complete recovery.”
Dr. Gwag continued, “Over the last 3 decades, many NMDA antagonists and antioxidant drugs have failed in clinical stroke trials, despite showing efficacy in animal models of stroke. Such failed trials were probably due to the adverse effects of subtype-unselective NMDA receptor antagonists or the limitations of targeting single injury mechanisms. SONIC was the first clinical trial of our novel multitarget neuroprotectant, nelonemdaz, administered to ischemic stroke patients who also received endovascular recanalization, which has recently become a standard of stroke care.”
In a companion phase 2 study with 237 acute ischemic stroke patients conducted in China, nelonemdaz was well tolerated and benefitted patients who were treated with thrombolytic drugs within 8 hours of symptom onset. A phase 3 study of nelonemdaz for 948 ischemic stroke patients treated with a thrombolytic drug has just begun in China, advised GNT Pharma.