Prof. Michael Barnett
An investigational neuroprotective drug can produce sustained improvements in neurological functions suggestive of repair and remyelinating effects in MS patients, according to Australian researchers.
At the American Academy of Neurology (AAN) 2024 meeting recently Professor Michael Barnett from the University of Sydney presented results from a phase 2 study of a product known as CNM-Au8 which was used adjunctively to disease modifying therapies in 55 patients with stable relapsing MS and chronic optic neuropathy.
The therapy is an oral treatment that is described as a ‘cellular energetic nanocatalyst’ that provides mitochondrial support and increased energetic capacity in neurons and glia.
Prof. Barnett presented the three year results (link here) from an extension of the VISIONARY-MS randomised controlled trial that originally involved 69 patients randomised to either CNM-Au8 or placebo.
Results from the initial 48-week double-blind period showed that CNM-Au8 treatment improved low contrast letter acuity and global neurological function compared to placebo.
In a 96-week long term extension (LTE) period of the study, 55 of the participants were assessed for further changes in clinical outcomes.
According to Prof. Barnett, at three years follow up, the improvements in on low contrast letter acuity and on the modified MS Functional Rating Scale seen during the double-blind period were maintained in patients treated with CNM-Au8 compared to placebo.
More than half of participants improved by 10 or more letters on a low-contrast Sloan eye chart, with increases of up to 38 letters (mixed model repeat measures, or MMRM vs. original baseline, p < 0.001).
Participants originally randomized to placebo who transitioned to CNM-Au8 after the 48-week double blind period into the open label extension also experienced significant improvement in vision as measured by low contrast letter acuity following treatment with 30 mg CNM-Au8 (MMRM vs. original baseline, p < 0.05).
Study participants treated with CNM-Au8 experienced up to 29 points of significant improvement (max score =110) in cognition and working memory as measured by the Symbol Digit Modality Test (SDMT) (MMRM vs. original baseline, p < 0.001).
Prof. Barnett said there was also physiologic functional evidence of repair and remyelination in patients treated with CNM-Au8. Patients showed significant improvements in both amplitude (MMRM vs. original baseline, p < 0.01) and latency (MMRM vs. original baseline, p = 0.06) as measured by multi-focal visual evoked potentials, physiologic measures of signal strength and speed along the visual pathway, markers of neuronal health and remyelination, respectively.
Structural evidence of repair and remyelination came from MRI measures of axial diffusivity, showing significant improvements in T2 brain lesions in study participants treated with CNM-Au8 (MMRM vs. original baseline, p < 0.05).
There were also improvements in MRI measures of T2 lesion myelin water fraction (MWF) and magnetization transfer ratio (MTR), markers of remyelination.
CNM-Au8 was well-tolerated, and no significant safety findings were observed.
The data collectively show “not only paraclinical evidence of remyelination and improved axonal function, but measurable improvements in previously fixed clinical deficits,” Prof. Barnett said.
“As an MS neurologist, for me these results are particularly exciting and provide a clear impetus for a Phase 3 study,” he told the AAN meeting in Denver, Colorado.
“The development of adjunctive therapies that not only prevent neurodegeneration, but also improve neuronal function with measurable clinical benefit, will fill a major unmet need for people living with MS,” said Prof. Barnett, a consultant neurologist at Royal Prince Alfred Hospital Sydney, a senior academic at the University of Sydney, Director of the RPAH MS Clinic and the MS Clinical Trials Unit at the Brain and Mind Centre.
The study was sponsored by Clene Nanomedicine Inc.