AAN 2024: Sustained myelin, nerve cell gains with long-term CNM-Au8
Findings buttress Clene Nanomedicine's plans to launch Phase 3 trial in MS
Long-term treatment with Clene Nanomedicine‘s experimental oral therapy CNM-Au8 led to signs of sustained improvements in nerve and myelin health for people with relapsing-remitting multiple sclerosis (RRMS) over three years, according to new data from the VISIONARY-MS clinical trial.
The findings continue to support Clene’s plans to launch a Phase 3 trial of CNM-Au8 in MS, which may support applications toward the drug’s approval.
“As an MS neurologist, for me these results are particularly exciting and provide a clear impetus for a Phase 3 study,” Michael Barnett, PhD, a clinical advisor for the trial, said during a talk at the American Academy of Neurology (AAN) 2024 Annual Meeting, held April 13-18, in Denver and online. Barnett’s presentation was titled, “VISIONARY-MS Long-Term Extension: A Multi-Centre, Open-Label Long-Term Extension Study of CNM-Au8 in Patients with Stable Relapsing Multiple Sclerosis.”
Nerve cells require high levels of energy for the intensive work of sending electrical signals and problems with energy production may contribute to the progression of many neurological disorders, including MS.
CNM-Au8 contains a liquid suspension of gold nanoparticles that are designed to boost nerve cells’ energy production. This mechanism is distinct from approved disease-modifying therapies (DMTs) for MS, which work to reduce inflammation in the brain.
“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 Barnett, who serves as a professor of neurology at the University of Sydney, in a Clene press release.
Long-term gains with CNM-Au8
The Phase 2 VISIONARY-MS clinical trial (NCT03536559) tested CNM-Au8 against a placebo in 73 people with RRMS who hadn’t had a relapse for at least six months before entering the study. All the participants had chronic optic neuritis, or inflammation of the optic nerves that connect the eyes to the brain, which causes vision problems, and were randomly assigned to one of two doses of CNM-Au8 (15 mg or 30 mg) or a placebo, daily for nearly a year. Most also took background DMTs during the trial.
After a year, those given CNM-Au8 had significant improvements in vision, with data suggesting the therapy improved the health of nerve fibers in the brain.
After the placebo-controlled study, 55 participants entered into an extension study dubbed VISIONMS-LTE (NCT04626921). There, all were treated with CNM-Au8 at 30 mg per day for two years — for a total of three years of treatment for those given the therapy in the original trial.
No serious side effects related to the therapy have been documented, said Barnett, who noted the therapy has been “extremely well tolerated.”
Earlier this year, Clene announced data that showed improvements in vision with CNM-Au8 were maintained for three years for those who started on the drug in the placebo-controlled part. Improvements on cognitive assessments also were maintained after three years on CNM-Au8 and those who switched from a placebo to CNM-Au8 in the extension study saw improvements in these measures.
Repair of damaged optic nerves
Barnett’s presentation at AAN included new data that showed the therapy also led to sustained improvements in the amplitude and latency of patients’ visual evoked potentials.
When a person sees something, an electrical signal is sent along the optic nerves from the eyes to the parts of the brain that make sense of what’s being viewed. Visual evoked potential latency and amplitude are measures of how fast and strong this electrical signal is, and are reduced when the optic nerves are damaged. The improvements in visual evoked potential in these patients, all of whom had optic neuritis at the trial’s start, suggest the damaged optic nerves are repairing.
MRI trial data also indicated CNM-Au8 led to long-term increases in markers of myelin repair, or remyelination. Myelin is a fatty substance that wraps around nerve fibers to help them send electrical signals, but is damaged by the misguided inflammatory attacks in MS.
The data collectively show “not only paraclinical evidence of remyelination and improved axonal [nerve fiber] function, but measurable improvements in previously fixed clinical deficits,” Barnett said.
“This is a very exciting data set that gives hope to the millions of people who are suffering from this disabling disease,” said Benjamin Greenberg, MD, head of medicine at Clene. “Observing such a profound clinical benefit with corresponding improvements in physiologic measures utilizing a mechanism that does not target immune system modulation has never been demonstrated in prior multiple sclerosis trials.”
Note: The Multiple Sclerosis News Today team is providing coverage of the American Academy of Neurology (AAN) 2024 Annual Meeting April 13-18. Go here to see the latest stories from the conference.
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