AAN 2024 | CNM-Au8 improves visual function in MS: insights from the VISIONARY-MS trial

CNM-Au8 is a novel therapy. Essentially, it’s a suspension of gold nanocrystals. Each dose contains about 1.2 quadrillion nanocrystals. And these are both brain penetrant and cell membrane penetrant, so they get into all cells in the body, including neurons. The proposed mechanism of action of this drug is to enhance the cellular energetics. Essentially, the surfaces which are clean, faceted surfaces of these nanocrystals act as a catalyst primarily in the conversion of NADH to NAD+. By improving that ratio, it will result in more ATP in the cells, and ATP is of course, the primary energy source of most of the cells, including neurons. So the idea is to improve cellular energetics in neurons that might be susceptible to death in a variety of diseases. Multiple sclerosis (MS) is the topic of interest in the VISIONARY-MS study, but this idea could be used across a broad spectrum of other neurodegenerative disorders.

VISIONARY-MS is a Phase II study in patients with relapsing multiple sclerosis who are stable and have chronic optic neuropathy at baseline. The idea of this therapy is to see whether or not we can promote remyelination and potentially axonal function improvements in a patient group by treating them with this drug. It was a placebo-controlled trial with the double-blind period lasting for 48 weeks. The long-term extension data takes patients out to about three years of treatment altogether. The primary clinical outcome of the study was a change in low contrast letter acuity from baseline (which is a clinical measure). There were also paraclinical measures to support improvements in visual function, namely multifocal visual evoked potential amplitude and latency. That gives us an idea of axonal function and myelination status of the optic nerve, respectively. In addition, there were nonvisual outcomes that speak to the more global effect of the drug; namely measures such as cognition with the SDMT and other measures such as timed 25-foot walk, etc.

The long-term follow-up essentially showed the same trends we saw in the earlier study, but showed now significant improvements to baseline across a range of both paraclinical measures and clinical measures. Paraclinical measures are the ones I spoke to before. Firstly, evidence of remyelination, namely a reduction in the latency of the visual evoked potential (faster conduction consistent with remyelination), the improved amplitude, which was for me an unexpected finding of the visual evoked potential which spoke to improved axonal function, and namely the primary outcome of the double-blind phase: the low contrast letter acuity. This continued to improve over the course of the study and remained significant out to the end of the study. Similarly, we saw changes that reflected that same trend, with significant benefits over baseline for SDMT as well. We have now a range of paraclinical measures and clinical measures that have improved over this study.

Now, it’s a small, Phase II study. It was conducted (at least the double-blind phase), during the pandemic, so it didn’t recruit to the same level we wanted. But despite that, I think it’s a remarkable study in the sense that we’ve got not just paraclinical measures, but measurable clinical benefits that corroborate those changes. Personally, I would love to see a Phase III study. I think there’s more than sufficient data there now to justify a Phase III study. These results have provided incredible impetus for that. But that’s a question for Clene Nanomedicine, and obviously I’m sure they are looking forward to a Phase III study. We would love to get that off the ground as soon as we can.