RegeneRx Biopharmaceuticals, a clinical-stage drug development company focused on tissue protection, repair and regeneration, has announced positive results from its second clinical trial evaluating RGN-259 for the treatment of dry eye, sponsored by ReGenTree, its U.S. joint venture with GtreeBNT in Korea.
The 317-patient phase II/III trial demonstrated statistically significant improvements in both signs and symptoms of dry eye with 0.05% and 0.1% RGN-259 compared to placebo in a dose dependent manner during a 28-day dosing period. While the primary outcome measures were not met, several key related pre-specified endpoints and subgroups of patients with more severe dry eye showed statistically significant treatment effects. These results confirm the findings from the previous phase II trial providing clear direction for the clinical regulatory pathway and remaining registration trials for RGN-259.
RGN-259 was evaluated using the Controlled Adverse Environment (CAE) Model developed by Ora, the product development firm managing the program. The CAE was utilized to screen and enroll an enriched patient population and measure a patient's ability to withstand an acute adverse environmental challenge of the ocular surface.
On the final day of dosing (Day 28), patients receiving 0.1% RGN-259 had a statistically significant reduction in ocular discomfort during CAE exposure when compared to placebo (Intent-to-Treat Population (ITT), p=0.043). Importantly, this result was also observed in the previous phase II trial in patients treated with 0.1% RGN-259 (ITT, p=0.024), thereby demonstrating a symptom endpoint in two independent trials. A statistically significant ocular discomfort improvement after CAE exposure on day 28 was also observed in the 0.05% and 0.1% RGN-259 treatment arms when compared to placebo (ITT, p=0.0366 and p=0.0072, respectively) indicating a dose dependent response.
Efficacy in an environmental setting was also demonstrated in more symptomatic patients at baseline, with statistically significant improvements in ocular discomfort observed at day 28 prior to CAE in patients receiving 0.05% and 0.1% RGN-259 compared to placebo (p=0.022 and p=0.006, respectively). These data suggest that RGN-259 has a fast-acting treatment effect on a dry eye symptom during exposure to an adverse environment as well as in the natural environment after 28 days of dosing.
RGN-259 also improved a common objective endpoint ocular surface staining after 28 days of dosing in patients with compromised tear film break-up time at baseline. In this population, patients receiving 0.1% RGN-259 had a statistically significant reduction in corneal fluorescein staining prior to entering the CAE on day 28 when compared to placebo (p=0.034). The same result was observed in the previous phase II trial for patients treated with 0.1% RGN-259, although it was not statistically significant in the smaller sample size of this previous phase II trial.
Additionally, a change from baseline analysis (day 28 minus day zero) demonstrated a statistically significant improvement in inferior corneal staining for the 0.1% RGN-259 treatment arm when compared to placebo (p=0.003). This finding was also observed at day 14 compared to placebo (p=0.035). These data suggest that RGN-259 has a fast-acting treatment effect on a dry eye sign after 14 and 28 days of dosing.
There were no significant drug-related adverse or serious adverse events and RGN-259 was well-tolerated and comfortable for the patients with no irritation upon instillation.
"We are moving forward as rapidly as possible with our program to meet our target timeline for NDA approval in 2018," said Won S. Yang, CEO of ReGenTree.
ReGenTree intends to meet with the FDA this summer to provide full results of the trial and its plan to conduct a confirmatory phase III study to start by the 4th quarter of 2016.