A gold-based investigational therapy for ALS has failed to show slowing of disease progression in a trial conducted in US specialist centres.

CMN-Au8, a suspension of gold nanocrystals that is said to enhance neuronal energy production and utilisation, was one of three therapies evaluated in the HEALEY ALS Platform Trial led by the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital (MGH).

In the CNM-Au8 arm of the randomised, double-blind trial, 161 patients with with familial or sporadic ALS were randomised to 30 mg CNM-Au8, 60 mg CNM-Au8, or placebo as adjunct to standard of care for a 24-week treatment period.

Preliminary results released by developer Clene Nanomedicine showed the primary endpoint was not met. There was no statistically significant or clinically meaningful slowing of disease progression as measured by ALS Functional Rating Scale-Revised (ALSFRS-R) slope change adjusted by mortality across the combined CNM-Au8 doses at 24 weeks (2% slowing, 95% CI: -20% to +19%).

Also, key secondary endpoints including a combined assessment of function and survival (CAFS) and change in slow vital capacity (SVC) were also not met at week 24.

There was a possible survival benefit, with prespecified exploratory analyses showing a >90% reduction in risk of death alone or risk of death/permanently assisted ventilation at 24 weeks, when adjusting for baseline imbalances in risk (p=0.028 to p=0.075, unadjusted for multiple comparisons) with the CNM-Au8 30 mg dose. However the number of events were small and a survival benefit was not observed among participants randomised to 60 mg CNM-Au8.

The study investigators said an open label extension study will continue at 30 mg/day, and full analyses, including data on measures of speech function, biomarkers of neurodegeneration and further results from the extension, will be released later in 2022.

“Though we did not achieve success on the primary and key secondary outcomes during the 24-week placebo-controlled period of this trial, the potential survival benefit at 30 mg/day dose is encouraging and warrants continued follow up in the open-label extension study. In addition, the digital and fluid biomarker results will provide additional insights into disease biology and drug effects for CNM-Au8,” said study investigator Prof. Merit Cudkowicz, chief of the Department of Neurology at MGH, and director of the Sean M. Healey & AMG Center for ALS.

“We are thankful to the many people who participated in this study. We will learn from these results and continue to use these data to inform future advances in ALS trial design,” he added.

Despite the negative findings, the drug’s developer Clene Nanomedicine said it believed the results supported the rationale for treating neuronal and glial energetic failure with CNM-Au8.

“We have now completed multiple Phase 2 studies in ALS and MS, building a body of evidence demonstrating that CNM-Au8 supports cellular energy production, improving myelination and neuronal viability,” a spokesperson said.

Co-investigator Dr James Berry, Director of the Neurological Clinical Research Center at MGH, said the HEALEY ALS Platform Trial was providing substantial clinical and biomarker data that will help better understand ALS disease mechanisms and the role of cellular catalysts in people living with ALS.

“We remain committed to using the data to advance ALS science and will use our experience with the trial to understand the biology of CNM-Au8, investigate ALS mechanisms, and find novel therapies for people living with ALS,” he said.

As reported recently in the limbic, an Australian trial of  CNM-Au8  – the RESCUE-ALS trial – showed that it helped slow disease progression and functional decline versus placebo and led to better than predicted long-term survival in treated patients.