TG-C, the osteoarthritis treatment candidate developed by Kolon TissueGene—formerly known in Korea as Invossa—failed to meet its primary endpoint in the first of two U.S. Phase 3 clinical trials.
The company described the outcome as “not a failure, but a partial success,” and is now pinning its hopes on results from a second Phase 3 trial scheduled for October. However, industry observers say the latest setback has heightened uncertainty surrounding the Kolon Group’s biotech business, which it has positioned as a key future growth engine.
According to industry sources on July 22 (EST), TG-C was previously commercialized in South Korea under the brand name Invossa.
Invossa is a gene therapy injection for osteoarthritis consisting of two components: one containing human cartilage cells and another containing genetically modified cells engineered to produce a cartilage growth factor.
The therapy became Korea’s first approved gene therapy in 2017. However, its marketing authorization was later revoked after regulators discovered that the second component, which had been described in regulatory filings as cartilage-derived cells, actually contained kidney-derived GP2-293 cells.
The U.S. Food and Drug Administration (FDA) subsequently placed the ongoing U.S. Phase 3 trial of TG-C on clinical hold. Following discussions with regulators, the trial resumed in December 2021, and the first set of results has now been released.
Although TG-C demonstrated improvements in both pain, measured by the Visual Analog Scale (VAS), and joint function, measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the placebo group also showed unexpectedly strong improvement, preventing the study from achieving statistical significance.
As a result, the first pivotal trial failed to generate the primary efficacy data needed to support an FDA marketing application, making delays to the company’s original U.S. approval timeline increasingly likely.
More Than the Placebo Effect, Reproducibility Is the Key Question
Kolon TissueGene attributes the disappointing outcome primarily to an unexpectedly strong placebo response.
While placebo effects are common in osteoarthritis trials, the company noted that they typically decline after three to six months. In this study, however, placebo responses remained elevated throughout the 24-month evaluation period.
The company has begun analyzing the raw clinical data—including differences among study sites, patient populations, and assessment methods—to determine the cause by the end of this year.
Industry experts, however, argue that the more important issue is not the placebo response itself, but whether the second Phase 3 trial produces the same outcome.
If the second study also fails to demonstrate efficacy, the company’s U.S. regulatory strategy for TG-C would likely require a fundamental overhaul.
Kolon TissueGene plans to review the results of the second U.S. Phase 3 trial (TGC12301), expected in October, before discussing its regulatory strategy with the FDA.
One positive factor is that the FDA has recently indicated it may consider approving certain therapies based on a single robust pivotal study. Whether that approach could apply to TG-C, however, remains entirely at the agency’s discretion.
The latest results also represent a setback for the broader Kolon Group.
The conglomerate has positioned TG-C as the flagship asset of its biotech business and last year recruited veteran pharmaceutical executive Jeon Seung-ho as co-CEO to prepare for commercialization following potential U.S. approval.
With the first pivotal trial falling short, commercialization is likely to be delayed, potentially extending the timeline for recovering the group’s investment.
Still, many industry observers caution against drawing definitive conclusions at this stage.
A second independent U.S. Phase 3 study using the same trial design is still underway, meaning the outlook could change significantly depending on the October results.
Moreover, the first trial did not produce entirely negative findings.
The therapy demonstrated a safety profile consistent with previous studies, with no new safety concerns identified.
Notably, the rate of total knee arthroplasty (TKA) was substantially lower in the TG-C group than in the placebo group, with procedures performed in 2 of 310 patients (0.6%) receiving TG-C compared with 8 of 151 patients (5.3%) in the placebo arm.
Although TKA incidence was not a primary endpoint and therefore cannot serve as regulatory evidence for approval, the finding may suggest that TG-C has the potential to slow disease progression.
Ultimately, if the second Phase 3 trial demonstrates statistically significant efficacy, discussions with the FDA could resume and the possibility of U.S. approval may be revived.
Conversely, if the second study yields similar results, the company may need to conduct additional clinical trials or substantially revise its development strategy.
In effect, the future of both Kolon TissueGene and the Kolon Group’s broader biotech ambitions now hinges on the outcome of the second U.S. Phase 3 trial, expected in October.