CNM-Au8 extends patient survival in 2 ALS compassionate use studies
Data support plans for Phase 3 trial of oral therapy, expected to start soon
Treatment with CNM-Au8 was shown to significantly prolong survival — relative to the natural history of the disease — among people with advanced amyotrophic lateral sclerosis (ALS) who took part in two expanded access programs (EAP), also known as compassionate use programs.
The findings from these EAPs, which allow an experimental therapy’s use in patients outside of clinical trials, are consistent with previous observations in Phase 2 studies that tested the oral therapy in less severely affected individuals with ALS.
“These EAP results help us better understand how people living with more advanced disease respond to treatment,” Richard S. Bedlack Jr., MD, PhD, a professor at the Duke University School of Medicine, in North Carolina, and a member of the steering committee for one of the EAP studies, said in a press release announcing the results.
The data support developer Clene Nanomedicine’s plans to advance CNM-Au8 to Phase 3 clinical testing, which the company has previously noted is expected to begin this year.
Clene last October also was awarded a four-year, $45.1 million grant from the National Institutes of Health to support the launch of a third EAP. That compassionate use program will particularly seek to reach U.S. patients in rural and remote areas virtually via a telemedicine platform. It’s expected to start enrolling in all 50 states during the first half of this year.
“Collecting data of peoples’ experience beyond clinical trials is extremely important in rare diseases like ALS,” Bedlack said, adding that the EAP data “warrant consideration to be included in Clene’s discussions about CNM-Au8 with regulatory agencies.”
Compassionate use programs allow patients to get treatment outside trials
CNM-Au8 is an oral liquid suspension of gold nanoparticles. It aims to slow ALS progression by supporting nerve cells’ energy needs and protecting against types of cellular damage that are implicated in the neurodegenerative disease.
Phase 2 clinical trials of the therapy candidate are wrapping up, among them the RESCUE-ALS study (NCT04098406) and its open-label extension (NCT05299658), as well as an arm of the HEALEY ALS platform trial (NCT04297683). RESCUE-ALS tested CNM-Au8 against a placebo in 45 patients, while its extension involved an estimated 40 individuals. In that open-label part, both researchers and participants know the exact medication that’s being given. The HEALEY ALS trial, meanwhile, is a multicenter, multi-regimen clinical trial evaluating several treatment candidates at the same time.
For their part, EAPs are regulated pathways that intend to offer access to an investigational therapy outside of clinical trial settings for patients with serious or life-threatening diseases for whom no satisfactory treatment is available.
The CNM-Au8 EAPs, both of which are still active, include patients in the U.S. who were not eligible for CNM-Au8 clinical trials — usually because their disease was too advanced.
The first EAP (NCT04081714) was launched in 2019 at the Sean M. Healey & AMG Center for ALS at Massachusetts General Hospital, where the HEALEY ALS platform trial is also being led. A second EAP (NCT05281484) was launched in 2021, and is available to patients at 16 U.S. sites associated with the Northeast ALS Consortium.
In addition to expanding patient access to the therapy, the EAPs are expected to provide additional safety and efficacy data for regulators to review when deciding on the treatment’s possible approval.
Comparing use of CNM-Au8 to natural history, or no treatment
Clene’s recent update concerned pooled data from the EAPs, through which more than 250 patients have been treated with CNM-Au8 at a daily oral dose of 30 mg.
Survival analyses were conducted to compare outcomes from a total of 220 EAP participants — who had been treated for up to four years — with data from matched untreated ALS patients in either of two databases.
The first was PRO-ACT, a large database containing information from more than 12,000 ALS patients who participated in previous clinical trials. The other was the ALS/MND Natural History Consortium, a study that has collected real-world data from about 1,700 ALS patients.
The results indicated that CNM-Au8 was associated with a significant, 68% decreased risk of death compared with people in PRO-ACT, and a significant, 57% lower risk relative to the ALS/MND Consortium, according to the company.
The long-term safety and survival data from the CNM-Au8 expanded access programs add to the available data supporting CNM-Au8 moving rapidly to Phase 3 testing in ALS. … This is one of a few therapies with positive Phase 2 data that must go forward to Phase 3 trials.
CNM-Au8 was well tolerated, with no serious adverse events deemed related to treatment. Also, no significant safety findings were identified.
Overall, the findings are consistent with previous analyses from the RESCUE and HEALEY-ALS trials, in which treatment with CNM-Au8 prolonged survival and delayed clinical worsening in ALS patients.
“The long-term safety and survival data from the CNM-Au8 expanded access programs add to the available data supporting CNM-Au8 moving rapidly to Phase 3 testing in ALS,” said Merit Cudkowicz, MD, chair of neurology and director of the Healey & AMG Center at Mass General Hospital, a principal investigator of the EAP being conducted at Healey & AMG Center, and a professor at Harvard Medical School.
“This is one of a few therapies with positive Phase 2 data that must go forward to Phase 3 trials,” Cudkowicz added.
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