In a letter to shareholders, RegeneRx provided a pipeline update for investors Monday, outlining plans to potentially move forward with a new asset in light of development delays.
In a letter to shareholders, RegeneRx provided a pipeline update for investors Monday morning, outlining plans to potentially move forward with a new asset in light of development delays.
Maryland-based RegeneRx is primarily focused on diseases of the eye via ReGenTree, a U.S. joint venture with Korea-headquartered HLB Therapeutics (HLBT). HLBT runs RegenTree and funds the ophthalmic clinical development program. Lead asset RGN-259 is being developed to treat DED and neurotrophic keratitis (NK), a degenerative disease of the cornea.
The company noted that the FDA generally requires “both a sign and symptom of dry eye disease (DED) to be improved by a statistically significant margin in a series of well-controlled clinical trials.” These can be corneal staining or burning, stinging or eye grittiness. Depending on which symptom the trial is designed around, different models are used to assess them.
ReGenTree is running three Phase III ARISE clinical trials of the drug for DED in more than 1,600 patients. It evaluated subgroups of DED patients from the studies and pooled the data. The trials failed to meet the pre-specified co-primary endpoints. However, in ARISE-3, the drug did show statistically significant improvements in ocular grittiness compared to placebo, a common dry eye symptom. The company also observed statistically significant differences in central corneal fluorescein staining, a sign of dry eye, in a subpopulation.
A Path Forward for RGN-259
While the asset failed to meet statistical significance in the pre-specified co-primary endpoints, “RGN-259 did demonstrate statistically significant improvements in both signs and symptoms of dry eye disease in various populations and after one and two weeks of treatment when measured across three Phase III clinical trials in over 1,600 patients,” RegeneRx reported. The company additionally confirmed an “excellent safety profile” for RGN-259.
ReGenTree met with the FDA in February to discuss a possible Biologics License Application submission for REGN-259 for DED. The agency stated that the work to date did not meet the pre-specified co-primary endpoints needed for BLA approval.
ReGenTree has since stated plans to apply for Special Protocol Assessment (SPA) with the FDA in October. This program allows a sponsor company to collaborate with FDA specialists to develop an appropriate clinical protocol and data analysis plan. ReGenTree has advised RegeneRx that it plans to run an ARISE-4 trial in 2023 once the SPA is in place.
The companies have also faced challenges with the Phase III NK trial (SEER-1). In the trial, comprised of 18 participants, six of 10 patients receiving the drug achieved complete corneal healing in four weeks. This was compared with one out of eight in the placebo group.
“We believe this strong trend likely would have reached a statistically significant p value of <0.05 had more patients been entered into the trial,” RegeneRx stated in the letter.
While most of ReGenTree’s resources have been focused on DED, plans are now underway to schedule two simultaneous Phase III studies of the drug in NK. RegeneRx stated a target start date of Fall 2022 for both. The trials, dubbed SEER-2 and SEER-3, are each expected to enroll 60 patients. ReGenTree plans to initiate recruitment before the end of this year, according to RegeneRx.
RegeneRx Eyes Progression of RGN-352
Given the delays with RGN-259, RegeneRx reported that it is re-evaluating opportunities to move forward with RGN-352. An injectable formulation of Tß4 for systemic administration, the asset has shown potential against a range of acute systemic inflammatory disorders, the company said. These include systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), sepsis and COVID-19.
Research conducted by RegeneRx and others suggests that Tß4 can decrease scarring and damage caused by cytokine storms caused by COVID-19 and appears to down-regulate and suppress inflammation.
As a result, renewed efforts are underway to “finance Phase II development of RGN-352 either through government grants, partnerships, and/or additional project-specific funding,” the company said. A prior Phase I trial in 80 healthy patients, “provides the foundation we believe is required for initiating a phase 2a proof-of-concept clinical trial for an acute inflammatory indication,” RegeneRx stated.
