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DENVER -- An oral suspension of clean-surfaced gold nanocrystals known as CNM-Au8 was safe and well-tolerated in patients with stable relapsing-remitting multiple sclerosis (MS) and chronic optic neuropathy, the long-term open-label extension of a phase II trial showed.

At week 144, six serious adverse events were reported among 55 participants, all of which were determined to be unrelated to the investigational treatment, said Michael Barnett, MBBS, PhD, of the University of Sydney in Australia, during an Emerging Science session at the American Academy of Neurology (AAN) annual meeting.

Treatment-emergent adverse events were transient and mostly mild to moderate, Barnett noted. Most common were upper respiratory tract infection, headache, and urinary tract infection. Improvements also were observed across cognitive and visual endpoints, he added.

The assessed the long-term safety and efficacy of 30 mg daily CNM-Au8 on participants over 96 weeks after the 48-week double-blind phase II VISIONARY-MS trial. The phase II data, presented at last year's AAN meeting, showed that CNM-Au8 improved low-contrast letter acuity () by 3.13 letters relative to a placebo group (P=0.056). LCLA served as the efficacy endpoint.

In the extension study, the mean difference at week 144 for LCLA change from baseline across both eyes was +8.7 letters (95% CI 5.0-12.4, P<0.0001) for people who started with CNM-Au8 in the 48-week double-blind period. On the (SDMT), a measure of working memory and cognition with a maximum score of 110, the mean difference at week 144 for the CNM-Au8 group was +8.03 points (95% CI 5.01-11.0, P<0.0001).

Nearly all participants (92%) in the phase II study were on background disease-modifying therapies. The extension study enrolled 41 participants from the phase II study who started on CNM-Au8 and 14 participants who started on placebo. The modified intention-to-treat analysis included 35 and 11 participants, respectively.

The findings -- from a small clinical trial with an "incompletely understood" mechanism -- should be interpreted with caution, noted Robert Bermel, MD, of the Cleveland Clinic, who wasn't involved with the research.

"The clinical effect is really minimal," Bermel said in an interview with MedPage Today. "These trials are not designed to show a large clinical effect in people; [they're] designed to show a scientific proof of concept that could potentially get a compound or a mechanism to the next step."

"The field of MS therapeutics has had great success modulating the immune system and preventing MS damage," Bermel pointed out. "Over the last two decades, we've gotten really good at that, and we have highly effective therapies now to prevent new immune damage."

But the field has not been able to improve function that's already lost, he observed. The CNM-Au8 studies may be trying to do that -- "turn back the clock a little bit," he noted.

Preclinical studies suggest that gold nanocrystals and the nicotinamide adenine dinucleotide (NAD) pathway, possibly preventing neuronal axons from degrading and allowing for remyelination.

The role of gold in medicine spans centuries and includes injections of gold compound sodium aurothiomalate to treat rheumatoid arthritis, but many gold treatments have recently fallen out of favor. "Unlike old gold therapies that we used to use for things like rheumatoid arthritis, which had lots of side effects ... [CNM-Au8] is pure gold nanocrystals. It's got a very clean safety profile with no real side effects," Barnett told MedPage Today.

In and its extension study, other outcomes included paraclinical biomarker data. Multifocal visual evoked potential (VEP) amplitude findings suggested "an early improvement in the double-blind phase of the study that's been sustained out toward the end of the study for patients beginning and maintained on CNM-AU8," Barnett said. VEP latency also appeared to improve: "By 96 weeks, there was about a one millisecond improvement in the multifocal VEP latency in those patients who began on drug and were maintained on it," he added.

Optical coherence tomography showed that ganglion cell layer "was preserved essentially for both the patients who began on drug and those patients who transitioned to drug, ending at around baseline in both cases," Barnett noted. MRI diffusion tensor imaging suggested improvements on chronic T2 lesions that reached significance out to 96 weeks; the graphs "come together toward the end -- but remember, there are very few patients out to 144 weeks," he said.

CNM-AU8 also is being studied in (ALS) and Parkinson's disease. The VISIONARY-MS findings support a phase III trial in MS, Barnett said.

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