RNS60 Extended ALS Survival in Phase 2 Post-Hoc Trial Analysis

Revalesio, a clinical-stage pharmaceutical company specializing in neurological disorder treatments, has recently published promising data in the journal Brain, Behavior, and Immunity. Their investigational therapeutic, RNS60, demonstrated a significant extension in median survival by six months compared to a placebo in a post-hoc analysis of a Phase 2 trial. This trial, sponsored by investigators at the Research Center for ALS, Istituto di Ricerche Farmacologiche Mario Negri IRCCS in Milano, Italy, offers hope for patients suffering from amyotrophic lateral sclerosis (ALS).

The double-blind trial involved a 6-month treatment phase, followed by an average follow-up period of 2.8 years to monitor survival rates. The results were encouraging: the RNS60 treatment group had a median survival of 3 years, whereas the placebo group had 2.4 years (p = 0.0519). Moreover, the trial indicated a slower decline in forced vital capacity (FVC), a crucial measure of respiratory function in ALS patients, for those treated with RNS60. Specifically, at the end of the treatment, the RNS60 group exhibited a significantly slower decline in FVC compared to the placebo group (FVC difference 0.41 per week, standard error 0.16, p = 0.0101).

Further analysis revealed a correlation between extended survival and the rate of FVC decline. Participants with a slower decline in FVC had a median survival of 3.7 years, while those with faster declines had a median survival of 1.6 years (p < 0.0001). Additionally, participants with lower baseline levels of neurofilament light chain (NfL) or monocyte chemoattractant protein-1 (MCP-1) showed a significantly longer survival when treated with RNS60 compared to placebo. NfL and MCP-1 are biomarkers associated with neuronal damage and inflammation, respectively, and their levels are known to increase as ALS progresses. This suggests that targeting patients with low baseline levels of these biomarkers could be beneficial in future studies involving RNS60.

“These findings are encouraging and suggest that RNS60 could positively impact both survival and respiratory function in ALS patients,” said Letizia Mazzini, a Professor of Neurology and Director of the Tertiary ALS Center at the University of Piemonte Orientale. “These results merit further investigation, and we look forward to the continued development of RNS60 for ALS treatment.”

Bert van den Bergh, Revalesio’s Executive Chairman and a former President of Neuroscience Products at Eli Lilly and Company, echoed this enthusiasm. He noted that RNS60 has shown beneficial effects in two randomized clinical trials for ALS and ischemic stroke. “These results underline the potential of RNS60 to benefit patients with acute and chronic neurological disorders,” he said. "We are committed to advancing RNS60 in additional clinical trials to further evaluate its potential."

The Phase 2 trial was a multi-center, randomized, double-blind, placebo-controlled study involving 147 ALS patients across 22 Italian ALS centers. The participants were classified based on the rate of FVC decline during the treatment period, and primary endpoints included safety and biomarker levels related to ALS, while secondary endpoints comprised ALS functional rating scales, FVC, and survival. Following the 6-month treatment phase, participants were monitored for survival, which supported the post-hoc analysis.

RNS60 is an investigational therapeutic designed to offer disease-modifying and potentially restorative treatments for neurological diseases. Preclinical studies indicate that RNS60 activates intracellular signaling pathways to improve mitochondrial biogenesis and function while reducing inflammation. It has been granted Orphan Drug and Fast Track designations for ALS by the U.S. Food and Drug Administration.

Revalesio, headquartered in Tacoma, Washington, continues to push the boundaries in treating acute and chronic neurological disorders, with RNS60 leading their clinical programs. The company’s innovative technology aims to address core mechanisms involved in cellular function, aiming to slow disease progression and enhance the quality of life for patients.