Topline Results from Phase 3 DIAMOND Trial Suggest Efficacy of Topical OCS-01 for DME

The phase 3 DIAMOND trial met its stage 1 objective of validating the optimal dosing regimen of topical OCS-01 with statistical significance in patients with diabetic macular edema (DME), according to a release from Oculis.¹

The positive topline results indicate the OCS-01 study arm met its primary efficacy endpoint of mean change in best-corrected visual acuity (BCVA) versus baseline at Week 6 with a statistically significant improvement compared to the vehicle arm. Meanwhile, secondary endpoints indicate a higher percentage of patients achieved a ≥15-letter improvement in BCVA and more improvement in retinal thickness as measured by central subfield thickness (CST) when treated with topical OCS-01.

“As a co-principal investigator of the phase 3 DIAMOND trial, it is exciting to see the positive stage 1 results from this trial,” Arshad M. Khanani, MD, MA, director of clinical research at Sierra Eye Associates and clinical associate professor at the University of Nevada, Reno School of Medicine said in the statement. “A 7.2 letters improvement in BCVA and a 63.6 µm reduction in CST at 6 weeks after initiating topical treatment with OCS-01 in patients with DME is clinically meaningful for treating physicians and patients. As a non-invasive treatment that has shown these positive results, OCS-01 has the potential of benefitting a large number of patients with DME if approved.”

The leading cause of vision loss worldwide, as well as legal blindness in those with diabetes, DME affects nearly 37 million people, with a significant number left untreated resulting from a lack of convenient treatment options. Due to this, the positive phase 3 stage 1 topline results on OCS-01 could represent a paradigm shift for patients with DME. The drops are a novel, high-concentration (15 mg/ml) formulation of dexamethasone and utilize the company’s Optireach® technology.

OCS-01 is developed to reach the retina via an eye drop, while most treatments for DME require a more invasive procedure, including ocular implants or intravitreal injections to deliver medication to the retina. According to the company, the Optireach® solubilizing formulation technology can address the limitations of conventional eye drops by improving the solubility of lipophilic drugs, increasing the residence time on the eye surface, and allowing the drug passage from the eye surface to the posterior segment of the eye.

“The mechanism of DME involves both increased permeability and inflammation,” David S. Boyer, MD, co-principal investigator for DIAMOND and adjunct clinical professor of ophthalmology, Keck School of Medicine, University of Southern California said in the statement. “Current anti-vascular endothelial growth factors (anti-VEGFs) are effective as anti-permeability agents but have no effect on inflammation. Therefore, a significant proportion of patients are sub-optimally treated with anti-VEGFs alone. If approved, OCS-01 has the potential to complement current treatment and address recalcitrant patients.”

DIAMOND is a phase 3, two-stage, double-masked, randomized, multicenter trial designed to assess the efficacy and safety of OCS-01 eye drops in patients with DME. Stage 1 was conducted in 39 sites across the United States and Europe with 148 patients randomized 2:1 to receive OCS-01 (n = 100) or vehicle (n = 48) 6 times daily for a 6-week loading phase and 3 times daily for a 6-week maintenance phase.

Results from stage 1 of DIAMOND suggest OCS-01 met the primary efficacy endpoints with a statistically significant improvement in mean BCVA, measured by Early Treatment Diabetic Retinopathy Study (ETDRS) score from baseline to week 6 versus vehicle (7.2 letters vs. 3.1 letters; P = .007). This effect was sustained to week 12 with statistical significance (7.6 letters vs. 3.7 letters; P = .016).

Moreover, the findings suggest a higher percentage of patients in the OCS-01 group achieved a ≥15-letter improvement in BCVA from baseline at Week 6 versus vehicle (25.3% vs. 9.8%; P = .015), which was additionally sustained to week 12 (27.4% vs. 7.5%; P = .009). Data on retinal thickness showed a significant decrease in CST at week 6 versus baseline in the OCS-01 treatment arm (-63.6 µm vs. +5.5 µm; P <.0001), which persisted to Week 12 (-61.6 µm vs. -16.0 µm; P = .004).

The topical agent was considered well-tolerated, and no unexpected adverse events were observed. Based on the 3-month findings, the release suggests OCS-01 has met both clinical efficacy endpoints (mean BCVA change; proportion of patients with 3 line gain) required for regulatory approval if met at 12-month treatment duration.

“I am pleased and very encouraged that in Stage 1 of this trial, OCS-01 has met both the primary and secondary endpoints in a robust and statistically significant manner,” Riad Sherif, MD, CEO of Oculis, said in the statement. “A topical agent has never demonstrated a positive result in DME. Now, OCS-01 has been validated in 2 different studies with consistent and repeated positive results.”

The release noted the company will prioritize the advancement to stage 2 in the phase 3 DIAMOND trial. Stage 2 of the DIAMOND will include 2 global trials, with each enrolling approximately 350 - 450 patients, and is expected to begin in the second half of 2023.

References

1. Oculis announces positive top line results from Diamond Stage 1 phase 3 trial in diabetic macular edema with OCS-01 eye drops. Oculis. May 22, 2023. Accessed May 22, 2023. https://investors.oculis.com/news-releases/news-release-details/oculis-announces-positive-top-line-results-diamond-stage-1-phase.