Gold results for novel ALS therapy presented at ANZAN 2022

Neurodegenerative disorders

By Natasha Doyle

2 Jun 2022

A gold-based amyotrophic lateral sclerosis (ALS) therapy has had shining results in a phase II trial, giving researchers hope that a “reasonably good” disease challenger might finally be in reach, an Australian neurologist told the ANZAN 2022 meeting.

Professor Steve Vucic, clinical academic and translational researcher at the University of Sydney, Westmead Hospital said the suspension of gold-containing nanocrystals — CNM-Au8 — helped slow disease progression and functional decline versus placebo and led to better than predicted long-term survival in treated patients.

As lead investigator he presented a session at the ANZAN conference on the RESCUE-ALS trial, which assessed the drug’s efficacy and safety in 45 newly-symptomatic (within 24 months of screening) ALS patients over 36 weeks.

It found those on 30 mg once-daily oral CNM-Au8 had significantly slower disease progression — defined as death, tracheostomy, non-invasive ventilation or gastrostomy tube — versus placebo (P = 0.0125) over the study period.

They also had a significantly-reduced rate of functional decline, with nearly 50% of CNM-Au8 patients declining less than six ALS Functional Rating Score-Revised (ALSFRS-R) points in 36 weeks versus nearly 20% in placebo (P = 0.0350).

The 60-week open-label extension period saw treated patients achieve 70% improvement in long-term survival versus the predicted outcome (hazard ratio [HR]: 0.297, 95% CI: 0.128–0.690, P = 0.0068), Professor Vucic reported.

Furthermore, no significant adverse events were reported during the trial, he said.

These “exciting” results have “opened up the avenue now for a much larger phase III study”, he told the limbic.

Currently, riluzole is the only approved therapeutic agent for ALS in Australia and both it and edaravone are FDA approved for use in America, however neither treatment “has resulted in substantial disease modifying effects”, the study protocol, published in BMJ Open noted.

It said the antiglutamatergic agent riluzole extends patient lifespans by mean 2–3 months, while free-radical scavenger edaravone slows the rate of ALSFRS-R score decline “in only a small subset of patients treated at an early stage of disease”.

Unmet clinical need

“There’s really no other effective therapies in ALS that are clinically available,” Professor Vucic said.

While existing and emerging treatments “slow down disease progression somewhat”, “I think [CNM-Au8] is the only medication or compound that I’ve seen that has slowed down functional decline and disease progression.”

“And obviously it’s got to be verified in larger clinical trials, but if verified, it will be very exciting”.

The drug “poses several advantages over small molecule and biologic agent approaches: it has a unique multimodal mechanism of action that can address age and disease-related bioenergetic failure, oxidative stress and proteostasis dysregulation,” the protocol paper read.

It helps reduce bioenergetic failure by catalysing nicotinamide adenine dinucleotide hydride’s (NADH) conversion to NAD+, leading to increased intracellular NAD+ and increased ATP production.

This, combined with its ability to increase proteostatic Heat Shock Factor 1 activity “has been shown to be neuroprotective in ALS disease models”, it explained.

Based on RESCUE-ALS’s outcomes, Professor Vucic expects to start phase III trials toward the end of this year.

“There is hope on the horizon, so stay tuned for the phase III results, because we might [soon] have a reasonably good treatment available,” Professor Vucic concluded.

This study was sponsored by CNM-Au8 manufacturer Clene Nanomedicine and Professor Vucic is a director of a company that holds equity in the Clene Nanomedicine. 

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