Gold nanocrystals may be effective as adjunctive MS therapy

The results of the VISIONARY-MS study suggest that an oral suspension of catalytically active gold nanocrystals (CNM-Au8^®) given in addition to disease-modifying therapy (DMT) is effective in patients with stable relapsing multiple sclerosis (RMS). Not only vision but also global neurological function was improved.

First author Prof. Michael Barnett (University of Sydney, Australia) started by recognising an unmet need: “Despite the availability of a large number of highly effective DMTs, we still do not have a therapy that promotes remyelination, and we certainly do not have a proven neuroprotective therapy for MS” [1].

CNM-Au8 is hypothesised to restore neuronal health and function by supporting brain energy metabolism. The catalytically active nanocrystals of CNM-Au8 are assumed to drive critical cellular energy, which produces reactions that enable neuroprotection and remyelination by increasing neuronal and glial resilience to disease-relevant stressors. In preclinical models, this resulted in neuroprotection and remyelination.

The current phase 2 VISIONARY-MS trial (NCT03536559) was designed as a multicentre, randomised, double-blind study evaluating CNM-Au8 versus placebo over 48 weeks in participants with stable RMS [2]. Participants were randomised 1:1:1 to CNM-Au8 15 mg/day, 30mg/day, or placebo. Prof. Barnett said the study was terminated prematurely because recruiting participants during the COVID-19 pandemic proved too challenging. Of the 150 planned participants, 73 were randomised. The participants were between 18 and 55 years of age, had RMS since <15 years, were clinically stable over the prior 6 months, and had chronic optic neuropathy, with a best corrected-low contrast letter acuity (BC-LCLA, using 2.5% low-contrast Sloan letter chart) of 20/40 or worse in the affected eye. The primary endpoint was a change in BC-LCLA score in the most affected eye up to week 48. The secondary endpoint was a global neurological improvement, measured by the modified MS functional composite (mMSFC) change up to week 48.

Both the primary and secondary clinical endpoints significantly improved (see Figure). The BC-LCLA change in the affected eye significantly differed as early as week 24. At week 48, the least squares mean difference was 3.13 (95% CI -0.08 to 6.33; P=0.056). In the CNM-Au8 group, global neurological improvement at week 48 was also more favourable than in the control group, with the least squares mean difference of 0.28 (95% CI 0.05–0.51; P=0.0197). The positive result of the latter endpoint was mainly driven by changes in LCLA in both eyes, in the Symbol Digit Modalities Test and the 9-Hole Peg test of the dominant hand. Prof. Barnett added that CNM-Au8 also improved independent quantitative biomarkers of enhanced axonal integrity, namely multifocal visual evoked potential amplitude and fractional anisotropy. CNM-Au8 was safe and well-tolerated; treatment-emergent adverse events were mild-to-moderate and transient.

Figure: CNM-Au8 improves the primary and secondary clinical endpoints [1]



LCLA, low contrast letter acuity; LS-mean, least squares mean; 9HPT, 9-Hole Peg test; SDMT, Symbol Digit Modalities Test; mITT, modified intention-to-treat; SEM, standard error of the Mean.

1. Robinson AP, et al. Sci Rep. 2020;10(1):1936.
2. Barnett M. VISIONARY-MS top-line results: A Phase 2, randomized, double-blind, parallel group, placebo-controlled study to assess the safety and efficacy of CNM-Au8, a catalytically active gold nanocrystal suspension in relapsing multiple sclerosis.PL5.005, AAN 2023 Annual Meeting, 22–27 April, Boston, USA.

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Posted on 26 June 20236 September 2023