Less than a week after enrolling the first patient in a phase IIb/III test of its therapeutic eye drops for dry eye syndrome, Regenerx Biopharmaceuticals Inc. has enrolled the first participant in a phase III study of the therapy, RGN-259, for the potential treatment of neurotrophic keratopathy (NK), a rare degenerative disease of the outer layer of the eye often caused by diabetes and herpes zoster virus, among other pathologies.

Both trials are sponsored by Regentree LLC, a joint venture between Regenerx and G-treebnt Co. Ltd., which will pay 100 percent of the development and commercialization costs for RGN-259. Completion of each trial, both conducted by the contract research organization Ora Inc., is expected in early 2016.

With fewer than 200,000 cases of NK in the U.S., the FDA granted RGN-259 orphan status from the indication at the end of 2013. Success in the arena, though relatively small, could prove a valuable point of differentiation for Regenerx, which has an initial 49 percent of Regentree and G-treebnt, which owns the remainder, as they seek to stake a claim in the vastly larger dry eye therapy market, which is currently dominated by Allergan Inc.'s Restasis (0.05 percent cyclosporine solution). Restasis logged about $1.1 billion in global revenue in 2014.

The NK trial is a double-masked, placebo-controlled study being conducted at eight sites, which include major U.S. medical centers. It will enroll about 46 patients with chronic stage 2 and stage 3 NK, and is expected to be completed by the end of the first quarter of 2016, or shortly thereafter.

The study's primary endpoint is complete corneal healing in patients using RGN-259 as compared to those using placebo. Patients will use the eye drops five times daily for 28 days and will be assessed periodically during treatment, upon completion of treatment, and at one week and two weeks after treatment. There will be numerous secondary endpoints that will also be evaluated pursuant to the trial protocol.

Regenerx announced the start of enrollment for the 350-patient dry eye trial on Sept. 16. It's a double-masked, placebo-controlled trial being conducted at four sites. The co-primary endpoints are assessments of total corneal staining and reduction of ocular discomfort in treated patients vs. those using placebo. Patients will use the eye drops four times daily for 28 days and be assessed periodically throughout the trial and at completion of treatment. The trial is expected to be completed by the end of the first quarter of 2016.

Synthetic thymosin beta 4, the active ingredient in RGN-259, is a first-in-class, naturally occurring molecule that has been the subject of numerous published animal studies in the fields of ophthalmology, dermatology, cardiology and central nervous system disorders, among others. It's thought to reduce inflammation by down-regulating inflammatory cytokines while also inhibiting the activation of nuclear factor kappa B in corneal epithelial cells. It has also been found to promote epithelial cell migration and wound repair in the eye; protect cells from cytotoxicity; promote angiogenesis (though not in the eye); promote stem cell recruitment and differentiation; and reduce apoptosis, all of which are believed to be important for effective treatment of dry eye syndrome. Numerous earlier studies have also shown the drug to be safe and well tolerated.

In addition to its U.S.-based trials, Regenerx is also pursuing dry eye syndrome in China, where it established a partnership with Hong Kong-based Lee's Pharmaceuticals Ltd. last year to tackle the growing incidence of the problem due to pollution. Lee's is currently awaiting approval from the CFDA to start a phase IIb study in the indication. Meanwhile, G-treebnt has secured approval from Korean regulators to start a phase IIb/III study there, but it holding off until the U.S. studies get off the ground. (See BioWorld Today, June 25, 2014.)

J.J. Finkelstein, Regenerx's president and CEO, told BioWorld Today that he's very pleased with the company's current position. "We've got these three territories and four clinical trials, two of which have started now, where we have no financial exposure and a lot of upside benefit. We're excited about that. We think we've really positioned ourselves in a great spot and we're looking forward to getting results now," he said.

Regenerx has created three formulations of the thymosin beta-4-based drug, including the sterile eye drop for RGN-259, a dermal gel that it's advancing as RGN-137, and an injectable solution meant to address various tissue sites after trauma or disorder, called RGN-352.

Finding a partner for RGN-352 is next on the company's agenda, said Finkelstein. That program would likely focus immediate use of the therapy following a ST-elevation myocardial infarction with the goal of preventing the damage caused by both the ischemic event and later reperfusion.