CNM-Au8 found to delay clinical worsening in ALS HEALEY trial
Results of new analyses 'highly encouraging,' developer Clene says
Treatment with CNM-Au8 significantly delayed clinical worsening in people with amyotrophic lateral sclerosis (ALS), according to new exploratory analyses from the therapy’s arm of the HEALEY ALS platform trial.
The experimental therapy, from Clene Nanomedicine, had previously been found to reduce the risk of death by more than 90% during the six-month trial.
Clene’s announcement of the new analyses comes on the heels of the latest data from the RESCUE-ALS Phase 2 trial (NCT04098406) and its open-label extension part (NCT05299658). These studies demonstrated that a longer time on CNM-Au8 was associated with significantly slower disease progression compared with a nine-month treatment delay.
The new findings are “highly encouraging,” Rob Etherington, Clene’s CEO, said in a company press release, adding, “When supported by a confirmatory trial, this would give people living with ALS longer periods of independence, which are precious to them and their families.”
Etherington noted that the company will discuss the findings with the U.S. Food and Drug Administration, with the goal of identifying a path toward regulatory approval. Meanwhile, plans for a Phase 3 trial of CNM-Au8, called RESTORE-ALS, are underway.
Therapy previously found to reduce risk of death more than 90%
CNM-Au8 is an oral liquid suspension of gold nanocrystals. It’s expected to support the energetic needs of nerve cells, protecting them against oxidative stress, a type of cellular damage implicated in ALS.
The novel HEALEY platform trial (NCT04297683) is the first clinical study designed to simultaneously test several ALS treatment candidates — an approach expected to cut costs and accelerate the development of new therapies.
Adults with ALS who’ve had symptom onset within the last three years are screened through the trial’s master protocol. If found eligible, they are randomly assigned to one of the trial’s arms that is accepting new participants. Recruitment is ongoing at dozens of sites in the U.S.
The CNM-Au8 trial arm (NCT04414345) enrolled 161 patients who were randomly assigned to receive oral CNM-Au8 (30 mg or 60 mg) or a placebo, given daily for 24 weeks or about six months. Because HEALEY uses a shared placebo group, it allows 75% of participants in each arm to be given each investigational treatment.
The trial did not meet its main goal of slowing functional declines, as assessed by changes in the ALS Functional Rating Scale Revised (ALSFRS-R) scores. Nor did it demonstrate benefit in a joint assessment of survival and disease progression or measures of lung function.
Still, exploratory analyses showed that CNM-Au8 at its 30 mg dose reduced the risk of death, and the combined risk of death and need for permanently assisted ventilation, by more than 90% after six months.
Now the new analyses show that 30 mg of CNM-Au8 also significantly reduced the risk of overall clinical worsening by 74%. This measure assesses the risk of death, breathing tube placement, need for assisted ventilation for more than 22 hours a day, or feeding tube placement.
Individually, the risk of each of these measures also decreased with the experimental treatment.
In particular, the risk of feeding tube placement and the risk of death or permanent ventilation assistance were both significantly reduced — by 74% and 98%, respectively. Other, non-significant risk reductions also were observed for death (95%), assisted ventilation (63%), ALS-related hospitalizations (84%), and all-cause hospitalizations (69%).
Analyses taking into account patients’ blood levels of neurofilament light chain, a biomarker of nerve cell damage, led to similar reductions, Clene noted.
Additionally, the treatment was found to be well tolerated, with no significant safety issues reported.
After completing the six-month trial, participants could join an open-label extension phase, in which all are receiving the 30 mg dose of CNM-Au8.
When supported by a confirmatory trial, this would give people living with ALS longer periods of independence, which are precious to them and their families.
Additional analyses from the HEALEY trial are planned, including an examination of disease progression biomarkers, as well as assessments of clinical worsening and survival in the extension phase. Overall, these findings will inform the design of future trials, according to Clene.
The benefits of the treatment identified thus far “could prove to be profoundly beneficial to people living with ALS and their families,” said Merit Cudkowicz, MD, the principal investigator of the HEALEY study. Cudkowicz also is the director of the Sean M. Healey & AMG Center for ALS, and chief of the department of neurology at Massachusetts General Hospital in Boston.
“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,” Cudkowicz said.
James Berry, MD, the co-lead investigator for the CNM-Au8 trial arm, said the new results “provide ample rationale to continue its development in a Phase 3 ALS trial.”
“We would like to thank the hundreds of people living with ALS and their loved ones and caregivers, who have dedicated themselves to participation in this trial, and we look forward to learning more about the impact of CNM-Au8 on ALS progression in the future,” Berry added.