Topical DME drug shows promise in Phase II trial

A novel eyedrop formulation of dexamethasone was found to reduce swelling and improve vision in a Phase II trial of patients with diabetic macular oedema (DME).

A novel eyedrop formulation of dexamethasone was found to reduce swelling and improve vision in a Phase II trial of patients with diabetic macular oedema (DME). The proof-of-concept study evaluated the efficacy of the drug, OCS-O1, in development by biopharmaceutical company Oculis, based on the change to central macular thickness (CMT) and best-corrected visual acuity (BCVA) at the end of 12 weeks when compared with a vehicle eye drop. The drug led to a statistically significant decrease in CMT and it also improved best-corrected visual acuity (BCVA), according to a company press release.

OCS-01 uses Oculis’ proprietary soluble nanoparticles technology, which acts to increase the drug concentration in the formulation without affecting lipophilicity, according to the firm. It is designed to improve the contact time on the eye surface through interaction with the mucous layer, and to enhance the lipophilic drug delivery through high and prolonged concentrations in the tear film, to help it permeate the lipid membrane.

Randomised trial

The trial (DX-211) was a randomised, multi-centre, prospective, parallel group, double-masked study of 133 patients. All suffered from type 1 or 2 diabetes with a CMT of ≥ 310 µm as determined by spectral domain optical coherence tomography (SD-OCT) and BCVA letter score ≤ 73 and ≥ 24. Participants were aged 18-to-85 years and had had suffered from DME for fewer than three years.

Study participants were randomised to receive either OCS-01 or matching vehicle eye drops. Two patients were assigned to the OCS-01 group for every one patient assigned to the vehicle group.

The eye drops were applied at a rate of one drop per dose, three times a day for 12 weeks. Patients were monitored for an additional four weeks following the completion of their treatment.

After 12 weeks, mean CMT decreased 53.6 μm in the OCS-01 group, compared with 16.8 μm in the vehicle group (p = 0.0115). BCVA improved by 2.62 early treatment diabetic retinopathy study letters in the OCS-01 group versus 1.04 letters in the vehicle group (p = 0.125; the conventional threshold of statistical significance is p < 0.05).

There were 45 patients with a baseline BCVA of 65 or less in the OCS-01 group and 14 in the vehicle group. In this subgroup, CMT decreased by 77.4 μm in the OCS-01 group, compared with 23.1 μm in the vehicle group. BCVA improved by 3.8 letters in the OCS-01 group compared with 0.9 letters in the vehicle group.

Administered as an eye drop, OCS-01 is less invasive than current treatments for DME, according to principal investigator Pravin U. Dugel, chairman of Oculis’ Scientific Advisory Board, and a clinical professor at the University of Southern California in Los Angeles, United States. He presented the findings at the Angiogenesis, Exudation and Degeneration conference in Miami, Florida.

“The current standard of care involves intravitreal injections, and this has a marked negative impact on patient compliance, accessibility and treatment sustainability,” said Dr Dugel in the company press release. “OCS-01 as a topical drug presents a truly innovative, non-invasive approach that has the potential to change the treatment paradigm in DME, and one that would be welcomed by physicians and patients alike.”

Previous topical treatments have not succeeded as a treatment for DME because of limited solubility in formulation, a short contact time on the eye surface and inability to penetrate the lipid membrane barrier of the eye wall, Dr Dugel said.

Researchers did not observe any significant adverse effects of the treatment and reported similar levels of local ocular tolerability when comparing the OCS-01 and the vehicle group, with the exception of intraocular pressure (IOP.)

Researchers reported that IOP increases were more common with OCS-01 than with the vehicle during the treatment period. These increases were consistent with known dexamethasone effects, they said.