CNM-Au8 Lessens Vision Problems in RRMS Patients in Phase 2 Trial
VISIONARY-MS results show Clene's oral therapy supports remyelination
CNM-Au8, Clene Nanomedicine’s experimental oral therapy, safely and effectively improves vision and neurological function in adults with stable relapsing-remitting multiple sclerosis (RRMS) and disease-related visual impairment.
Those are the findings of the VISIONARY-MS Phase 2 clinical trial (NCT03536559), a proof-of-concept study that investigated CNM-Au8 in people with multiple sclerosis (MS) who have vision problems.
While the trial ended prematurely due to pandemic-related challenges — limiting the number of participants to 73 from the planned 150 — the results nonetheless provide “physiological evidence for [CNM-Au8’s] potential neuroprotective and remyelinating effects,” Clene stated in a press release.
“The MS community has been successful at limiting relapses, but we need therapies to address progression independent of relapse activity,” said Benjamin Greenberg, MD, one of the trial’s clinical advisers.
The VISIONARY-MS study was designed to establish that restoring brain cells’ energetic balance with CNM-Au8 “can support remyelination and neuroprotection in people living with MS,” Greenberg said.
Remyelination refers to the repair of myelin, the protective sheath around nerve fibers that is progressively lost in people with MS. It is a key goal of MS care, as it has the potential to restore lost function.
“These data are very encouraging to us in the MS research and treatment community as we work to address functional improvement in patients,” added Greenberg, also a professor of neurology at the University of Texas Southwestern Medical Center.
CNM-Au8 is an oral liquid suspension of gold nanocrystals designed to enter the brain and spinal cord and improve nerve cell survival and function. It does so by supporting the cells’ energy needs while lowering oxidative stress, a type of cellular damage implicated in MS and other neurodegenerative diseases.
A pilot open-label Phase 2 trial, called REPAIR-MS (NCT03993171), previously tested CNM-Au8 in 11 RRMS patients. REPAIR-MS showed that 12 weeks or about three months of daily treatment boosted energy metabolism in participants’ brains.
Based on these findings, Clene opened the study to people with nonactive progressive MS, meaning those with primary progressive or secondary progressive MS who had no history of relapses or new inflammatory brain lesions in the past five years. The study is expected to finish by year’s end.
Treating vision problems in MS
The VISIONARY-MS Phase 2 trial evaluated the safety and effectiveness of CNM-Au8 against a placebo in 73 stable RRMS patients, ages 18 to 55. All had chronic vision problems due to MS — a common symptom among people with the disease.
Participants were randomly assigned to receive a liquid formulation of either 15 or 30 mg of CNM-Au8, or a placebo. Treatment was given daily for 48 weeks (nearly one year). More than 90% of the patients also were receiving standard disease-modifying therapies (DMTs).
Due to limited enrollment, the threshold for statistical significance regarding group differences was pre-specified at a slightly higher value than the standard.
The primary analysis excluded specific data from 10 patients — namely, vision scores from nine individuals and a walking function score from one patient. The data on the MS patients with vision problems came from a single center with testing errors. Meanwhile, the walking function scores assessed one patient who changed a mobility assist device from a cane to a walker during the trial.
According to Clene, results from whole-data analysis followed similar trends, but did not reach statistical significance.
Top-line data showed that CNM-Au8-treated patients showed a significant improvement in low contrast letter acuity (LCLA) in the affected eye compared with those on a placebo — meeting the trial’s primary goal. LCLA is an eye exam chart with low contrast between the letters and the background that assesses visual disability in MS.
“We focused on vision as the primary endpoint in this study because it is a sensitive measure that reflects the functioning of the entire central nervous system,” Robert Glanzman, MD, Clene’s chief medical officer, said in a company webcast announcing the results.
The study also met a secondary goal of showing that CNM-Au8 was significantly superior to a placebo at improving neurologic function, as assessed with the modified Multiple Sclerosis Functional Composite (mMSFC) scale.
This measure includes LCLA for vision function, the symbol digit modalities test for cognitive abilities, the 9-hole peg test for arm and hand function, and the timed 25-foot walk to assess walking skills.
Findings of VISIONARY-MS trial
CNM-Au8 also was associated with a greater proportion of patients showing repeated clinical improvement (45% vs. 29%), meaning individuals who experienced a 15% or greater improvement in at least two mMSFC domains over the 48 weeks. The data, however, was “not statistically significant, likely due to compromised enrollment and insufficient power,” Glanzman said in the webcast.
Consistent improvements favoring CNM-Au8 also were observed across multiple biomarkers of myelin integrity and remyelination, including eye tests and MRI parameters. In contrast, participants in the placebo group generally worsened across these measures during the 48-week period.
“These data provide independently assessed quantitative physiological evidence that supports the potential neuroprotective and remyelinating effects of CNM-Au8,” Clene stated in the release.
In addition, the experimental therapy was generally safe and well-tolerated, without significant safety findings. The company expects to share VISIONARY-MS’s full dataset at an upcoming scientific congress.
“In this study, CNM-Au8 demonstrated neurological improvements in people with stable relapsing MS as adjunctive therapy to immunomodulatory DMTs,” Glanzman said in the release.
After completing VISIONARY-MS, participants could choose to enter its open-label extension study (NCT04626921), in which all are receiving 30 mg of CNM-Au8 daily for up to two years.
“These results further demonstrate the potential of CNM-Au8 to drive neuronal cellular energy production in patients struggling with MS and other neurodegenerative diseases,” said Rob Etherington, Clene’s CEO and president.
Based on these promising findings, Clene plans to initiate “a Phase 3 clinical program in people with MS who are experiencing progression independent of relapse activity, the most urgent unmet medical need in MS today,” Glanzman said.
“We look forward to the next phase of clinical development,” Glanzman added.
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