Cytoprotective Agent RNS60 Receives Fast Track Designation for Ischemic Stroke Treatment

Jordan Dubow

In recent news, the FDA has granted fast track designation to Revalesio’s RNS60, an oxygen-supersaturated saline solution with neuroprotective effects, for the treatment of ischemic stroke. While most stroke care focuses on restoring blood flow, this agent offers a novel, cytoprotective strategy, potentially shielding vulnerable brain tissue even after blood flow is restored.¹

RNS60, a physically modified saline engineered to deliver elevated oxygen levels in tandem with saline, is currently being assessed in a phase 3 study of ischemic stroke, dubbed RESTORE. Backed by preclinical data and previously reported phase 2 evidence showing reduced infarct level and improved functional outcomes, RNS60 has potential to be a leading therapy in stroke-related neuroprotection.

"The Fast Track designation underscores the urgent need for new treatments that go beyond restoring blood flow to actually protect brain tissue and preserve neurological function,” Jordan Dubow, chief medical officer at Revalesio, said in a statement.¹ "We believe RNS60 represents a fundamentally different approach to stroke care, and this designation reinforces the importance of advancing it as quickly as possible."

RNS60’s mechanism of action allows it to support mitochondrial function, enabling cellular energy production, as well as modulate inflammation, especially in glial cells like microglia and oligodendrocytes. In addition, the agent is designed to activate intracellular survival pathways, such as the Type 1A PI3K signaling pathway, which promotes cell resilience, anti-inflammatory responses, and mitochondrial biogenesis.

READ MORE: FDA Denies Approval for Friedreich Ataxia Agent Vatiquinone, Citing More Efficacy Needed

For stroke trials, the drug was previously tested in the phase 2 RESCUE study (NCT04693715), a randomized, double-blind, placebo-controlled trial of patients with acute ischemic stroke due to large vessel occlusion undergoing endovascular thrombectomy (EVT). The trial featured 82 patients who were randomized to either intravenous (IV) RNS60 0.5 mL/kg/h (low dose), RNS60 1.0 mL/kg/h (high dose), or placebo starting before completion of EVT.²

Findings presented earlier this year at the 2025 American Academy of Neurology (AAN) Annual Meeting revealed a 4.8-day reduction in the average amount of time spent in a hospital for those on RNS60 plus standard of care (SOC) vs those on placebo (P = .022). Those in the high-dose cohort demonstrated a 50% attenuation in infarct growth, which was considered statistically significant (P <.05).³

At day 90, outcomes favored the RNS60 high-dose cohort, with 72% achieving functional independence compared with 37% on placebo. This group also showed a 16% higher proportion of patients with an mRS of 0–2 (OR, 3.7; P = .36), along with better measures of daily functioning, including a greater percentage with Barthel Index scores >95 (71% vs 43%; OR, 5.8; P = .13) and higher EQ-5D-5L index values (0.74 [±0.13] vs 0.58 [±0.13]; P = .09). Additionally, patients receiving high-dose RNS60 demonstrated improvements in NIHSS scores compared with placebo, supporting consistent benefit across multiple endpoints.

RNS60 remains in development for other neurologic conditions including amyotrophic lateral sclerosis (ALS) and Alzheimer disease (AD). In a previous phase 2 study of patients with ALS (n = 142), RNS60 showed an ability to help improve respiratory and bulbar function. Over the 24-week treatment period, patients on the agent had slower decline in forced vital capacity compared with placebo (difference, 0.41 per week; P = .0101) and significant improvement in eating and drinking domain of the ALS Assessment Questionnaire (difference, –0.19; P = .0319). Notably, a post-hoc analysis revealed stable levels of neurofilament light chain in bulbar-onset patients with RNS60.³

REFERENCES
1. Revalesio Receives FDA Fast Track Designation for RNS60 for the Treatment of Acute Ischemic Stroke. News release. Revalesio. July 31, 2025. Accessed August 28, 2025. https://www.prnewswire.com/news-releases/revalesio-receives-fda-fast-track-designation-for-rns60-for-the-treatment-of-acute-ischemic-stroke-302517694.html
2. Ghosh S, Dubow J, Sutherland J, et al. RESCUE: A Proof-of-Concept Trial with Adjunct RNS60 Treatment Shows Safety, Reduced Infarct Growth, and Numerical Improvement in all Prespecified Efficacy Endpoints in Participants with Acute Ischemic Stroke. Presented at: 2025 AAN Annual Meeting. ABSTRACT 004832
3. Pupillo E, Bianchi E, Bonetto V, et al. Long-term survival of participants in a phase II randomized trial of RNS60 in amyotrophic lateral sclerosis. Brain, Behav, and Immunity. 2024;122(456-462). doi:10.1016/j.bbi.2024.08.044