[Edaily Reporter KIM SAE-MI ] HLB Therapeutics(115450)’s “RGN-259,” currently under development as a treatment for neurotrophic keratitis (NK), failed to meet the primary endpoint in its U.S. Phase 3 clinical trial. This marks the sixth time that RGN-259 has failed to demonstrate key efficacy in late-stage clinical trials conducted for the indications of dry eye syndrome and neurotrophic keratitis.

HLB Therapeutics announced on the 16th that the topline results from the U.S. Phase 3 clinical trial (SEER-2) of RGN-259, conducted by its U.S. subsidiary ReGenTree, showed that the primary endpoint did not achieve statistical significance.

The company received the topline results for the primary endpoint from the contract research organization (CRO) that conducted the clinical trial on the 13th. The primary endpoint of this trial was the cure rate four weeks after administration, and no statistically significant difference was observed between the RGN-259 treatment group and the placebo group. To date, specific figures—such as the exact cure rates or the p-values—for the RGN-259 treatment group and the placebo group have not been disclosed.

SEER-2 was conducted at a total of 50 institutions, including 41 medical centers in the United States and 9 medical centers in three European countries—Italy, Spain, and Poland. Patient enrollment was completed last July, and after the clinical trial procedures were concluded in August, data analysis has been underway.

Including these latest results, RGN-259 has now failed to demonstrate statistical significance for the primary endpoint in a total of six late-stage clinical trials. Previously, RGN-259 also failed to meet key endpoints in the ARISE-1, ARISE-2, and ARISE-3 trials—conducted as a treatment for dry eye—as well as in the SEER-1 and SEER-3 trials—conducted as a treatment for neurotrophic keratitis. Among these, ARISE-1 is classified as a Phase 2b/3 trial.

Notably, in the SEER-1 trial—whose results were released in 2020—the study was terminated after enrolling only 18 participants out of a target of 46. At that time, the Fisher’s exact test for the primary endpoint yielded a P-value of 0.0656, failing to meet statistical significance. However, the company assessed the result as positive, citing a P-value of 0.04 from the chi-square test.

In the European Phase 3 clinical trial (SEER-3) announced last June, statistical significance was also not achieved for the cure rate four weeks after administration. At the time, the company explained that while a number of patients achieved a cure in the RGN-259 treatment group, a higher-than-expected treatment response was observed in the placebo group.

Subsequently, HLB Therapeutics stated that it would conduct further analysis of the European clinical trial results and take steps to ensure that the same issue would not recur in the U.S. clinical trial. However, since the SEER-2 trial also failed to meet the same primary endpoint, setbacks in RGN-259’s new drug development strategy have become inevitable.

HLB Therapeutics is scheduled to officially receive the full clinical trial data from the CRO within a few weeks. The company plans to comprehensively analyze the detailed results of the primary endpoint, secondary endpoints, and treatment responses by subgroup, and then review the future development strategy.

Ahn Ki-hong, CEO of HLB Therapeutics, stated, “Although we did not achieve statistical significance for the primary endpoint in these topline results, we plan to thoroughly analyze the full clinical data to comprehensively verify the detailed results related to therapeutic efficacy.” He added, “Based on the analysis results, we will carefully review future development directions and plans, and promptly and responsibly implement any necessary follow-up measures.”