CNM-Au8 seen to extend survival by more than 1.5 years in ALS trial
70% lower death risk over 2 years found for patients on oral therapy
Treatment with CNM-Au8 was found to significantly delay disease progression and prolong survival, by more than 1.5 years, among adults with early-stage amyotrophic lateral sclerosis (ALS) in the RESCUE-ALS trial and its open-label extension phase.
That’s according to two different statistical analyses, which overall showed that patients who received CNM-Au8 had a 70% lower risk of death over two years of follow-up compared with those never given the medication.
Indeed, the new analyses revealed a “19.3 month significant survival difference for CNM-Au8 treated participants versus [those on a] placebo,” Clene Nanomedicine, the company developing CNM-Au8, stated in a press release.
“The data that continues to be received from the RESCUE-ALS open label extension study is truly impressive, and now shows consistently significant decreased risk of death greater than 70% using two different long-term analysis models,” said Matthew Kiernan, PhD, of the University of Sydney, one of the trial’s clinical advisors.
“The survival benefit across treatment arms is linked to less worsening of disease, as experienced by ALS patients. At the same time, the further safety data confirms that CNM-Au8 is well tolerated in ALS patients,” Kiernan added.
Main trial of CNM-Au8 failed to meet primary, secondary goals
The oral therapy is a suspension of gold nanoparticles that’s intended to slow ALS progression by preventing the death of the motor nerve cells that are progressively lost in the disease.
CNM-Au8 is believed to promote nerve cell survival by boosting energy production and protecting against a type of cellular damage, called oxidative stress, that’s implicated in ALS .
The Phase 2 RESCUE-ALS trial (NCT04098406), sponsored by Clene and launched in late 2019, enrolled 45 adults with early ALS at two sites in Australia. All had developed their first symptoms of the progressive disorder in the prior two years.
The participants were randomly assigned to receive CNM-Au8, at a dose of 30 mg, or a placebo, given as a liquid suspension once daily for 36 weeks, or about eight months. The therapy was given in addition to standard ALS medications.
Following the main trial, most participants (90%) entered into an open-label extension (NCT05299658), in which all would be given CNM-Au8 for up to 120 weeks, or more than two years.
The main trial had failed to meet its primary and key secondary goals of improving motor nerve cell health and slowing lung function declines after 36 weeks.
However, additional analyses spanning the trial and its extension have indicated a survival benefit and slower disease progression among patients who started the therapy eight months earlier relative to those who switched from the placebo in the extension phase.
Survival benefits with CNM-Au8 still being seen in extension trial
Now, Clene has reported that the survival benefits of CNM-Au8 are still being observed as of July 2023 — after two years in the extension trial.
Specifically, patients who started CNM-Au8 eight months earlier had a median survival of 34.2 months, or almost three years, compared with 24.1 months, or about two years, among those who switched from placebo. That’s a survival benefit of 10.1 months, and it amounts to a 46% lower risk of death among those originally assigned to CNM-Au8.
Investigators also conducted another survival analysis wherein the data were adjusted to subtract the potential survival benefits received by those who started on a placebo and then switched to CNM-Au8.
Essentially, the analysis estimated survival in this group if the patients had remained on a placebo and never switched over. That survival was determined to be 14.9 months, or about 1.2 years.
Here, the survival benefits of those always on CNM-Au8 were even more pronounced, with patients living about 19.3 months longer relative to those on a placebo. This was associated with a 75% lower risk of death in participants on continuous CNM-Au8.
A median survival improvement of 19.3 months provides people living with ALS, their families, and caregivers more time that is so invaluable, and adds to the totality of data we are seeing in our ALS clinical program.
The researchers then compared the survival of individuals treated with CNM-Au8 with historical placebo-treated patients — controls whose data were contained in the PRO-ACT ALS patient database. In that analysis, treatment with CNM-Aug was associated with a 70% lower risk of death.
Patients initially assigned the experimental therapy in the main trial also were found to be at a 52% lower risk of clinical worsening compared with those who started treatment eight months later. Clinical worsening was defined as the occurrence of one of several outcomes: death, breathing tube placement, assisted ventilation, or feeding tube placement.
Among open-label participants treated with CNM-Au8, 42% are still alive up to 3.5 years after their enrollment in RESCUE-ALS — and up to 6.6 years after their ALS symptom onset — according to Benjamin Greenberg, MD, head of medical at Clene.
Greenberg called this finding “a profoundly meaningful milestone for people living with this devastating disease.”
“A median survival improvement of 19.3 months provides people living with ALS, their families, and caregivers more time that is so invaluable, and adds to the totality of data we are seeing in our ALS clinical program,” Greenberg said.
CNM-Au8 also shows benefit in ALS platform trial
Similar findings also were observed in the CNM-Au8 arm of HEALEY ALS (NCT04297683), a platform trial that is investigating multiple ALS therapies simultaneously as a way to reduce costs and accelerate treatment development.
In that platform trial arm, treatment with 30 mg CNM-Au8 for six months lowered the risk of death by more than 90%. Moreover, significant reductions also were observed in the risk of needing a feeding tube, assisted ventilatory support, or being hospitalized.
Additionally, in more than 475 collective years of CNM-Au8 exposure in patients with several neurodegenerative disorders — ALS, multiple sclerosis, and Parkinson’s disease — no safety signals have been identified, according to researchers. Most reported side effects have been mild to moderate in severity, and temporary.
Side effects reported in RESCUE-ALS include nausea, bruising, abdominal discomfort, and aspiration pneumonia, or inflammation caused by food or liquids inhaled into the airways.
Clene has reported plans to launch a Phase 3 trial of CNM-Au8 called RESTORE-ALS. Should results be positive, the data may support regulatory applications for the therapy’s approval.
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