- Promising efficacy and safety profiles were observed in prior Phase II studies in acute ischemic stroke patients treated with recanalization therapies.
- The ENIS-3 trial has achieved >33% of target enrollment (948 patients). The independent data monitoring committee (IDMC) has completed interim analysis and indicated that the trial should continue.
- The RODIN trial has achieved >45% of target enrollment (496 patients) in 7 months.
YONGIN, South Korea, Sept. 19, 2022 (GLOBE NEWSWIRE) — GNT Pharma Inc. announces that the independent data monitoring committee (IDMC) for ENIS-3 (Efficacy and safety of Nelonemdaz for Ischemic Stroke) has completed a pre-specified interim analysis encompassing 227 acute ischemic stroke patients treated with placebo or nelonemdaz within 8 hours of onset in China. The IDMC concluded that the ENIS-3 trial should continue as planned without modification.
In the prior phase II trial in China (ENIS, 237 patients), administration of nelonemdaz reduced disability primarily in moderate to severe ischemic stroke patients treated with a thrombolytic drug. The ENIS-3 trial was then designed to examine the efficacy and safety of nelonemdaz in 946 patients with moderate to severe acute ischemic stroke treated with tPA within 8 hours of stroke onset.
In South Korea, another multicenter, double-blinded phase III trial (RODIN: Rescue on Reperfusion Damage in Cerebral Infarction by Nelonemdaz) has been initiated to further explore the functional and neuroprotection efficacy of nelonemdaz in acute cerebral ischemia and reperfusion, aiming to enroll a total of 496 patients with moderate to severe ischemic stroke who receive endovascular thrombectomy within 12 hours of stroke onset. The RODIN trial has now enrolled more than 224 patients over the last 7 months and is expected to complete enrollment in the middle of 2023.
In the prior phase II study published online in the peer-reviewed journal Stroke in September, nelonemdaz treatment was associated with better functional outcomes than placebo in moderate to severe ischemic stroke patients who received endovascular thrombectomy within 8 hours of stroke onset. Good functional outcomes were analyzed by a fraction of 0 (no disability symptoms) – 2 (slight disability, able to look after own affairs without assistance) on the modified Rankin Scale (mRS) and a Barthel index of >90 (functional independence in activities of daily living) at 12 weeks. An mRS score of 0–2 was achieved in 54.1% (33/66) and 63.2% (36/57) patients in the placebo and high-dose groups treated with 5,250 mg nelonemdaz, respectively. The common odds ratio (90% confidence interval) indicating a favorable shift in mRS scores was 1.61 (0.94–2.76) between the placebo and high-dose groups. A Barthel index of >90 was observed in 24 (43.6%) and 34 (63.0%) patients in the placebo and high-dose groups, respectively. An overall trend towards excellent outcome (mRS score of 0 and BI of >90) and reduced mortality at 12 weeks, was observed in the nelonemdaz treatment groups compared to placebo.
Dr. Dennis W. Choi, Professor of Neurology, Stony Brook Medicine, and a pioneer in identifying pathological mechanisms of ischemic brain injury said, “Phase III studies of nelonemdaz appear to be progressing well. These trials represent a key shot on the worldwide goal of developing an effective neuroprotective treatment for ischemic stroke.”
Nelonemdaz is a multi-target neuroprotectant acting as both a moderate NR2B-selective N-methyl d-aspartate (NMDA) receptor antagonist and a potent spin trapper that ameliorates both fast NMDA receptor-mediated neuronal death and the delayed free-radical mediated brain cell degeneration occurring hours-to-days after ischemic stroke. In animal models of stroke, superior safety and efficacy was observed for nelonemdaz treatment compared with NMDA antagonists or antioxidants alone.
In prior phase I and phase II studies, administration of nelonemdaz was well-tolerated, with no appearance of the psychotic symptoms seen in humans exposed to previous NMDA receptor antagonist drugs.
“Recent advances in recanalization therapy remarkably improve functional outcomes after acute ischemic stroke and open up new opportunities for neuroprotection therapy based on early delivery and reperfusion,” said Dr. Byoung Joo Gwag, founder and CEO of GNT Pharma. “Nelonemdaz is safe and shows promising efficacy profiles in patients receiving thrombolytic or endovascular therapy. When combined with recanalization therapies, nelonemdaz will hopefully break new ground in treating ischemic brain injury, reducing consequent disability and mortality.”
Nelonemdaz is a breakthrough multi-target neuroprotectant drug candidate, acting both as a moderately powerful, NR2B subtype-selective NMDA receptor antagonist, and a powerful antioxidant. It is designed to safely ameliorate NMDA receptor-mediated excitotoxicity while also reducing free radical toxicity, two major routes of brain cell death after stroke.
