Clene has presented updated trial results for its Visionary MS Phase II clinical trial for its lead pipeline candidate, CNM-Au8. The trial is investigating CNM-Au8 as a treatment for patients with relapsing forms of multiple sclerosis (MS) with chronic optic neuropathy. The agent has a first-in-class mechanism of action within the MS portfolio, as it is a first drinkable treatment based on a nanocrystalline gold suspension that has reached late-stage development for MS.

In comparison to currently marketed and late-stage pipeline MS agents, CNM-Au8 doesn’t target disease progression, nor relapse rate. The Visionary trial has exclusively enrolled MS patients with chronic optic neuropathy, in which progression of MS leads to damage of the optic nerve. The main endpoints of the Phase II trial are to investigate visual functions and neurological functions (such as measures of visual function, visual evoked potential, changes in the MS functional composite) induced by remyelination and neuroprotection of the brain and spinal cord. Among this patient subset, CNM-Au8 would therefore be positioned as an adjuvant therapy to other existing treatments, which are administered with the aim of slowing MS progression.

Topline results of the Visionary trial (NCT03536559) were presented by the company in August last year, showing a significant improvement in the low contrast letter acuity (LCLA) score relative to placebo (least squares mean difference of 3.13) after 48 weeks. This means that the patients’ contrast sensitivity led to an improvement, helping them to distinguish between an object and its background. Updated results from the Visionary trial then demonstrated a significant improvement in multi-focal visual evoked potential (mfVEP) across both eyes by a mean difference of 7.9%, relative to placebo, after 48 weeks. As mfVEP serves as a biomarker of the myelination in the visual pathway, these results provide evidence that CNM-Au8 improves and increases information transmission in the visual system, supporting the improved axonal integrity. This is the first time a disease modifying therapy (DMT) targeting vision decay specifically in MS has demonstrated such data.

It is refreshing to see a treatment where its primary purpose is not to improve progression of the disease itself, but to support remyelination in MS patients, restoring lost function of myelin. Improving nerve cell function and survival can help MS patients in a broad range of problems, such as vision improvement, as chronic vision problems are a common symptom during MS, experienced by around one in five patients. In this subset, CNM-Au8 therefore has promising potential as an adjacent therapy for patients who are already on DMTs to reduce MS progression and relapses, especially as the agent exhibits a good safety profile, with most common side effects being headache, upper respiratory infection, and sore throat.

While the initial clinical data seems promising for CNM-Au8, key opinion leaders (KOLs) interviewed by GlobalData are not completely convinced about the agent as yet. Although they expect CNM-Au8 to be an interesting addition to the MS portfolio, they would like to see more mechanistic data and clear overall benefits that the agent could bring to patients.

This may partly reflect the limited sample size of the Visionary trial, which achieved enrollment of only 72 patients out of an expected 150, due to Covid-19 pandemic complications, leading to the pre-specified significance threshold at p=0.1 before the submission to the FDA. The Phase III study would therefore need to demonstrate strong mechanistic data and the overall positive impact of the agent, through a larger patient cohort and strong statistical significance in comparison to placebo, for the KOLs to recommend the agent to their patients. Nonetheless, the agent is a promising asset to the MS portfolio, due to its unique targets and its potential to address an unmet need in MS.

Clene is exploring many potential uses of the CNM-Au8 agent. Not only it is running another CNM-Au8 phase II clinical trial for MS (NCT03993171), focusing on improving brain function and protection against cell death, but the agent is also undergoing clinical trials for amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD). In ALS, CNM-Au8’s Phase II clinical trial (NCT04098406) failed to meet its primary and secondary endpoints, which were focused on reducing mortality, across the combined 30mg and 60mg doses of CNM-Au8. However, the 30mg dose alone demonstrated improved survivability and will therefore be investigated further in an upcoming clinical trial. As for PD, CNM-Au8 demonstrated improvements in the brain’s energetic profile, through the protection against cell death, in the Phase II REPAIR-PD clinical trial (NCT03815916).