Slower ALS progression seen with long-term CNM-Au8 use in trial
RESCUE-ALS update shows gains in patients treated for more than 2 years
Amyotrophic lateral sclerosis (ALS) patients treated earlier with CNM-Au8 in a clinical trial experienced a significantly slower disease progression than those who started treatment nine months later.
These latest findings from the RESCUE-ALS Phase 2 trial (NCT04098406) and its open-label extension (OLE) study (NCT05299658) add to earlier reports that people on this gold nanocrystal therapy for longer periods saw a significant survival benefit.
“The totality of data generated from the CNM-Au8 ALS clinical program and the long-term patient benefits are highly encouraging,” Steve Vucic, PhD, a trial co-investigator, said in a press release from CNM-Au8’s developer, Clene Nanomedicine.
“It is extraordinarily notable that a nine-month difference in treatment initiation … substantially preserved long-term function,” added Vucic, a professor holding the Northcott chair of neurology at the University of Sydney. “With its favorable tolerability profile and ability to be used alone or in combination with other ALS therapies, early treatment with CNM-Au8 may play an essential role in the treatment of ALS.”
Analyses of treatment vs. placebo groups well into open-label extension trial
CNM-Au8 is an oral liquid suspension containing gold nanocrystals designed to support nerve cells’ energetic needs and to protect them from oxidative stress, a type of cellular damage implicated in ALS. It aims to prevent nerve cell death and slow ALS disease progression.
The RESCUE-ALS trial enrolled 45 adults with early ALS, meaning symptoms first appearing over the previous two years, who were randomized to a liquid suspension containing 30 mg of CNM-Au8 or a placebo, once daily for 36 weeks or about nine months.
The trial failed to meet its main goal of preventing the loss of motor neurons, specialized cells that are progressively damaged in ALS, as well as a key secondary goal of slowing lung function decline.
However, additional analyses supported treatment slowing clinical worsening, with fewer patients on CNM-Au8 experiencing a six-point decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores compared with those given a placebo (60% vs. 80%).
CNM-Au8’s use also significantly improved quality of life and resulted in a 37% reduction in the risk of disease progression, defined as death, or the need for breathing support or feeding tube placement.
Thirty-six patients, 90%, chose to enter the trial’s open-label extension, in which all are receiving CNM-Au8 once daily.
Previous analyses indicated that patients initially assigned to CNM-Au8 in the main RESCUE-ALS trial had a 70% lower risk of death than those starting treatment nine months later in the OLE.
Newly released findings cover patients treated for up to 120 weeks (about 2.3 years) across the main trial and its OLE, with a data cut-off date of July 14. These findings also were shared in a recent investor presentation.
In line with main trial analyses, CNM-Au8 significantly slowed ALSFRS-R score declines, indicating preserved function, among patients on long-term treatment compared with those initially given a placebo.
The slower decline was observed during first 48 weeks of OLE treatment, a somewhat expected finding as placebo group patients would not yet have achieved effective bloodstream concentrations of the therapy.
Good safety with experimental ALS treatment reported
What’s notable is slower ALSFRS-R declines in patients on continuous CNM-Au8 use, relative to later starters, across weeks 60 to 120, when all OLE patients had effective blood concentrations of CNM-Au8, according to Clene.
Patients starting the therapy nine months later, on average, declined by six ALSFRS-R points more than those given CNM-Au8 from the main trial’s start.
Consistently treated patients also showed significant delays in the time to clinical worsening, including death, or a need for ventilation support or a feeding tube. Their risk for any of these events was more than 50% lower than the later treatment group.
CNM-Au8 was well tolerated with no long-term safety concerns, the company noted.
RESCUE-ALS survival data also were consistent with top-line data from the CNM-Au8 arm (NCT04414345) of the HEALEY platform trial (NCT04297683), which found that a 30 mg dose lowered the risk of death by about 90% after some six months of treatment.
This trial also failed to met its primary goal of slowing disease progression, as measured in ALSFRS-R score changes.
“The open-label data at 48 weeks and through 120 weeks from randomization suggests that CNM-Au8 has the ability to meaningfully improve patient daily functional status over longer periods of time, together with sustained treatment effects on ALS disease progression and survival,” said Matthew Kiernan, PhD, a RESCUE-ALS trial investigator and University of Sydney professor holding the Bushell chair of neurology.
Recent analyses also confirm the therapy’s “excellent safety profile,” Kiernan added.
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