Kolon TissueGene says ‘TG-C P3T is not a failure’

Company misses primary endpoints in first Phase 3 VAS·WOMAC trial compared with placebo…due to strong placebo response

TKA rate 0.6 in TG-C group and 5.3% in placebo group… suggest potential disease-modifying effect

FDA filing and commercialization likely delayed… second Phase 3 topline due in October

Kolon TissueGene held a press briefing on the 21st to discuss results from the first US Phase 3 trial of its investigational knee osteoarthritis therapy, TG-C.

"We do not consider these results a clinical failure. Rather, we see them as a halfway success. Please consider it as part of our learning curve."

At a press conference held on the 21st, Seong-Ho Jeon, co-CEO of Kolon TissueGene, explained so regarding the results from the first U.S. Phase 3 trial of TG-C, the company's investigational treatment for knee osteoarthritis. The briefing was held to explain the topline results released the previous day and outline the company's analysis and development plans. Jeon was joined by co-CEO Moon-Jong Noh, Chief Financial Officer Jung-In Kim, and newly appointed Chief Medical Officer Andy Weymann.

On July 20, the company disclosed in a filing that its first US Phase 3 study, TGC-15302, failed to achieve statistical significance versus placebo for either of the co-primary endpoints, the Visual Analog Scale (VAS) for pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). VAS pain scores decreased by an average of 38.7 points from baseline in the TG-C group and 39.2 points in the placebo group, a between-group difference of 0.5 points (p=0.8322). Total WOMAC scores fell by 27.6 points in the TG-C group and 26.5 points in the placebo group, with a between-group difference of -1.1 points (p=0.5701).

Seong-Ho Jeon, co-CEO of Kolon TissueGene

Jeon said, “It is true that TG-C did not demonstrate a statistically significant advantage over placebo, but the treatment itself produced greater symptom improvement than those observed in previous clinical trials. We will spend the coming months investigating the unusually strong placebo response and incorporate the findings into subsequent development and regulatory strategies.

The company also highlighted signals suggesting TG-C may have disease-modifying potential, citing total knee arthroplasty (TKA) rates. Only 2 of the 310 patients in the TG-C group underwent TKA, compared with 8 of 151 patients in the placebo group. The incidence rates were 0.6% and 5.3%, respectively, meaning the placebo group experienced TKA at a rate about 8.8 times higher than the TG-C group, which Jeon explained was a statistically significant difference.

"The ultimate goal of osteoarthritis treatment is to manage pain and function over the long term to avoid or delay total knee arthroplasty as much as possible. While this dataset alone cannot answer every question, we plan to continue following patients for 3, even 5 years or longer to determine whether the difference is sustained. The findings could prove valuable not only in discussions with regulators but also in reimbursement and health economic evaluations following commercialization.”

Moon-Jong Noh, co-CEO of Kolon TissueGene

Co-CEO Moon-Jong Noh emphasized that all key efficacy measures in the TG-C group showed clinically meaningful improvement from baseline. Noh noted, “Analysis of the first completed study among the company's two U.S. Phase III trials demonstrated clinically meaningful improvements across both co-primary endpoints and all four secondary endpoints.

Noh said, “In the earlier US Phase II trial, VAS pain scores improved by approximately 35–39 points and the effect was sustained for two years. In the current Phase III trial, pain scores improved by about 38 points at three months and were maintained through Week 104 (24 months). Symptom improvement observed in the Phase III study can be interpreted as being even greater than those seen in previous trials.”

Noh added, “The placebo effect was unexpectedly strong and persistent, preventing the study from demonstrating a difference between treatment and placebo. Placebo groups in osteoarthritis trials typically show improvements of around 9–14 points in VAS and 9–19 points in WOMAC, with those effects generally fading after three to six months. In this trial, however, the placebo group showed improvements comparable to those in the TG-C group at about 40 points in VAS and 25 points in WOMAC, and were maintained through 24 months.”

"Based on analysis of the pre-specified criteria, we concluded that no efficacy difference could be confirmed between the treatment and placebo groups. However, given these findings, we do not believe the therapeutic effect of TG-C itself should be called into question. Rather, we need to conduct further analysis to understand and manage the unusually strong placebo response."

Because the first US Phase III study failed to meet its co-primary endpoints, the company's previously announced timeline of submitting a Biologics License Application to the U.S. Food and Drug Administration (FDA) in 2027 and launching the product in 2028 will likely be delayed. Jeon said, "Because we were unable to demonstrate a difference from placebo in this trial, the timeline will likely be delayed beyond our original expectation. We will establish a revised development timeline after completing a thorough analysis of the underlying causes."

First, the company plans to comprehensively analyze patient- and site-level data from TGC-15302, as well as the use of concomitant analgesics, to determine the cause of the unusually strong placebo response. The new CMO Weymann will lead the analysis, and the company will integrate the final clinical study report, which is expected in Q4, with topline results from the second Phase III study, TGC-12301, scheduled for release in October, to determine its next development strategy. Although the second study has the same design, it is an independent trial involving different patients, investigators, and clinical sites, making its outcome difficult to predict.

The company also plans to discuss regulatory pathways and any additional requirements with the FDA based on the supplementary analyses from the first study and data from the second Phase III trial. Jeon emphasized, "We will establish a clear path forward once a thorough root-cause analysis is complete. Development may take longer than expected, but our commitment to developing TG-C remains unchanged."