CNM-Au8 Slows Disease Progression in Limb, Bulbar Onset ALS
CNM-Au8, an investigational disease-modifying therapy for people with early amyotrophic lateral sclerosis (ALS), showed consistent clinical benefits in patients with both limb and bulbar onset disease, according to new analyses of RESCUE-ALS Phase 2 clinical trial data.
In particular, the treatment significantly extended the time to disease progression — defined as death from any cause, or the need for tracheostomy, non-invasive ventilation, or a gastrostomy tube — in patients from both groups.
It also was similarly effective at lowering the proportion of patients with a six point or greater decline in their ALS Functional Rating Scale-Revised (ALSFRS-R) scores — indicating loss of functional capacity — after 36 weeks.
Limb onset occurs in about 70% of all ALS patients and is characterized by initial symptoms of muscle weakness or wasting in the arms and legs. In the bulbar onset form of ALS, muscles involved in speaking, swallowing, and breathing are generally the first to be affected.
The findings were presented recently by Robert Glanzman, MD, chief medical officer at Clene, at the 4th Annual ALS ONE Research Symposium, held virtually Nov. 30. His presentation was titled, “Revolutionizing Drug Development for Neurodegenerative Diseases.”
CNM-Au8 is a suspension of nanocrystalline gold designed to promote nerve cell function and survival by boosting energy production in cells, while protecting them from oxidative stress — an imbalance between the production of potentially harmful reactive oxygen species and the body’s ability to eliminate them.
The RESCUE-ALS trial (NCT04098406) involved 45 people with early ALS and assigned them randomly to receive either 30 mg of oral CNM-Au8, or a matching placebo, administered each morning for 36 weeks (about eight months). All patients continued to receive their standard care medications over the trial’s duration.
The study’s main goal was to determine changes in the number, function, and health of motor neurons controlling hand, arm, leg, and feet muscles, using the MUNIX(4) sum, an established predictor of clinical decline.
Secondary measures included changes in lung function, disease progression, the amount of patients experiencing a decline of six or more points in ALSFRS-R, and changes in a combined assessment of ALSFRS-R and survival.
Top-line data from RESCUE-ALS showed that CNM-Au8 was no better than a placebo at preventing motor neuron loss and lung function decline, meaning the trial failed to meet its primary and secondary goals.
Yet, CNM-Au8 demonstrated a significant effect in MUNIX scores at 12 weeks among patients with limb onset ALS, and a trend toward improvement at 36 weeks, with CNM-Au8-treated patients having 45% less loss of motor neurons than those on a placebo. An effect was not observed in bulbar ALS patients because they showed insufficient progression over the trial.
In the recent presentation, the researchers showed the treatment was effective in both patient groups at lowering the risk of disease progression and the amount of patients with at least a six-point decrease in ALSFRS-R.
Other findings showed a trend toward better scores on the combined assessment of ALSFRS-R and survival (CAFS) — meaning potentially less disease progression and greater survival among those receiving CNM-Au8.
People treated with CNM-Au8 showed an average increase in CAFS scores of 4.4 points, while those on a placebo saw their scores decrease by an average of 4.6 points. Due to the small sample size, however, the results failed to reach statistical significance.
“We were pleased to continue sharing our findings from the RESCUE-ALS trial with the ALS community at this symposium, ” Glanzman said in a press release.
“We continue to remain excited about these clinically meaningful findings, which given the remarkable safety and tolerability of CNM-Au8 seen so far in the development program, speak to the potential for a positive benefit-risk assessment,” he added.
After completing the 36-week trial, patients could opt in on an open-label extension part and receive CNM-Au8 for an additional 48 weeks. Results presented at the symposium showed that people on RESCUE-ALS had a trend toward better survival than what would be predicted based on their disease characteristics.
Of note, there were no serious adverse events or treatment discontinuation related to CNM-Au8. The most common treatment-emergent adverse side effects were pneumonia, nausea, and abdominal discomfort, but these were mostly mild to moderate and tended to wear off.