Early CNM-Au8 Treatment Leads to Significant Survival Benefit in Study

70% lower risk of death found in patients originally assigned CNM-Au8 vs. placebo

Marta Figueiredo, PhD avatar

by Marta Figueiredo, PhD |

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Early use of Clene Nanomedicine’s experimental therapy CNM-Au8 reduces the risk of death by 70% in people with amyotrophic lateral sclerosis (ALS), compared with patients who experienced a nine-month delay in starting treatment.

These are the findings of an updated analysis of the RESCUE-ALS Phase 2 trial (NCT04098406) and its open-label extension (OLE) study (NCT05299658), whose previous results only suggested possible trends that favored CNM-Au8.

“We are very pleased to see these results and the apparent survival benefit that our investigational drug, CNM-Au8, appears to provide to people living with ALS,” Rob Etherington, Clene’s president and CEO, said in a press release.

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Clene plans to share these results at an upcoming scientific congress.

“At this point, we are awaiting top-line data from the HEALEY ALS Platform Trial, which focuses on endpoints measuring patient function, survival and breathing over a six-month period in a much larger [group of patients],” Etherington added.

HEALEY (NCT04297683) is evaluating the safety and effectiveness of CNM-Au8 and several other potential ALS therapies, against a shared placebo group.

In the CNM-Au8 arm, about 160 ALS patients were randomly assigned to drink two bottles of either 30 or 60 mg of CNM-Au8 (120 patients) or a placebo (40 patients), daily for about six months.

“Based on the larger number of patients treated in the HEALEY trial and the higher dose of CNM-Au8 being tested, we are optimistic that we will be able to adequately characterize the effects of our drug on this devastating disease,” Etherington said.

Results of CNM-Au8’s six-month Phase 2/3 trial arm (NCT04414345) are expected in coming months. Should they be positive, Clene plans to use them to support regulatory submissions seeking the therapy’s approval for ALS.

CNM-Au8, a stable liquid suspension of pure gold nanocrystals, is designed to improve the survival and function of nerve cells by supporting their energy needs and protecting them against oxidative stress, a type of cellular damage implicated in ALS.

As such, the therapy is thought to prevent nerve cell death and slow disease progression in ALS patients.

The Australian-based Phase 2 RESCUE-ALS trial evaluated the safety, pharmacokinetics, pharmacodynamics, and effectiveness of nine months of treatment with CNM-Au8 (30 mg) against a placebo in 45 adults with early ALS — meaning that less than two years had elapsed since the first disease symptoms became evident, or less than one year since diagnosis.

Pharmacokinetics refers to a therapy’s movement into, through, and out of the body, while pharmacodynamics assesses how it affects the body.

Top-line results showed that CNM-Au8 failed to meet the study’s main goals of preventing motor neuron loss and lung function decline. However, additional trial analyses indicated that the experimental therapy significantly slowed disease progression and improved quality of life compared with a placebo, while also showing potential to improve long-term survival.

The long-term survival analysis concerned data from RESCUE-ALS’s participants who chose to enter its OLE study (20 of the CNM-Au8 group and 16 of the control group) and those who did not and whose health status was captured when possible. All patients in the OLE study are taking CNM-Au8 for up to 96 weeks, or about 22 months (totaling about 2.5 years).

Results, as of May 24, showed that patients originally assigned to CNM-Au8 had a 62% lower risk of death, compared with those initiating the therapy nine months later. However, these differences failed to reach statistical significance.

Newly announced data, with a data cut-off date of July 5, concerned available long-term survival findings from 43 RESCUE-ALS participants: 22 from the CNM-Au8 group and 21 from the placebo group.

There were five deaths in the CNM-Au8 group and 14 deaths among those originally assigned to a placebo.

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Since more than half of patients in the CNM-Au8 group were still alive at the latest assessment, median survival could not be measured. Patients on a placebo during RESCUE-ALS and who either left or switched to the therapy in the OLE lived for a median of 23.1 months (nearly two years).

Further analyses showed that patients starting CNM-Au8 in RESCUE-ALS had a significantly lower risk of death, by 70%, compared with those originally assigned to a placebo.

The therapy was generally well-tolerated, with no significant safety findings reported during the OLE study.