A new analysis of data from a Phase 2 clinical trial indicates that Revalesio's RNS60, when used as an add-on therapy to standard treatments for amyotrophic lateral sclerosis (ALS), extended the median survival of patients by about six months compared to a placebo. The multi-center trial, conducted across 22 sites in Italy, suggests that RNS60 may offer a clinically meaningful benefit for individuals battling this progressive neurodegenerative disease. The findings, derived from up to six years of follow-up data, were published in the journal Brain, Behavior, and Immunity.
RNS60 and ALS: A Closer Look at the Data
The Phase 2 trial (NCT03456882) involved 147 ALS patients who were randomized to receive either RNS60 or a placebo for six months, in addition to standard riluzole therapy. The primary endpoint focused on assessing the impact of RNS60 on various ALS biomarkers and clinical outcomes. While initial six-month data showed a slower decline in forced vital capacity (FVC) in the RNS60 group, no significant differences in disease progression or survival were observed at that time.
The new post-hoc analysis, with a mean follow-up of 2.8 years, revealed that patients treated with RNS60 lived a median of three years, compared to 2.4 years for those on the placebo. Although this difference did not reach statistical significance in the overall population, further analysis identified subgroups of patients who experienced more pronounced benefits. Specifically, patients with slower FVC decline in the first four weeks of the trial lived significantly longer (median 3.7 years vs. 1.6 years).
Biomarker Insights and Patient Selection
Interestingly, the survival benefits of RNS60 appeared to be influenced by baseline levels of neurofilament light chain (NfL) and monocyte chemoattractant protein-1 (MCP-1). Patients with low levels of these biomarkers at the start of treatment experienced significantly longer survival with RNS60 compared to placebo, suggesting that NfL and MCP-1 levels may help identify which ALS patients are more likely to respond to RNS60.
Letizia Mazzini, MD, professor of neurology and director of the Tertiary ALS Center at the University of Piemonte Orientale in Italy, emphasized the potential of these findings: "These results warrant further investigation, and I look forward to the future development of RNS60 for the treatment of ALS."
Mechanism of Action and Future Directions
RNS60 is an experimental therapy designed to address key mechanisms implicated in ALS, including inflammation, mitochondrial dysfunction, and nerve cell death. Preclinical studies have demonstrated its ability to protect neurons and supporting cells in the brain and spinal cord.
The researchers advocate for a Phase 3 clinical trial to evaluate whether longer administration of RNS60 is associated with slower decline in respiratory function and improved survival in people living with ALS. Revalesio's executive chairman, Bert van den Bergh, stated, "We are committed to advancing RNS60 in additional clinical trials to further evaluate [its] potential to benefit people with ALS and other neurological disorders."
RNS60 has been granted orphan drug and fast track status by the FDA, which could expedite its development and regulatory review for ALS. The original Phase 2 study was supported in part by funding from the ALS Association through the ALS Ice Bucket Challenge.
