OCS-05 neuroprotective therapy for MS shows good safety profile

OCS-05, a neuroprotective treatment candidate being developed by Oculis for multiple sclerosis (MS) or other causes of optic nerve inflammation, demonstrated a favorable safety and pharmacological profile in healthy volunteers, according to Phase 1 trial data.

A Phase 2 trial (NCT04762017), called ACUITY, is now evaluating OCS-05’s safety and effectiveness in people with acute optic neuritis due to MS, myelin oligodendrocyte glycoprotein antibody-associated disease, or an unknown cause.

Optic neuritis refers to inflammation of the optic nerve, which sends and receives signals between the eye and the brain. It’s a common symptom of MS.

ACUITY is seeking to enroll an estimate 42 adults, ages 18-60, at four sites in France. Eligible participants will have been diagnosed with acute optic neuritis affecting one eye and have had symptoms of vision loss occurring in the prior 12 days.

Findings from the Phase 1 trial were recently published in Scientific Reports, in a study titled, “A Phase 1 randomized study on the safety and pharmacokinetics of OCS-05, a neuroprotective disease modifying treatment for Acute Optic Neuritis and Multiple Sclerosis.”

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Good pharmacological, safety profile found for OCS-05 in healthy volunteers

MS is marked by the progressive loss of myelin, the fatty substance that surrounds and protects nerve cells, which ultimately causes nerve cells to malfunction and die off. When the optic nerve is affected by this process, it’s called optic neuritis.

Neuroprotective treatment strategies that can promote nerve cell health and myelin restoration (remyelination) are believed to hold significant promise for MS.

OCS-05, formerly known as BN201 or ACT01, is thought to activate a molecule called serum/glucocorticoid-regulated serum kinase 2 (SGK2), which elicits a range of downstream pathways that support nerve cell development, survival, and repair.

In particular, SGK2 induces the FOX03 molecule, which among several neuroprotective roles, can lead to increased activity of genes involved in the development of the cells that generate myelin. These cells are called oligodendrocytes.

Oculis believes its treatment may be promising for eye diseases involving neurological damage, including MS-associated optic neuritis. The company licensed OCS-05 last year from Accure Therapeutics.

Preclinical data indicate that the treatment candidate has neuroprotective and remyelinating properties, according to researchers, who say it also has the ability to protect against optic nerve damage.

Pharmacological studies also suggest the molecule has favorable properties, including a sustained presence in the bloodstream and an ability to reach brain tissue.

The Accure-sponsored Phase 1 study (NCT03630497) was designed to assess the safety, tolerability, and pharmacological properties of OCS-05 in 48 healthy adults.

Participants were randomly assigned to receive single or multiple doses of OCS-05 or a placebo, given as an into-the-vein (intravenous) infusion over a two-hour period.

In the first, single ascending dose part, participants were given a single infusion of OCS-05 at doses ranging from 0.05 to 3.2 mg/kg, or a placebo. A total of 32 people completed that part.

For the second part, 16 participants received either the placebo or OCS-05 at a dose of either 2.4 or 3 mg/kg for five consecutive days.

Across both parts, most side effects were mild, transient, and considered unrelated to treatment. The most common side effects were pain and upper respiratory infections.

No significant cardiac events were observed, nor were there any abnormalities of concern in blood or brain evaluations.

The treatment also showed a good pharmacological profile, with concentrations in the bloodstream generally reaching their highest levels two hours after starting the infusion — around the time the infusion period was ending.

With multiple doses, the treatment did not accumulate in the bloodstream, and always remained below safety thresholds.

Overall, OCS-05’s safety and pharmacological properties support “testing it as a neuroprotective therapy for [acute optic neuritis] and MS,” the researchers wrote.

Based on those findings, the researchers determined the starting dose for the Phase 2 trial in that patient group would be 2-3 mg/kg. Participants will be randomly assigned to receive OCS-05 or a placebo for five consecutive days and will be monitored for up to six months.

In addition to safety, the trial will assess changes in eye health, visual acuity, and overall disability.

Initial results from ACUITY are expected later this year.