Kolon TissueGene releases first Phase 3 trial results for TG-C, falls short of statistical significance

Kolon TissueGene has released the first top-line results from its US Phase 3 clinical trial of TG-C, a cell and gene therapy for osteoarthritis. The trial showed the drug reduced pain and improved joint function, but the results did not meet statistical significance after the placebo group posted a far stronger response than anticipated.

According to Kolon TissueGene on Tuesday, the trial's co-primary endpoints at the 12-month mark — the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and the Visual Analogue Scale (VAS) — showed a VAS pain score of -38.6 and a WOMAC score of -26.34 in the TG-C group. Those figures were comparable to, or exceeded, treatment-group data from the company's earlier US Phase 2 trial and South Korean Phase 3 trial.

However, the trial failed to show a statistically significant difference against the placebo group. The placebo group recorded a VAS pain score of -39.1 and a WOMAC score of -27.57 at 12 months. The company said the placebo group's improvement far exceeded the assumptions built into the trial design, preventing the results from reaching the predefined threshold for statistical significance between the two groups.

Elevated placebo responses have been documented in clinical trials for pain conditions such as osteoarthritis, particularly in studies involving direct intra-articular injections. Kolon TissueGene identified the unexpectedly strong placebo response as the key factor behind the outcome and said it is conducting a detailed analysis from multiple angles, including subgroup analysis, to determine the underlying causes.

No safety concerns were identified. The trial also showed a meaningful difference in the rate of total knee replacement surgery, a procedure typically required when osteoarthritis worsens significantly. Only 0.6 percent of patients in the TG-C group (2 out of 310) underwent the procedure, compared with 5.3 percent in the placebo group (8 out of 151) — a rate approximately 8.8 times lower.

On the basis of these results, Kolon TissueGene said it has decided to bring on Andy Weymann, an orthopedic surgeon, as its new chief medical officer to lead further analysis and broaden the drug's development strategy. Weymann previously served as CMO at global healthcare company Smith+Nephew for 14 years.

In addition, Kolon TissueGene is preparing to release top-line results from a second US Phase 3 trial of TG-C in October. Although the two trials followed the same protocol, they were conducted independently at different clinical sites, with different investigators and patient populations.

"In this first trial, we believe the larger-than-expected placebo response had a significant impact on how the results should be interpreted, and we are conducting a thorough, multi-angle analysis of various factors, including differences in response across sites," said Noh Moon-jong, chief executive of Kolon TissueGene. He added, "The second trial, whose results will be announced in October, is not a simple repeat of the first — it is an independent observation conducted in a different environment, and we are watching its outcome very carefully."