[Edaily Reporter YU JIN-HEE ] “TG-C,” a cell-gene therapy candidate for knee osteoarthritis developed by Kolon TissueGene, Inc.(950160)—better known as Inbosa—failed to meet the primary efficacy endpoint in the topline results of its U.S. Phase 3 clinical trial. The company failed to demonstrate a statistically significant difference compared to the placebo (saline) in key indicators measuring pain reduction and improvements in joint function in patients, raising expectations of a major revision to its U.S. commercialization roadmap and a challenging path ahead in consultations with regulatory authorities.

On the 20th, Kolon TissueGene, Inc. disclosed the topline data from the U.S. Phase 3 clinical trial of TG-C (TG-G 15302 Study) in patients with knee osteoarthritis via the Financial Supervisory Service’s electronic disclosure system.

According to the disclosed efficacy results, TG-C failed to demonstrate statistical significance compared to the placebo for both the VAS (Visual Analogue Scale) pain score and the change in the WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) total score—the co-primary efficacy endpoints—at the 12-month mark.

The mean reduction in VAS scores—which reflect patients’ subjective pain—from baseline was -38.7 in the TG-C group and -39.2 in the placebo group, indicating that the numerical difference between the two groups was virtually negligible. The difference between the two treatment groups was 0.5 points, and the p-value—the metric used to determine statistical significance—was 0.8322, which was well above the significance threshold (less than 0.05).

The WOMAC total score, which comprehensively evaluates joint stiffness, pain, and the ability to perform activities of daily living, also showed almost no difference between the treatment groups. The change from baseline was -27.61 for the TG-C group and -26.54 for the placebo group. The difference between the groups was -1.07 points, and the p-value was 0.5701, failing to statistically demonstrate a clear therapeutic efficacy compared to the placebo.

Safety and tolerability during long-term drug administration were consistent with existing data. This safety evaluation was conducted using a mixed-model repeated measures (MMRM) statistical model to perform a detailed analysis based on data accumulated over the entire 104-week (24-month) period from 531 actual patients who participated in the clinical trial.

The overall incidence of treatment-emergent adverse events (TEAEs) following TG-C administration remained similar between the treatment group (83.9%) and the placebo group (78.1%). The incidence of severe adverse events (TG-C 14.8% vs. placebo 11.9%) and serious adverse events (TG-C 10.3% vs. placebo 8.6%) also showed no significant difference compared to the control group.

Most of the reported adverse events were mild (Grade 1 or 2). No clinically significant new safety concerns or warning signals were identified. In particular, the rate of total knee replacement (TKR)—a procedure involving the complete replacement of the knee joint—was only 0.6% in the TG-C group, compared to 5.3% in the placebo group, indicating that safety metrics were maintained.

This top-line data analysis was conducted meticulously by Kolon TissueGene, Inc.’s in-house specialized data analysis team, without outsourcing to a global contract research organization (CRO). It is the result of a key project that spanned over four years, beginning with the receipt of the Investigational New Drug (IND) application in 2018, followed by the first patient dosing in December 2021, and concluding with the final follow-up in May of this year.

Rather than being disappointed by the lack of efficacy in these Phase 3 clinical trial results, Kolon TissueGene, Inc. plans to combine the data with that from another independent Phase 3 clinical trial (NCT03203330) currently underway in the U.S. to achieve a breakthrough.

Noh Moon-jong, CEO of Kolon TissueGene, Inc., stated, “We believe that a larger-than-expected placebo response in the first trial announced this time had a significant impact on the interpretation of the results,” adding, “We are currently conducting a multi-faceted, detailed analysis of various variables, including the possibility of differences in response by organ identified in the additional analysis.” He added, “Since the second trial is not a simple repetition of the first but an independent study conducted under different conditions, we are closely monitoring the results, which are scheduled to be announced this October.”