CNM-Au8 Demonstrates Significant Survival Benefit in HEALEY-ALS Interim Analysis

Merit Cudkowicz, MD

Newly announced 6-month findings from the HEALEY-ALS Platform trial, the first of its kind for amyotrophic lateral sclerosis (ALS), showed that treatment with CNM-Au8 (Clene Nanomedicine) was tolerable, with several meaningful delays in clinical worsening and increased survival benefit.¹

CNM-Au8 is an oral suspension of gold nanocrystals developed to restore neuronal health and function by increasing energy production and utilization. Over a 24-week treatment period, patients with ALS treated with 30 mg of CNM-Au8 demonstrated a 74% decreased risk on the composite endpoint of time to ALS clinical worsening (P = .035). This included the first instance of death, tracheostomy, initiation of permanent assisted ventilation for at least 22 hours per day, or placement of a feeding tube.

"These meaningful delays in clinical worsening, coupled with the previously suggested benefit in ALS patient survival and favorable tolerability profile of CNM-Au8 could prove to be profoundly beneficial to people living with ALS and their families," Merit Cudkowicz, MD, chief, Neurology Department, director, Sean M. Healey & AMG Center for ALS, and principal investigator of the HEALEY-ALS Platform trial, said in a statement.¹ "We hope to see these results persist and strengthen over an even longer-term follow-up period for patients who have entered the open-label portion of the trial, and for those individuals who will participate in Clene’s next ALS clinical trial."

In the CNM-Au8 treatment regimen, 161 participants were randomly assigned 3:1, with 120 planned for randomization across 2 active arms (30 mg and 60 mg) and at least 40 planned in placebo. Participants included were at least 18 years old, had a diagnosis of sporadic or familial ALS, and had less than 36 months since onset of weakness prior to screening.

Concurrent with a lower hazard of ALS clinical worsening, those in the 30 mg CNM-Au8 group had a 98% decreased risk of death or permanently assisted ventilation (P = .028) and 95% decreased risk of death (P = .053). In addition, this treated group demonstrated a 74% decreased risk of feeding tube placement (P = .035), 63% decreased risk of assisted ventilation (P = .058), 84% decreased risk of ALS-related hospitalization (P = .107), and 69% decreased risk of all-cause hospitalization (P = .065).

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"In addition to these highly encouraging delayed time to clinical worsening results, we will be analyzing disease progression based on validated biomarkers from both the double-blind and open label periods of the HEALEY ALS Platform Trial," Robert Glanzman, MD, FAAN, chief medical officer, Clene Nanomedicine, said in a statement.¹ "We also plan to perform similar analyses of clinical worsening and survival beyond the 6-month double-blind period. These data will inform the design of the planned phase 3 trial with CNM-Au8, RESTORE-ALS. We sincerely thank the people living with ALS, as well as their families, for their willingness to engage in clinical research and participate in the HEALEY ALS Platform Trial."

In early October 2022, topline findings from the CNM-Au8 arm of HEALEY-ALS were announced, with data showing that the agent did not meet its primary and secondary end points. Over the 24-week period, treatment with the therapy results in 2% (95% CI, –20 to 19) slowing of disease progression, demonstrated by scores on ALS Functional Rating Scale-Revised (ALSFRS-R) adjusted for mortality. Although survival benefit was observed in the 30-mg dose group, this was not the case for the 60-mg group, the larger of the 2 doses assessed.²

Across both CNM-Au8 groups, secondary end points showed no statistically significant change over the 24-week treatment period. There were no drug-related serious adverse events or significant safety signals found in either group. The statistically significant results were statistically consistent for the 30-mg dose group between the regimen only and full analysis sets, which included shared placebo from other regimens participating in the platform trial.

REFERENCES
1. CNM-Au8 associated with delayed time to key clinical progression events at six months supporting a survival benefit in the Healey ALS Platform trial. News release. March 9, 2023. Accessed March 9, 2023. https://www.globenewswire.com/news-release/2023/03/09/2623829/0/en/CNM-Au8-Associated-With-Delayed-Time-to-Key-Clinical-Progression-Events-at-Six-Months-Supporting-a-Survival-Benefit-in-the-Healey-ALS-Platform-Trial.html
2. Clene reports topline results demonstrating survival signal for CNM-Au8 in Healey ALS Platform trial. News release. Clene Nanomedicine. October 3, 2022. Accessed March 9, 2022. https://www.globenewswire.com/news-release/2022/10/03/2526765/0/en/Clene-Reports-Topline-Results-Demonstrating-Survival-Signal-for-CNM-Au8-in-Healey-ALS-Platform-Trial.html