CNM-Au8 Displays Positive Interim Results in Multiple Sclerosis

Robert Glanzman, MD

Interim data from the phase 2 VISIONARY-MS trial (NCT03536559) suggest that Clene Nanomedicine’s investigational nanocatalytic agent CNM-Au8 demonstrates potential as a promoter of neurological improvement in patients with stable multiple sclerosis (MS) who are currently on disease-modifying therapy (DMT).^1,2

The analysis showed that patients treated with CNM-Au8 with an Expanded Disability Status Scale (EDSS) score of 2.0 or higher experienced clinically relevant improvements on a number of modified MS Functional Composite (MSFC) subscales compared with those patients with EDSS scores of 1.5 or lower, or the most mildly affected patients.¹

The data were presented virtually at the Americas Committee for Treatment and Research in Multiple Sclerosis (ACTRIMS) Forum 2021, February 25-27, by Robert Glanzman, MD, FAAN, chief medical officer, Clene Nanomedicine.

“The takeaway here is that we’re seeing a brand-new therapeutic category,” Glazman told NeurologyLive. “No one has been able to actually have nanocatalysts—we’re directly donating and receiving electrons to and from biological systems, and not just a few electrons, but thousands. I think [CNM-Au8] holds tremendous promise for all kinds of neurodegenerative diseases, including progressive MS.”

Glanzman added that the clinical community should be on the lookout for when the company eventually reveals unblinded data down the road for this therapy. He noted that VISIONARY-MS, while still ongoing, has faced a number of delays due to the ongoing pandemic like many other clinical trials, and hopes to resume enrollment in the later part of 2021.

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Those in the EDSS 2.0 or higher group experienced improvements equating to nearly 0.5 standard deviation (SD) above the baseline value for the most mildly affected patients, who were the comparator group, in the Symbol Digital Modalities Test (SDMT; P <.0001) as well as in Best Corrected Low-Contrast Letter Acuity (BC-LCLA; P = .0071). Additionally, improvements were observed in the 9-Hole Peg Test (9HPT) non-dominant (P = .0050) and in the Timed 25-Foot Walk test (T25W; P not significant).

The change in the 6-component MSFC z-score—which included the SDMT, LCLA in both eyes, 9HPT with both dominant and nondominant hands, and T25W—was significantly improved for those with EDSS 2.0 or higher compared to the EDSS 1.0 or lower group (P = .0005).

In total, the 52 patients in the trial are on a number of DMTs, with 52% (n = 27) on a monoclonal antibody (alemtuzumab, natalizumab, rituximab, and ocrelizumab), 36.5% (n = 19) on an oral therapy (fingolimod, dimethyl fumarate, teriflunomide, thyroxine, and oral combinations), and 4% (n = 2) on an injectable (glatiramer acetate). The remaining 8% (n = 4) of patients were not actively on a DMT. The mean overall baseline EDSS score was 1.8 (SD, 1.5), with an average time from MS onset being 6.0 years (SD, 3.8).

Additionally, Clene presented preliminary results from the REPAIR-MS clinical trial (NCT03993171) which offer the first clinical evidence that demonstrates the catalytic effects of CNM-Au8 on key bioenergetic metabolites in MS (and Parkinson disease) brains. Those data revealed that the therapy increases the NAD+/NADH (nicotinamide adenine dinucleotide) ratio and AT (adenosine triphosphate) levels, as measured by percent change.³

Glanzman and colleagues noted that the brain metabolic homeostasis observed with CNM-Au8 treatment may be neuroprotective; this hypothesis is currently being explored in both VISIONARY-MS and REPAIR-ALS phase 2 and Healey ALS Platform phase 3 studies. Full analyses of those data are expected to be conducted once the trials are completed.

“As VISIONARY-MS and REPAIR-MS continue to progress, we see consistent and complementary results,” Glanzman said in a statment.² “Interim data from the REPAIR-MS program provide further evidence for CNM-Au8 to enter the brain and reverse bioenergetic failure, a key driver in the pathophysiology of MS and other neurodegenerative diseases.”

VISIONARY-MS, Clene noted in its release, represents the first efficacy study for a completely novel therapeutic category. CNM-Au8 is a nanotherapeutic agent designed to provide bioenergetic, catalytic support to neurons and oligodendroglia precursor cells for neuroprotection and improved remyelination in MS.

“These mechanistic results provide important support for the updated, blinded interim VISIONARY data analysis, which suggest that CNM-Au8 has the potential to drive clinically meaningful improvements in recognized MS functional endpoints when administered in addition to standard of care,” Glanzman continued in the statement. “We look forward to the continued advancement of these trials.”

For more coverage of ACTRIMS Forum 2021, click here.

REFERENCES
1. Glanzman RL, Beadnall H, Barnett M, et al. VISIONARY-MS: Update to a Phase 2 clinical trial of catalytic gold nanocrystals, CNM-Au8, for the treatment of chronic optic neuropathy. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Abstract P050.
2. Clene Nanomedicine Presents Updated Interim Data from Phase 2 Multiple Sclerosis Programs at ACTRIMS Forum 2021. News release. February 25, 2021. Accessed February 26, 2021. https://finance.yahoo.com/finance/news/clene-nanomedicine-presents-updated-interim-123100727.html
3. Glanzman RL, Rin J, Greenberg B, et al. Effects of Nanocatalysis on CNS Bioenergetic Markers in Patients Treated with CNM-Au8: Interim Results from Two Phase 231Phosphorous Imaging Studies. Presented at ACTRIMS Annual Forum; February 25-27, 2021. Abstract P043.