CNM-Au8 leads to clinical gains for RRMS patients in extension study

Daily treatment with CNM-Au8 led to sustained improvements in vision and cognition for people with relapsing-remitting multiple sclerosis (RRMS), according to nearly three years of follow-up in the VISIONARY-MS trial and its open-label extension (OLE).

Developer Clene Nanomedicine plans to present full trial results at the upcoming ACTRIMS Forum in late February, while also looking for pharmaceutical partners to continue developing CNM-Au8 for MS.

The company previously indicated plans for a Phase 3 trial involving patients in whom disease progression is occurring in the absence of relapses, sometimes called “silent progression.”

“Clinically significant improvement is rarely seen in MS patients and this trial provides evidence of CNM-Au8’s potential to improve function in this population,” Benjamin Greenberg, MD, head of medicine at Clene, said in a company press release.

“These data continue to build a strong case in favor of pursuing CNM-Au8 in upcoming Phase 3 studies,” Greenberg added.

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CNM-Au8 thought to lead to nerve cells being more resilient to stressors

CNM-Au8 is a liquid suspension of gold nanoparticles that’s designed to increase energy production in the brain and spinal cord. This is thought to help nerve cells be more resilient against stressors that drive their damage and death in neurodegenerative conditions such as MS, amyotrophic lateral sclerosis, and Parkinson’s disease.

The Phase 2 VISIONARY-MS trial (NCT03536559) was designed to evaluate CNM-Au8’s ability to preserve or improve neurological function in people with stable RRMS, meaning they had not had a relapse or new MRI activity in at least six months. All had chronic optic neuropathy, or damage to the bundle of nerve fibers that sends signals between the eyes and the brain, which results in vision problems.

A total of 73 participants were enrolled and randomly assigned to receive oral CNM-Au8 (15 mg or 30 mg) or a placebo once daily for 48 weeks, or nearly a year. Nearly all of them (92%) were also being treated with background disease-modifying therapies.

The trial’s main goal was to evaluate for improvements in low contrast letter acuity (LCLA), an aspect of vision which is commonly impaired in MS, in the affected eye.

This test is similar to a standard eye chart performed at the eye doctor’s, where a person reads increasingly smaller lines of letters. In this test, however, there is low contrast between the white background and the letters, which are a faint gray instead of standard black.

These observed long-term clinical improvements … are unprecedented.

Top-line results showed CNM-Au8 led to significant improvements in LCLA performance over the placebo after a year. CNM-Au8 was also associated with stabilized brain structures, improvements in tests of dexterity and cognition, and a trend toward better walking ability.

After completing the main trial, 55 participants entered the VISIONMS-LTE (NCT04626921) extension phase, where all received CNM-Au8 (30 mg) for up to 96 more weeks, which totaled 144 weeks (nearly three years) of treatment for patients initially assigned to CNM-Au8 in the main trial.

Results now show that vision continued to improve for participants initially assigned to CNM-Au8, with LCLA scores increasing by 4 points (letters read) across both eyes since the end of the main trial at week 144. This amounted to a significant, 8.7-letter improvement from their pre-trial performance.

Individual participants saw sustained improvements by up to 38 letters across both eyes, which corresponds to being able to read multiple additional rows of letters on the eye chart, according to Clene.

Likewise, cognitive performance was significantly improved after 144 weeks of treatment, as assessed by the Symbol Digit Modality Test (SDMT). There, participants significantly improved by 8.03 points from the study’s start and by 3.11 points since the end of the main trial. Cognition improved by up to 35 points in individual participants, where a three-point change has been considered clinically meaningful in prior studies, according to Clene.

Other measures of mobility and dexterity observed in the main trial were maintained throughout the OLE.

Participants who switched to CNM-Au8 from the placebo experienced significant improvements in LCLA and SDMT performance that was comparable to gains seen for patients initially on CNM-Au8 in the main trial.

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No CNM-Au8-related serious adverse events reported in trial

The treatment was well tolerated with no treatment-related serious adverse events reported.

“These observed long-term clinical improvements … are unprecedented,” said Michael Barnett, PhD, a key clinical advisor for the VISIONARY-MS trial. Barnett is also a consultant neurologist at the Royal Prince Alfred Hospital and professor at the University of Sydney in Australia.

“Positive impacts on disease progression and the potential to at least partially reverse established disability, if confirmed in a larger study, represent a major therapeutic leap for patients with MS,” Barnett said.