RNS60 safe, well tolerated in EAP for advanced ALS
Study supports treatment as option for late-stage disease
RNS60 was well tolerated when inhaled twice daily at home as part of an expanded access program (EAP), and it could be a safe option for people with advanced amyotrophic lateral sclerosis (ALS), a study suggested.
“This EAP supports the safety and tolerability of RNS60,” researchers wrote in “An Expanded Access Protocol of RNS60 in Amyotrophic Lateral Sclerosis,” which was published as a short report in Muscle & Nerve. Revalesio, which is developing RNS60 for ALS, provided the treatment at no cost for the study.
Patients could join the EAP, which is ongoing at Massachusetts General Hospital in Boston, regardless of how long they had the disease or whether they needed a ventilator for breathing or a feeding tube for eating.
EAPs, designed to provide treatment access to patients with serious or life-threatening conditions who would not generally be eligible for clinical trials, “can be leveraged to collect long-term safety data in a broad population,” wrote the researchers, two of whom work at Revalesio. The RNS60 EAP involves patients at advanced stages of ALS, a progressive disease that occurs due to inflammatory damage to motor neurons, the nerve cells that control voluntary movements.
RNS60 is a saline solution rich in oxygen that can be inhaled by nebulization or infused into the bloodstream. It has been shown to reduce inflammation sustained by microglia, immune cells in the brain that help support the function of nerve cells but are overactive in ALS.
Preclinical data showed that RNS60 protected motor neurons from damage in a mouse model of ALS. In a Phase 2 clinical trial (NCT03456882), adding RNS60 to the standard of care extended the survival of people with ALS by a median of about six months compared with a placebo.
For the EAP, patients who were not eligible for clinical trials of RNS60 used a nebulizer at home to inhale 4 mL of RNS60 twice daily, for a total of 8 mL. Patients on non-invasive ventilation or who had undergone a tracheostomy to help with breathing received RNS60 through a special adapter connected to their devices, with help from clinical staff.
The goal was to provide the experimental treatment and collect safety data on a regimen that involves nebulized inhalation twice daily, instead of the regimen used in clinical testing, which involved daily nebulized inhalation along with a weekly infusion into the vein.
Up to the study’s submission, 84 patients with a mean age of 62.2, at advanced stages of disease, had used RNS60 for up to four years. Most (82%) complied with the twice-daily regimen. Twelve (14.3%) stopped due to side effects including breathing problems (four), personal choice (three), and increased secretions (two). Three later resumed full dosing. Two (2.9%) reduced to once-daily dosing.
There were 69 serious side effects in 38 patients. All were due to disease progression, not RNS60, according to the researchers. The most common of these was respiratory failure, leading to death in 24 patients (28%). The most common treatment-related side effect was increased secretions (32%), “which may be due either to the twice-daily dosing regimen or the advanced disease stage,” the researchers wrote.
While the study involved few patients and had no placebo group for comparison, it “supports the safety and tolerability of RNS60 dosed via nebulization twice a day in a population in advanced stages of the disease,” the researchers wrote.
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