RNS60 Treatment Enhances Recovery and Reduces Hospital Stay After Acute Ischemic Stroke

Objective and Background Although reperfusion therapies have improved stroke prognosis profoundly, there remains an unmet need for adjunctive therapies to enhance the brain's resilience to and recovery from a stroke. RNS60 is an experimental cerebroprotective therapy that showed significant efficacy in rodent and non‐human primate (NHP) models of acute ischemic stroke, where it increased survival of neurons under ischemic stress and reduced gliosis. RNS60 provides bioenergetic support to neurons and oligodendrocytes under stress via increased mitochondrial biogenesis and oxidative metabolism. In the proof‐of‐concept Phase 2 RESCUE trial in participants with acute ischemic stroke (AIS) enrolled in <24 hours since last known well (LKW), RNS60 showed preliminary signs of efficacy adjunct to endovascular thrombectomy (EVT) in reduced infarct growth post reperfusion and in multiple Day‐90 functional outcomes. The current post hoc analysis revealed additional benefits of adjunctive RNS60 treatment compared to placebo. Method The multicenter, placebo‐controlled, double‐blind study randomized 82 participants 1:1:1 for age, NIHSS, and ASPECTS to a 48‐hour infusion (RNS60 0.5 mL/kg/h low dose, RNS60 1.0 mL/kg/h high dose, or placebo 1.0 mL/kg/h) starting during EVT. 62 (∼75% of the ITT) of the participants were enrolled in <12h since LKW and were included in this post hoc analysis. The prespecified efficacy endpoints included dichotomized (0‐2, 3‐6) Day‐90 mRS, infarct volume at 48h post‐thrombectomy, BI and EQ‐5D‐5L on Day‐90, and NIHSS at multiple time points. Post hoc analysis also included duration of hospital stay and proportion of subjects discharged to home. Results RESCUE met its primary endpoint of safety and tolerability, with fewer deaths and comparable SAEs in the RNS60 groups compared to placebo. In the ITT population, RNS60 high dose reduced infarct growth (nominal p<.05) and showed numerical improvements for all prespecified efficacy endpoints. In the <12h since LKW subgroup, RNS60 high dose demonstrated greater separation from placebo. The low dose group also showed more consistent numerical benefits than placebo for all efficacy endpoints. Of note, the mean length of hospital stay in the <12h since LKW subgroup was lower by 4.8 days in the participants treated with high dose of RNS60 compared to placebo (p<.05). Also, a higher proportion of participants in the RNS60 high dose group (55.6% compared to 21% in the placebo group, p<.05) was released to home compared to other care facilities. Conclusion Adjunct treatment with RNS60 in <24h since LKW reduced infarct growth and demonstrated numerical improvements in all tested efficacy outcomes. As shown in this post hoc analysis, all effects were more pronounced in participants enrolled in <12h since LKW suggesting further investigation of RNS60 in this population for maximal therapeutic impact.