ReGenTree LLC, a US joint venture company between GtreeBNT and RegeneRx announced results of additional analysis of the phase 3 clinical trial ARISE-3, using RGN-259 for the treatment of dry eye syndrome.  The company also pooled data from all three phase 3 clinical trials for dry eye.

In ARISE-3, a symptom of efficacy was seen in the improvement of ocular grittiness, one of the pre-specified secondary endpoints.  The statistically significant difference was seen at one and two weeks after treatment, and post-exposure to an exacerbated environment after two weeks of treatment with RGN-259 compared to placebo (p = 0.0094, 0.0384, and 0.0079, respectively).  Also, statistically significant differences were seen with improvement in ocular discomfort during the first week of treatment (as noted in the subject diary) and with several items of the Ocular Surface Disease Index (OSDI) at Day 15, which were other prespecified secondary symptom endpoints.

In addition, through post-hoc analysis, statistically significant differences were seen in the central corneal fluorescein staining score for sign efficacy at 2 weeks after treatment in a subpopulation of ARISE-3 and in the pooled population of three trials of ARISE-1, -2, and -3 comprised with corneal sum fluorescein staining score at the baseline (ARISE-3, p = 0.0352; Pooled data of three trials, p = 0.0074) and in a subpopulation of ARISE-2 and in the pooled population of three trials comprised with inferior corneal fluorescein staining score and Schirmer's test score at the baseline (ARISE-2, p = 0.0057; Pooled data of three trials, p = 0.0196).  In terms of safety and tolerance, it was confirmed that RGN-259 continued to demonstrate safety in the treatment of dry eye syndrome consistent with previous clinical trials.

Dry eye syndrome is a multifactorial disease with various underlying causes.  For treatment, it is important not only to treat the inflammation but also to repair the damaged eye surface and restore tear film homeostasis.  These multiple pathologies highlight the importance of drugs with a variety of therapeutic mechanisms along with anti-inflammatory therapeutics.  Last year, the US FDA released draft guidance for developing drugs for the treatment of dry eye syndrome.  

ReGenTree is developing RGN-259, which contains thymosin b4 (Tß4) as a drug substance for ophthalmic indications.  RGN-259 regulates inflammation, wound healing, cell protection, cell migration, and apoptosis.  The ARISE-3 trial enrolled 700 patients in 20 clinical trial sites nationwide.

A company official said, "We think that the safety and efficacies of RGN-259 are demonstrated in both signs and symptoms for the treatment of dry eye based on ARISE-3 and the pooled data of all three phase 3 trials."

Based on the recent reclassification of RGN-259 to a Biologics License Application (BLA) and the draft guidance for dry eye from the US FDA, the company has started discussions with regulatory consulting firms to explore the prospects of a pre-BLA meeting with the US FDA using these comprehensive data from all three phase 3 trials.  The company will proceed with a request for a pre-BLA meeting and future development steps will depend on the discussion results.  If RGN-259 is approved, the company anticipates that RGN-259 will have market exclusivity for 12 years as a BLA product.