About the phase II ENIS Results
In China, a phase II study of nelonemdaz (ENIS trial) has been completed in acute ischemic stroke patients receiving a thrombolytic drug within 8 hours of stroke onset (n=237). Administration of nelonemdaz for 5 days was well-tolerated and showed promising efficacy in moderate to severe stroke patients with initial National Institutes of Health Stroke Scale (NIHSS) scores of ≥6 on admission. The fraction of recovery to normal in placebo-treated group was 13%, 16%, and 26% at 14 days, 30 days, and 90 days, respectively, which improved to 25%, 34% and 44% in the group treated with high dose nelonemdaz.
About the phase II SONIC Results
In South Korea, a phase II, double-blind, randomized, placebo-controlled, multi-center study (SONIC trial) has been conducted to assess the safety and efficacy of nelonemdaz in acute ischemic stroke patients treated with endovascular recanalization within 8 hours of stroke onset.
SONIC enrolled 208 acute ischemic stroke patients with NIHSS score of ≥8. Patients randomly received infusions of placebo, 500 mg nelonemdaz (low-dose group), or 750 mg nelonemdaz (high-dose group) prior to thrombectomy. Low-dose and high-dose nelonemdaz groups then received 9 consecutive infusions of 250 mg and 500 mg every 12 hours, respectively. The primary outcome was the percentage of patients achieving at least a good functional outcome 12 weeks later. Good functional outcome was defined as 0 (no disability symptoms) – 2 (slight disability, able to look after own affairs without assistance) on the modified Rankin Scale (mRS), the most widely used outcome measure in stroke research. In the full analysis set encompassing 183 patients, an mRS score of 0–2 at 12 weeks was achieved in 54.1% (33/66), 61.5% (40/65), and 63.2% (36/57) patients in the placebo, low-dose, and high-dose groups, respectively. In secondary outcomes, the common odds ratio (90% confidence interval) indicating a favorable shift in mRS scores at 12 weeks was 1.55 (0.92–2.60) between the placebo and low-dose groups and 1.61 (0.94–2.76) between the placebo and high-dose groups. A Barthel index of >90 (functional independence in activities of daily living) at 12 weeks was observed in 24 (43.6%), 34 (54.8%), and 34 (63.0%) patients in the placebo, low-dose, and high-dose groups, respectively.
An overall trend towards excellent outcome (mRS score of 0 and BI of >90) and reduced mortality at 12 weeks, was observed in the nelonemdaz treatment groups compared to placebo. No serious adverse events were observed in nelonemdaz treatment groups. The SONIC trial results have been published in the journal Stroke in September.
About the phase III ENIS-3 Trial
Based upon the encouraging results observed in the ENIS trial, Apeloa Pharmaceutical of Hengdian Group, GNTP’s Chinese partner, initiated in December 2020 an ongoing phase III study of nelonemdaz in 948 patients with moderate to severe (9≤NIHSS≤22) acute ischemic stroke (ENIS III), engaging 40 Chinese university stroke centers. All patients receive a thrombolytic drug tPA prior to administration of placebo or nelonemdaz within 8 hours of stroke onset.
About the phase III RODIN Trial
In September 2021, the Korea Ministry of Food and Drug Safety (MFDS) approved an Investigational New Drug Application (IND) for a phase III study of nelonemdaz in acute ischemic stroke patients (RODIN trial). RODIN is designed to investigate the safety and efficacy of 5,250 mg nelonemdaz in 496 patients with severe ischemic stroke receiving endovascular thrombectomy within 12 hours of stroke onset. Patients will be enrolled at 23 university stroke centers and evaluated by mRS, NIHSS, BI, and MRI over 90 days following stroke. At present, RODIN has enrolled 224 patients at 21 university stroke centers including Seoul Asan Medical Center.
About GNT Pharma:
GNT Pharma was founded in April 1998 by eight professors in the fields of neuroscience, pharmacology, medicinal chemistry, psychology, ophthalmology, and cell biology who had all been investigating mechanisms of neuronal cell death. Since then, GNTP has discovered and developed several innovative drug candidates for the treatment of nervous system disorders such as stroke and Alzheimer’s disease.
This press release includes forward-looking statements about GNT Pharma’s efforts to treat acute ischemic stroke and the investigational anti-stroke drug nelonemdaz that are based on management’s beliefs and assumptions, expectations, estimates, and projections as well as facts and factors currently known by GNT Pharma. Statements included in this release that are not historical data and facts, including the words “plans”, “expects”, or similar expressions and statements constitute forward-looking statements.
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