CNM-Au8 Shows Survival Benefit in HEALEY Trial: New Top-line Results
But Clene therapy fails to meet trial goals or slow decline in function
Treatment with a 30 mg dose of CNM-Au8 significantly reduced the risk of death, and the risk of death and permanent assisted ventilation, by more than 90% among people with amyotrophic lateral sclerosis (ALS), according to new top-line data from the CNM-Au8 arm of the HEALEY ALS platform trial.
Yet, Clene Nanomedicine‘s investigational treatment did not significantly slow functional and respiratory declines, failing to meet the trial’s primary and key secondary endpoints.
These findings are largely consistent with the results from the RESCUE-ALS Phase 2 trial (NCT04098406) and its ongoing open-label extension study (NCT05299658). Those studies similarly failed to meet these main goals but lowered the risk of death by about 70% in patients with early ALS.
“We are very pleased to see a survival benefit in a broad population of people who had already been living with ALS for up to three years,” Robert Glanzman, MD, Clene’s chief medical officer, said in a company press release, adding, “This is the second Phase 2 study demonstrating a survival benefit following CNM-Au8 treatment.”
Potential early access program for CNM-Au8
Discussions about a potential early access program of CNM-Au8 for eligible patients are now underway between Clene and the Sean M. Healey & AMG Center for ALS at the Massachusetts General Hospital (MGH), in Boston. That center is leading the HEALEY trial under the direction of Merit Cudkowicz, MD.
“These Healey ALS platform trial results support advancement of the CNM-Au8 30 mg dose. We look forward to discussions with U.S. regulatory authorities at an end of Phase 2 meeting for our CNM-Au8 development program in ALS,” Glanzman said.
The ongoing HEALEY platform trial (NCT04297683), which is still recruiting participants, is designed to simultaneously evaluate the effects of several ALS therapies against a shared placebo group — an approach designed to accelerate treatment development while reducing costs.
Potential participants, ages 18 or older, with a confirmed ALS diagnosis and symptom onset within the last three years, are first screened via the HEALEY master protocol, then randomized into one of the trial arms that’s enrolling patients. To date, there are 65 study locations across the U.S.
CNM-Au8 — an oral liquid suspension of gold nanocrystals — comprises one of the study arms; it is not recruiting.
The treatment is designed to support the energetic needs of nerve cells and other cells of the nervous system (glia) and to protect them from oxidative stress, a type of cellular damage implicated in ALS.
In the CNM-Au8 trial arm (NCT04414345), a total of 161 patients were randomly assigned to receive either a 30 mg or 60 mg dose of CNM-Au8 or a placebo, given daily for 24 weeks, or about six months. About 75% of the participants were given one of the CNM-Au8 doses, while the remaining patients received the placebo.
The primary goal was to assess whether CNM-Au8 could slow functional decline, as measured by changes in the ALS Functional Rating Scale Revised (ALSFRS-R) scores, among patients.
The trial failed to meet that goal, and also failed to show a significant benefit in the Combined Assessment of Function and Survival, a joint assessment of survival and disease progression. Lung function decline, as measured with slow vital capacity (SVC), also was not significantly slowed with either dose.
According to Glanzman, “CNM-Au8’s mechanism of enabling energy metabolism and efficiency may not be reflected in the slope of ALSFRS-R change after only 24 weeks of treatment.”
Still, additional exploratory analyses revealed that the 30 mg dose of CNM-Au8 led to a more than 90% reduction in both the risk of death and the combined risk of death and need for permanently assisted ventilation after 24 weeks. The survival benefits were similar when the CNM-Au8 was compared with the placebo group in the trial arm, as well as with the larger shared placebo group across the HEALEY trial.
Notably, the results became statistically significant when the analyses were adjusted for the patients’ risk scores at the study’s start. The 60 mg dose, however, did not demonstrate a survival benefit.
CNM-Au8 was well-tolerated, with no serious treatment-related adverse events or significant safety findings reported.
Full trial analyses, including data on disease biomarkers and other exploratory efficacy findings, are expected later this year. Meanwhile, participants will continue to be followed in an open-label extension study, in which all are receiving the 30 mg dose of CNM-Au8, according to Clene.
Coming up on the HEALY platform
“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,” said Cudkowicz, the principal investigator and sponsor of the HEALEY ALS platform trial, in an MGH press release.
Cudkowicz also is the director of the Sean M. Healey & AMG Center for ALS, chief of the department of neurology at MGH, and the Julieanne Dorn professor of neurology at Harvard Medical School.
“The survival results from this trial together with the consistent benefit seen in the open-label extension of the Phase 2 RESCUE-ALS trial, based on up to 31.5 months of long-term follow-up, support the rationale for treating neuronal and glial energetic failure with CNM-Au8,” said Rob Etherington, Clene’s president and CEO, in the company’s release, adding, “We believe supporting brain energetic capacity translates to patient benefit, including survival.”
Etherington said Clene is “pursuing paths, including strategic partnerships, and is in dialogue with various potential partners” in its continued development of CNM-Au8.
“Clene remains committed to advancing CNM-Au8 clinical programs to the ultimate goal of [U.S. Food and Drug Administration] approval,” Etherington said.
Other treatments being investigated in the HEALEY trial include Biohaven Pharmaceuticals’ verdiperstat (NCT04436510), Prilenia Therapeutic’s pridopidine (NCT04615923), and Seelos Therapeutics’ SLS-005 (NCT05136885). All of the trials are being conducted under the direction of Cudkowicz.
ABBV-CLS-7262, an investigational treatment from Calico Life Sciences and Abbvie, is likely next up for the platform trial.
“We thank the ALS community for its support of the Healey ALS platform trial,” said Michael Hotchin, Clene’s chief development officer. “Furthermore, we thank the site investigators for their research excellence and dedication to patients, and we thank Dr. Cudkowicz and the team at the Healey & AMG ALS center for their leadership and for the development of the platform trial.”
“Most importantly, we thank people living with ALS who participated in the study and their families for their effort and willingness to engage in clinical research,” added Hotchin.