Early CNM-Au8 Continues to Show Survival Benefits in ALS Patients
CNM-Au8 is designed to prevent nerve cell death, slow disease progression
Early treatment with CNM-Au8 continues to demonstrate survival benefits in people with amyotrophic lateral sclerosis (ALS) compared with those who started treatment nine months later, according to an update from its developer, Clene Nanomedicine.
The updated results come from the RESCUE-ALS Phase 2 trial (NCT04098406) and its open-label extension (OLE) study (NCT05299658), which are evaluating the investigational treatment in people with early ALS.
The findings were presented in a poster titled, “Evidence for A Survival Benefit with CNM-Au8 Treatment: Interim Results from the RESCUE-ALS Trial Long-Term Open Label Extension,” at the 2022 American Association of Neuromuscular and Electrodiagnostic Medicine Clinical and Scientific Conference, Sept. 21–24 in Tennessee.
“These clinical and survival data from RESCUE-ALS contribute to the growing body of evidence supporting the potential for CNM-Au8 as a disease-modifying therapy for amyotrophic lateral sclerosis (ALS),” Robert Glanzman, MD, Clene’s chief medical officer, said in a company press release.
CNM-Au8 is an oral liquid suspension containing gold nanocrystals. It’s designed to protect nerve cells by supporting their energy demands and safeguarding them against oxidative stress, a type of cellular damage implicated in ALS. Clene believes this mechanism of action can prevent nerve cell death and slow ALS progression.
The RESCUE-ALS trial enrolled 45 adults with early ALS, meaning less than two years had elapsed since the first symptoms appeared, or less than one year since a diagnosis was made. Participants were enrolled in Australia and randomized to receive oral CNM-Au8 (30 mg) or a placebo daily for 36 weeks (about nine months).
Top-line data from RESCUE-ALS showed the trial failed to reach its main and key secondary goals of preventing the loss of motor neurons and lung function decline in that time.
Potential survival benefit of CNM-Au8
But additional analyses showed CNM-Au8 significantly slowed disease progression and improved quality of life. It also slowed nerve cell loss in the patients with limb-onset ALS and showed potential for improving long-term survival.
After the trial, most participants opted in on the trial’s open-label extension wherein all are receiving CNM-Au8 for up to 96 weeks (nearly two years).
The long-term survival analysis presented in the poster reflected up to 137 weeks of follow-up data across RESCUE-ALS and the extension trial with a cutoff date of Aug. 31.
Consistent with findings from the July 5 cutoff date, the updated results showed patients who were assigned CNM-Au8 during RESCUE-ALS had a 70% lower risk of death compared with those who started treatment in the OLE part.
The treatment also showed significant survival benefits relative to the predicted median survival if patients were left untreated. This analysis was based on the European Network To Cure ALS (ENCALS) prediction model, which takes into account each person’s baseline characteristics to forecast survival. Here, and as previously reported, CNM-Au8 treatment decreased the mortality risk by about 64% compared with predicted survival.
“The impressive ALS survival benefits seen with CNM-Au8 treatment corroborate our thesis – energetic support of neurons may protect CNS [central nervous system] health and slow neurodegenerative disease progression,” Rob Etherington, Clene’s CEO, said.
CNM-Au8 also is being evaluated in the HEALEY platform trial (NCT04297683), which is testing several potential ALS therapies against a shared placebo group. In the CNM-Au8 arm (NCT04414345), about 160 ALS patients were randomly assigned to CNM-Au8 at 30 or 60 mg, or a placebo daily for six months.
Results from this arm are expected in the coming months. If they’re positive, Clene plans to use them to support regulatory applications for the therapy’s approval for ALS.
“We look forward to upcoming results from the HEALEY ALS Platform Trial and advancing CNM-Au8 development in ALS and other neurodegenerative diseases, including multiple sclerosis and Parkinson’s,” Etherington said.