Oculis announces positive top line results from Phase 3 trial of OCS-01 drops for diabetic macular edema

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Oculic Holding AG today announced positive top line results from Stage 1 of its Phase 3 DIAMOND trial of OCS-01 eye drops in diabetic macular edema (DME).

According to the company DME is the leading cause of visual loss and legal blindness in patients with diabetes, affecting around 37 million people worldwide, with a significant number of patients left untreated due to a lack of convenient treatment options.

Riad Sherif, MD, CEO of Oculis, pointed out during a conference call that company officials were pleased the retinal eye drop OCS-01 met primary and secondary endpoints in a robust and statistically significant manner.

“A topical agent has never demonstrated a positive result in DME,” Sherif said. “Now, OCS-01 has been validated in two different studies with consistent and repeated positive results. We remain focused on advancing with high priority the DIAMOND Phase 3 trial to Stage 2. This important milestone has the potential to bring us one step closer to providing the first treatment in the form of eye drops to patients with DME which is a devastating and blinding disease.”

With current results consistent with previous trials, Sherif noted the company is now moving on to two Phase 3 trials in the second half of the year with 350 to 450 participant in the trials.

DIAMOND is a Phase 3, two-stage, double-masked, randomized, multi-center trial to assess the efficacy and safety of OCS-01 eye drops in DME patients. The primary objective of Stage 1 was to select the optimal dosing regimen. Stage 1 was conducted in 39 sites across the USA and Europe with 148 patients randomized 2:1 to receive OCS-01 (n = 100) or vehicle (n = 48) six times daily for a six-week loading phase and then three times daily for a subsequent six-week maintenance phase.

Sherif noted that stage 2 is the upcoming trial, with the difference being the timing of the endpoint, which is the same as stage 1.

The company noted in its news release target 1 met the primary efficacy endpoint with a statistically significant improvement in mean BCVA “Early Treatment Diabetic Retinopathy Study” chart (BCVA ETDRS) score from baseline to Week 6 versus (vs) vehicle (OCS-01: 7.2 letters vs vehicle: 3.1 letters, p = 0.007) demonstrating strong visual gain in the treatment arm. The effect was sustained to Week 12 with statistical significance (OCS-01: 7.6 letters vs vehicle 3.7 letters, p = 0.016). Furthermore, there was a higher percentage of patients in the OCS-01 group who achieved ≥15-letter improvement in BCVA from baseline vs vehicle at Week 6 (OCS-01: 25.3% vs vehicle: 9.8%, p=0.015), which was sustained to Week 12 (OCS-01: 27.4% vs vehicle 7.5%, p = 0.009).

OCS-01, in this 3-month trial, has met both clinical efficacy endpoints (main BCVA change, proportion of patients with 3 lines gain) that are required for regulatory approval, if met at 12 months treatment duration.

An effect on retinal thickness was also observed with a statistically significant decrease in Central Subfield Thickness (CST) at Week 6 versus baseline in the OCS-01 treatment arm (OCS-01: -63.6 µm vs vehicle: +5.5 µm, p<0.0001). The decrease in retinal thickness persisted to Week 12 (-61.6 µm vs -16.0 µm, p=0.004).

OCS-01 was well-tolerated with no unexpected adverse events observed.

The OCS-01 development program will continue as planned with Stage 2 which includes two global trials, each enrolling approximately 350-450 patients. Oculis expects to begin Stage 2 of the DIAMOND trial in the second half of this year.

Arshad M. Khanani, MD, MA, director of clinical research at Sierra Eye Associates and Clinical Associate Professor at University of Nevada, Reno School of Medicine, Reno, Nevada and Co-Principal Investigator for the DIAMOND trial, served as a co-principal investigator and was pleased with the trial and its results.

“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,” he said. “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. I am looking forward to enrolling patients in Stage 2 of this trial.”

David S. Boyer, MD, an adjunct clinical professor of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles and Co-Principal Investigator for the DIAMOND trial, highlighted some of the details of the trial, pointing out the mechanism of DME involves both increased permeability and inflammation.

“Current anti-VEGFs are effective as anti-permeability agents but have no effect on inflammation,” Boywe ais. “Therefore, a significant proportion of patients are sub-optimally treated with anti-VEGFs alone.”

Boyer added that if approved, OCS-01 has the potential to complement current treatment and address recalcitrant patients.

“Furthermore, since it is a topical agent, it has also the potential to be a first line treatment in DME, if approved,” he said. “In short, I believe the impact of OCS-01 in DME could be a true game-changer.”

Boyer added that if approved, OCS-01 has the potential to complement current treatment and address recalcitrant patients.

“Furthermore, since it is a topical agent, it has also the potential to be a first line treatment in DME, if approved,” he said. “In short, I believe the impact of OCS-01 in DME could be a true game-changer.”

Boyer added that he was confident the drug effect is real.

“The OCT here improved,” he said. “The finding of the visual improvement and the OCT improvement makes me confident this is a real effect.”

“For the first time in our field, we can have a topical therapeutic for DME,” Khanani said.

About OCS-01 eye drops

Oculis noted by leveraging itsOptireach technology, OCS-01 is a novel, high concentration (15 mg/ml), topical formulation of dexamethasone. It is developed to reach the retina via an eye drop, a route of administration for DME that is in contrast with currently available therapies, all requiring the use of more invasive treatments such as ocular implants or intravitreal injections to deliver the medication to the retina.

Sherif noted the therapeutic has been proven effective as an implant, noting the newness is its use as an eye drop.

The company noted its Optireachsolubilizing formulation technology addresses the main limitations of conventional eye drops by improving the solubility of lipophilic drugs, increasing the residence time on the eye surface and thereby, enabling the drug passage from the eye surface to the posterior segment of the eye.

During the 12-week treatment period of the trial, Sherif noted 22% of patients showed any IOP increase at all during the study. He pointed out that IOP increases were consistent with the literature.

“We had only one patient who had an increase higher than 35 in the entire study, and 11 patients were treated with IOP lowering medications,” he said.

About Diabetic Macular Edema (DME)

DME is the leading cause of visual loss and legal blindness in patients with diabetes. Currently, it is estimated to affect around 37 million people worldwide and, with the rise of diabetes, the prevalence is expected to increase to 53 million by 2040^1,2. DME is an irreversible and progressive complication of diabetic retinopathy and is related to consistently high blood sugar levels that damage nerves and blood vessels in the macula, the area of the retina responsible for sharp vision. DME occurs when blood vessels in the retina swell, and then leak, leading to a fluid build-up (edema) into the retina. There remains a significant need for safer, more effective, longer lasting, and less burdensome treatments for DME patients.

References:

1. Yau et al. Global Prevalence and Major Risk Factors of Diabetic Retinopathy, Diabetes Care 2012 Mar; 35(3): 556-564

2. International Diabetes Federation – diabetesatlas.org Estimated diabetes prevalence worldwide in 2021: 537m, reaching 783m in 2045