Improved Cognition & Vision Exciting MS Clinical Trial Results | Rob Etherington Clip

Summary

The Visionary study explores the effects of AET-C8 in patients with stable relapsing-remitting Multiple Sclerosis (MS) and chronic optic neuropathy. Over a three-year period, the study assessed improvements in vision, cognition, and remyelination. Key findings include significant improvements in low contrast vision, cognitive function, and evidence of remyelination as indicated by visual evoked potentials and advanced MRI. These promising results suggest that AET-C8 could be a breakthrough in MS treatment, offering hope for enhanced quality of life and potential disease modification.

Takeaways

• 😀 The Visionary study is focused on remyelination in patients with relapsing-remitting Multiple Sclerosis (MS), particularly targeting visual and cognitive improvements.
• 😀 The study enrolled stable MS patients with chronic optic neuropathy, meaning they had vision impairment due to optic nerve damage but were otherwise stable with no recent MS flare-ups.
• 😀 Participants were randomized into two groups: one received active drug (AET C8) and the other received a placebo (purple-colored, tasteless water).
• 😀 The primary endpoint of the study was to assess improvements in low contrast visual acuity, specifically in low-light conditions, a common challenge for MS patients.
• 😀 Secondary endpoints included assessments of motor control, cognition, and other MS symptoms such as walking speed and ability to perform tasks like the 25-ft walking test.
• 😀 Visual Evoked Potentials (VEP) were used to assess remyelination by measuring signal latency and amplitude. Improvements in latency (signal speed) suggest remyelination.
• 😀 The study used advanced MRI techniques to measure the myelin water fraction, which helped assess the degree of remyelination in the cerebrum and other areas of the brain.
• 😀 Significant cognitive improvement was observed, with active drug recipients showing a 5-point improvement on the Symbol Digit Modality Test (SDMT) by the end of the double-blind phase.
• 😀 Over three years, the original active group showed a 7.5-point SDMT improvement, indicating substantial cognitive recovery.
• 😀 The placebo group, after transitioning to the active drug, nearly replicated the cognitive improvements of the original active group, demonstrating the efficacy of the drug in reversing cognitive impairment.
• 😀 The findings suggest that remyelination may be possible and could have a significant impact on both vision and cognition in MS patients, though further research in Phase 3 trials is necessary to confirm these results.

Q & A

What was the primary objective of the Visionary study?

The primary objective of the Visionary study was to assess whether the treatment AU8 (AET C8) could improve low-contrast visual acuity in patients with relapsing-remitting Multiple Sclerosis (MS) and chronic optic neuropathy.

How were patients selected for the Visionary study?

Patients were selected if they were stable relapsing-remitting MS participants with chronic optic neuropathy. They had to have been free of new MS lesions for at least six months, with the average being about three years, and were required to be on background disease-modifying therapies (DMTs).

What was the placebo used in the study?

The placebo used in the study was purple-colored water, which was designed to look and taste like the active drug (AU8) to maintain the study's blinding. It was created with a purple food dye that had no taste, ensuring the placebo could not be distinguished from the active drug.

What were the primary and secondary endpoints of the study?

The primary endpoint was the improvement in low-contrast visual acuity, measured by the ability to read a chart of letters. Secondary endpoints included assessments of motor control, cognition (using the Symbol Digit Modality Test), walking speed, and other functional abilities.

How was remyelination assessed in the study?

Remyelination was assessed using visual evoked potentials (VEPs) to measure the latency (speed) and amplitude (signal strength) of nerve signals from the eye to the visual cortex. Improved latency was associated with faster conduction velocity, indicating potential remyelination.

What did the MRI results indicate in the study?

The MRI results showed evidence of increased axonal integrity and reduced diffusivity in the brain, suggesting potential remyelination. This was measured using the myelin water fraction technique, which provides insights into changes in myelin content in the brain.

What was the effect of AU8 on cognition, as measured by the Symbol Digit Modality Test (SDMT)?

AU8 showed a significant improvement in cognition, with the active group improving by approximately five points on the SDMT by the end of the first year. Over the course of the entire three-year study, the original active treatment group saw a 7.5-point improvement. Patients who initially received placebo but switched to AU8 also showed similar cognitive improvements after starting the treatment.

What is the significance of the five-point improvement on the Symbol Digit Modality Test (SDMT)?

A five-point improvement on the SDMT is considered clinically meaningful, as it can represent a significant return to daily functional activities. For MS patients, it can be the difference between feeling cognitively foggy and being able to resume work and other mental tasks more effectively.

What were the results of the open-label phase of the Visionary study?

In the open-label phase, 90% of patients who completed the initial 12-month double-blind phase chose to continue on AU8. Those who had been on placebo during the double-blind phase and switched to AU8 showed similar cognitive and visual improvements as those who had been on AU8 from the start.

What are the next steps for the Visionary study?

The Visionary study will be followed by phase 3 trials to confirm the findings observed in this phase 2 study. These will further evaluate the efficacy of AU8 in promoting remyelination, improving cognition, and treating other MS-related symptoms.