Kolon TissueGene announced on July 20 the topline results from the first analysis of its U.S. Phase 3 clinical trial for TG-C, a cell and gene therapy candidate for osteoarthritis.
In the Phase 3 trial, pain relief and improvements in joint function were observed based on the co-primary endpoints at 12 months, WOMAC and VAS. However, the results did not meet statistical significance.
Looking at the data related to pain relief and functional improvement, the TG-C treatment group recorded a VAS pain score of -38.6 and a WOMAC score of -26.34 at 12 months.
The results were observed at levels similar to or exceeding data from the treatment groups in previous U.S. Phase 2 and South Korean Phase 3 trials. However, because these comparisons involve different clinical trials, they cannot be interpreted as direct evidence of efficacy in place of the difference between the treatment and control groups in the current U.S. Phase 3 trial.
The trial did not achieve statistical significance compared with the placebo group. At 12 months, the placebo group recorded a VAS pain score of 39.1 and a WOMAC score of -27.57. The company said the placebo group showed improvements that significantly exceeded the assumptions established during the trial design, preventing the difference between the treatment and placebo groups from reaching the predefined statistical significance threshold.
Kolon TissueGene is focusing on the unexpectedly strong placebo response as one of the key factors that may have influenced the results. The company is currently conducting detailed analyses from multiple perspectives, including subgroup analyses, to examine the scale and underlying causes of the placebo response.
Clinical trials for pain-related conditions such as osteoarthritis have reported relatively high placebo responses, particularly in studies involving intra-articular injections. Kolon TissueGene said it is closely reviewing related factors while considering the possibility that these characteristics may have affected the trial results.
The topline results showed no safety concerns related to TG-C. The proportion of patients requiring total knee replacement surgery due to worsening osteoarthritis was significantly lower in the TG-C treatment group at 0.6%, compared with 5.3% in the placebo group.
Kolon TissueGene plans to define its future development strategy based on a detailed analysis of the trial results. As part of this effort, the company decided to appoint Andy Weimann, an orthopedic surgeon who served as chief medical officer (CMO) at global orthopedic healthcare company Smith+Nephew for 14 years, as its new CMO.
In addition, the company plans to announce topline results from TG-C’s second U.S. Phase 3 clinical trial in October. While both trials were conducted under the same protocol, they were independently carried out with different clinical sites, evaluators and patient populations.
“Based on the first trial announced today, we believe the unexpectedly large placebo response had a significant impact on the interpretation of the results,” said Noh Moon-jong, CEO of Kolon TissueGene. “We are currently conducting a comprehensive analysis of various factors, including the possibility of differences in responses among clinical sites identified through additional analysis.”
Noh added, “The second trial is not simply a repeat of the first trial, but an independent observation conducted in a different environment. We will closely monitor the results to be announced in October.”
Meanwhile, Kolon TissueGene plans to hold a press conference on July 21 to explain the Phase 3 topline results and its future development strategy. CEO Noh and other executives will attend the event to provide a detailed analysis of the clinical results and outline future development plans.