OCS-05 shows safety, aids vision with optic neuritis in Phase 2 trial
Treatment at 3 mg/kg infused daily for 5 days improved nerve thickness, sight
OCS-05, an experimental medication that Oculis is developing to treat acute optic neuritis, a common symptom of multiple sclerosis (MS) that can lead to vision loss, was well tolerated and improved measures of vision and eye health in a Phase 2 clinical trial.
The ACUITY study (NCT04762017) included people whose optic neuritis was caused by MS or other demyelinating disorders. Their first symptoms of vision loss had started in the past 12 days, and they were given OCS-05 or a placebo on top of standard-of-care steroids.
“These positive safety and efficacy results from ACUITY represent a significant milestone in bringing the first potential neuroprotective treatment in ophthalmology to patients,” Riad Sherif, MD, CEO of Oculis, said in a company press release.
Optic neuritis affects up to 70% of MS patients at some point
MS is characterized by inflammation in the brain and spinal cord that damages myelin, a protective sheath around nerve fibers. In many patients, this can lead to optic neuritis — inflammation of the nerves that carry signals from the eyes to the brain.
Optic neuritis is often one of the first signs of MS, and is experienced by up to 70% of patients at some point in their lives. It can lead to problems with vision, ranging from blurred vision to a complete loss of sight, which usually worsen over a few hours to days.
OCS-05 is an investigational nerve-protecting agent designed to treat optic neuritis associated with MS and other similar diseases marked by myelin loss. A previous Phase 1 study in healthy volunteers showed a good safety profile for OCS-05.
In the ACUITY trial, 33 people with acute optic neuritis in one eye caused by a demyelinating disorder were randomly assigned to receive OCS-05 — infused at doses of 2 or 3 mg/kg — or a placebo, daily for five days. All patients also received steroids.
“Steroids have been used to treat the inflammation seen in acute optic neuritis, but don’t prevent persistent visual impairments or reduce structural loss,” said Mark Kupersmith, MD, a professor at Mount Sinai Hospital in New York. “There remains a critical unmet need for neuroprotective therapies to preserve vision.”
Reasonable safety, vision gains reported in patients treated with OCS-05
The study’s main goal was to evaluate safety, especially heart-related safety. Findings showed that two patients given OCS-05 and one on the placebo had abnormal heart rate readings at any point. However, in both patients on OCS-05, the changes were mild, temporary, and judged by clinicians as not clinically significant.
There also were no serious side effects related to OCS-05 reported during the study; the therapy’s most common side effects were acne and headache.
ACUITY assessments also included measures of eye health and visual function. Specifically, researchers used a technique called optical coherence tomography (OCT) to evaluate the thickness of the nerves at the back of the eye — in optic neuritis, these nerves tend to get thinner due to the inflammatory damage to the optic nerve. Patients also underwent a test of visual function called low contrast vision acuity (LCVA), which evaluates how well patients can read faint grey letters on a white background.
Results showed that, relative to a placebo, the higher dose of OCS-05 led to improvements in nerve thickness measured by OCT. At three months post-treatment, the thickness of a group of nerve cells called the ganglion cell-inner plexiform layer showed a relative increase of 43%, while the thickness of another group of nerves called the retinal nerve fiber layer was increased by 28%. These increases were sustained or improved slightly out to six months following treatment.
In LCVA measures, patients given the high dose of OCS-05 were able to read about 18 more letters than those given a placebo at three months post-treatment. At six months, there was still a significant difference between the groups of about 15 letters.
FDA clears way for possible clinical trial of therapy in US
“The improvement in vision is especially encouraging, and the consistent improvement in retinal structure highlights the therapeutic potential of OCS-05 across multiple ophthalmic and neurological conditions,” Sherif said. “We are excited to further advance OCS-05’s development in acute optic neuritis, while actively exploring its potential in additional neuro-ophthalmic indications with the aim to deliver a first-in-class neuroprotective treatment option to patients.”
OCS-05 has received orphan drug status in both the U.S. and Europe. These designations aim to accelerate the development of treatments for rare diseases by offering incentives such as fee exemptions and several years of marketing exclusivity upon approval.
The ACUITY study was conducted at sites in France, but the U.S. Food and Drug Administration has recently given clearance for Oculis to start clinical testing of OCS-05 in the U.S.
“I look forward to the additional studies that can now be initiated for acute optic neuritis while further exploring the full potential of this promising neuroprotective candidate in both ophthalmology and neurology indications,” said Pablo Villoslada, MD, a member of Oculis’ scientific advisory board and chair of the neurology department at Hospital del Mar, Pompeu Fabra University, in Barcelona, Spain.
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