Topline results from the RESCUE trial indicate that RNS60, an anti-inflammatory agent, demonstrates safety and potential efficacy in acute ischemic stroke.
Topline data from the phase 2 RESCUE clinical trial (NCT04693715) showed that RNS60 (Revalesio), an anti-inflammatory and cytoprotective agent, was proven to be safe in patients with acute ischemic stroke (AIS), with results showing potentially critical impacts on reducing poststroke disability.1
Presented in a late-breaking session at the 2024 International Stroke Conference (ISC), held February 7-9, in Phoenix, Arizona, the study randomly assigned 82 participants with AIS to intravenous RNS60 0.5 mL/kg/h (low dose), RNS60 1.0 mL/kg/h (high dose), or placebo starting before completion of endovascular thrombectomy. At 48 hours, the therapy met its primary end point of safety and mortality, with similar rates of serious adverse events (AEs) and numerically lower rates of mortality (with no statistical comparison).
"RNS60’s topline results are very encouraging and suggest the possibility of RNS60 having a profound impact on reducing disability following a stroke," Bert van den Bergh, executive chairman on the board of directors, Revalesio, said in a statement.1 "Revalesio has been developing and testing novel applications of physics in many different biological systems and has seen activity in a wide range of disease models. The novelty of applying physics to biology compelled me to bring my experience in drug development and commercialization to Revalesio."
RESCUE, a multicenter, blinded trial, included participants with a National Institute of Health Stroke Scale (NIHSS) score greater than 5, an ASPECTS score greater than 5, evidenced presence of penumbra/collaterals, and a pre-stroke modified Rankin Scale (mRS) score of 2 or less. Patients were randomized 1:1:1 with block urn randomization to balance age, NIHSS, and ASPECTS.
In addition to meeting its primary end point, treatment with high-dose RNS60 resulted in significantly lowered infarct growth by 50% (nominal P <.05) when compared with placebo based on imaging done at 48 hours. The high-dose active treatment group also outperformed placebo in number of secondary end points, including mRS score at day 90, Barthel Index at day 90, and NIHSS at each specified time point for both absolute value and change from baseline.
"Stroke is the leading cause of disability and death worldwide and carries an enormous financial burden on the health care ecosystem,” David Liebeskind, director of the UCLA Stroke Center, said in a statement.1 "RESCUE was a well-designed and successfully executed Phase 2 trial and it showcases the potential for adjunctive therapies in stroke. I congratulate the investigators and Revalesio on this early data and look forward to seeing RNS60 in a Phase 3 trial."
RNS60 is currently being developed in several other neurologic conditions outside of stroke, including amyotrophic lateral sclerosis (ALS), Alzheimer disease, Parkinson disease, multiple sclerosis, and traumatic brain injury. Although at a molecular level, the mechanism of action of RNS60 has not been fully elucidated yet, its immunomodulatory and cytoprotective properties have been demonstrated in animal models of neuroinflammation, neurodegeneration, and brain injury.
A previously conducted phase 2 study of RNS60 in patients with ALS highlighted the agent’s positive effects on measures of respiratory and bulbar function. Published in the European Journal of Neurology, the study featured patients with definite, probable, or probable laboratory-supported ALS who were assigned to RNS60 (n = 74) or placebo (n = 73) for 24 weeks, followed by an additional 24 weeks off-treatment. While the therapy failed to show an effect on selected biomarkers of inflammation and neurodegeneration, the mean rate of decline in forced vital capacity (FVC) was slower in the RNS60 arm (difference, 0.41 per week; SE, 0.16; P = .0101).2
Additional findings from the study showed that treatment with RNS60 had a significant impact on the eating and drinking domain of the ALS Assessment Questionnaire-40 (difference, –0.19 per week [SE, 0.10]; P = .0319). In a post-hoc analysis, neurofilament light chain increased over time in bulbar onset patients on placebo whilst remaining stable in those treated with RNS60.
"Having our Phase 2 data selected as a late-breaking oral presentation at one of the most prestigious stroke meetings underscores the strength and quality of our results from RESCUE," Greg Archambeau, president of Revalesio, said in a statement.1 “With these data, we are confident in our ability to design and run a robust and properly powered Phase 3 study."