Clene Nanomedicine’s CNM-Au8 demonstrated surprising improvements in some MS patients, despite the study being halted early due to COVID-19.
Clene CEO Rob Etherington, Courtesy of Clene Nanomedicine
Clene Nanomedicine’s additive therapeutic CNM-Au8 demonstrated “surprising” improvements in some multiple sclerosis (MS) patients, despite the Phase II trial being halted early due to COVID-19.
On Monday, the Utah-based company announced that its investigational gold bioenergetic nanocatalyst CNM-Au8 provided consistent clinical improvements across multiple paraclinical biomarkers in trial participants with stable relapsing-remitting multiple sclerosis (RRMS) who have a history of chronic visual impairment. CNM-Au8 is designed to catalyze biocelluar reactions in order to spur the repair and reversal of neuronal damage.
The Phase II proof-of-concept VISIONARY-MS study was assessing CNM-Au8 as an add-on therapy for stable RRMS participants with chronic optic neuropathy. The primary endpoint, which was met, was the change in best corrected-low contrast letter acuity (BC-LCLA) from baseline to week 48 in the clinically affected eye.
Rob Etherington, Clene CEO, told BioSpace that he was “pleasantly surprised” by these improvements. He said the data provide “independently assessed quantitative physiological evidence” that supports the idea that CNM-Au8 offers both neuroprotective and remyelinating effects to these patients.
Hold, Please: COVID-19 Brings VISIONARY-MS to a Halt
One of the concerns with MS is that even though patients may be stable on their current treatment, there can still be a decline in neurological function. Clene hopes that CNM-Au8 can halt or even reverse that. The improvements seen in the VISIONARY-MS trial support the advancement of CNM-Au8 into Phase III clinical development, a study that hopefully won’t be marred by the COVID-19 pandemic, Etherington said.
The VISIONARY-MS trial was stopped due to the pandemic, and it only included 73 of the 150 expected patients. Despite the early termination of the study, Clene executives met with trial officials before unblinding the data and changed the pre-specified p-value to p-0.10. The analysis was then conducted in a modified intent-to-treat (mITT) population, which the company noted “censored invalid data.”
Additionally, Clene excluded data from a single site with LCLA testing execution errors. Other changes in the study included the exclusion of the timed 25-foot walk data from one subject with a change in mobility assist device. Even with these changes, the intent-to-treat (ITT) results were not significant, Clene noted, despite the fact that they were “directionally consistent” with the mITT results.
In its announcement, the company said that there were consistent improvements favoring the benefit of CNM-Au8 seen across multiple paraclinical biomarkers, including multifocal visual evoked potentials (mfVEP) amplitude and latency, optical coherence tomography (OCT) and MRI endpoints, including magnetization transfer ratio and diffusion tensor imaging metrics. In contrast, the patients who did not receive CNM-Au8 saw their biomarker conditions worsen during the same 48-week period.
During the company’s call with investors on Monday, Benjamin Greenberg, a professor of neurology and one of the trial’s clinical advisers, noted that the trial was designed to evaluate whether treatment of neuronal and glial energetic failure can support remyelination and neuroprotection in people living with multiple sclerosis.
“These results further demonstrate the potential of CNM-Au8 to drive neuronal cellular energy production in patients struggling with MS and other neurodegenerative diseases,” Etherington said. “Although it was halted early due to the pandemic, the unblinded data generated results that provide support for the advancement of CNM-Au8 into Phase III studies.”
Looking to Phase III
What the Phase III study will look like has yet to be determined. Etherington said the company will spend the next several months mining the data from the VISIONARY-MS study, particularly in some of the subpopulations of participants.
“Will be spending the rest of the fall to understand the biomarker data and confirming with the FDA about the design of the (Phase III) study,” Etherington said.
He added that Clene is open to partnering with other pharma companies in the multiple sclerosis space on the future development of CNM-Au8 for this indication.
CNM-Au8 in ALS
The data from the MS study comes weeks after Clene released interim data from its clinical study of CNM-Au8 in amyotrophic lateral sclerosis. Interim data from the Phase II RESCUE-ALS study showed that ALS patients who received CNM-Au8 during the study saw a significant survival benefit compared to patients who were given a placebo. Only five patients who were on the CNM-Au8 arm died, compared to 14 patients on placebo. Updated data from this study is expected later this year, Etherington said.
Also in ALS, the company is awaiting topline data from another study, the HEALEY ALS platform trial, which is expected later this quarter.
Looking at the benefits CNM-Au8 has posted in the two very different diseases, Etherington expressed excitement that “the same asset at the same dose” has potential applications across both diseases.
