[Edaily Reporter KIM SAE-MI ] Kolon TissueGene, Inc.(950160)’s Phase 3 clinical trial press conference for TG-C, which emphasized “half a success,” once again exposed flaws in the company’s data management and internal verification systems as figures in its regulatory filings, press releases, and presentation materials were found to differ.

Called

a “Half Success”… Neither Primary nor Secondary Endpoints Reached Statistical Significance

Kolon TissueGene, Inc. held a press conference to announce the results of the U.S. Phase 3 clinical trial for TG-C at 10:00 a.m. on the 21st at the KOLON CORPORATION One & Only Tower in Gangseo-gu, Seoul.

At the press conference, Jeon Seung-ho, Co-CEO of Kolon TissueGene, Inc., opened his remarks by saying, “I absolutely do not consider this clinical trial a failure. While it is not a success, it is not a failure either—I view it as a partial success,” adding, “I hope you will see this as a growing pain.”

Co-CEO Jeon explained, “Within the TG-C treatment group itself, the efficacy was equivalent to or exceeded that of previous clinical trials,” adding, “Although we were unable to demonstrate a difference compared to the placebo group, we will identify the cause and incorporate the findings into future development.” He continued, “We plan to conduct a detailed and comprehensive analysis, including the raw data, to determine why these results occurred,” emphasizing that “this effort is not only to identify the cause but also to prepare for future regulatory approval and subsequent procedures.”

Previously, Kolon TissueGene, Inc. announced the results of TG-C’s U.S. Phase 3 clinical trial (Study 15302) at 5:55 p.m. on the 20th. Neither the 12-month VAS pain score nor the WOMAC total score—both of which were co-primary endpoints—achieved statistical significance compared to the placebo.

The change in VAS scores was -38.7 for the TG-C group and -39.2 for the placebo group, with the placebo group showing a 0.5-point greater improvement. The p-value was 0.8322. For the WOMAC total score, the TG-C group recorded -27.61 and the placebo group -26.54; while the TG-C group showed a 1.07-point greater improvement, the p-value was only 0.5701. Both measures were significantly different from the general statistical significance threshold of a p-value of 0.05.

No statistically significant differences compared to the placebo were observed in the four secondary endpoints disclosed by the company during the briefing. According to the briefing materials, WORMS cartilage damage at the 12-month mark was 18.4% in both the TG-C group and the placebo group, with a p-value of 0.9868. The SF-12v2 PCS (Physical Health Subscale) was 6.98 vs. 7.66 (p=0.4062); the 24-month WOMAC total score was -26.79 vs. -26.81 (p=0.9905); and the 12-month HAQ-DI was -0.22 versus -0.24 (p=0.7432). This means that none of the two co-primary endpoints or the four secondary endpoints disclosed by the company demonstrated efficacy compared to the placebo.

Instead, the company emphasized that the incidence of total knee arthroplasty (TKA) was 0.6% (2 out of 310) in the TG-C group and 5.3% (8 out of 151) in the placebo group. The nominal p-value from the Fisher exact test was approximately 0.0027.

However, the company’s press release also explicitly states that, since the joint primary endpoints were not met, the TKA results must be interpreted at a “descriptive level” under the pre-defined hierarchical testing framework. The total number of events was only 10, and the WORMS—a structural endpoint—showed no difference between the two groups. This is why it is difficult to conclude, based solely on the TKA incidence rate, that TG-C suppressed disease progression or delayed surgery.

Discrepancies in Numbers Across Public Disclosures, Press Releases, and Briefings

Confusion also persisted during the data disclosure process. The figures for each indicator presented at the press briefing that day did not match those in the public disclosure, and different numbers were used even within the presentation materials themselves.

The summary table from the briefing listed the 12-month change in WOMAC scores as -27.57 for the TG-C group and -26.34 for the placebo group. In contrast, the press release distributed the previous day and the trend graph presented during the briefing showed the values for the treatment and placebo groups reversed: TG-C group -26.34 and placebo group -27.57. These values also differ from those stated in the regulatory filing: TG-C group -27.61 and placebo group -26.54.

For VAS, the press release and the briefing summary table both listed the TG-C group as -38.6 and the placebo group as -39.1, but these did not match the figures in the regulatory filing of -38.7 and -39.2. The p-values were also shown differently: 0.8322 in the regulatory filing and 0.8494 in the briefing materials.

In response, the company explained, “Errors occurred because the figures fluctuated during repeated first- and second-round revisions as the data was transmitted from the U.S.,” adding that “the figures in the regulatory filing are the final, confirmed data and the officially valid standards.”

Following its explanation the previous day that the error in the press release was due to a mistake by the person in charge of drafting it, the company repeated the use of figures differing from the regulatory filing and inconsistent notation within the materials during the briefing the next day. Given that the errors spanned multiple documents and metrics—making it difficult to dismiss them as mere typos—this raises significant questions about whether the management of topline data, the verification of statistical results, and the approval system for regulatory filings and promotional materials functioned properly.

Root Cause Analysis Has Just Begun… Possibility of Additional Clinical Trials

The company reiterated its explanation that, while the TG-C group showed symptom improvement similar to or greater than that observed in previous clinical trials, an unexpectedly strong placebo response persisted over a long period, preventing the company from demonstrating a significant difference between the groups.

Former Co-CEO Jeon analyzed, “We were in a situation where past results absolutely had to be replicated more strongly this time, but this outcome resulted from the significant variable of the placebo effect.” He also raised the possibility that the use of painkillers, high baseline pain scores, and variations among trial sites or evaluators may have amplified the placebo response.

However, the specific cause has not yet been identified. Dr. Andy Weymann, M.D., who will oversee the root cause analysis, stated, “We will investigate everything from A to Z—from the investigational drug to data reading and analysis,” but added, “The full-scale investigation has not yet begun and is scheduled to start within a few days.” He set a goal of identifying the general cause by the end of this year but noted that it is difficult to guarantee the final investigation will be completed by then.

The remaining hope now lies in the topline results of the second U.S. Phase 3 clinical trial (Study 12301), scheduled for release this October. While the second trial shares the same protocol and design as the first, it differs in terms of trial sites, principal investigators, and patient cohorts. Co-CEO Noh Moon-jong noted, “Since it is a separate, independent trial, we cannot predict the results.”

Even if the second trial is successful, it is difficult to rule out the possibility of pursuing additional clinical trials. Co-CEO Jeon noted, “The FDA recently indicated that it might consider the application if very strong results emerge from even a single clinical trial,” but added, “From a conservative perspective, additional data may be required. This is also why we are seeking to identify the cause.”

Co-CEO Jeon’s remarks are presumed to refer to the draft guidance on demonstrating efficacy that the FDA released last June. The guidance addresses the possibility of meeting efficacy criteria by combining a single appropriate and well-controlled clinical trial with strong confirmatory evidence. However, the FDA explicitly states that if multiple clinical trials are conducted and one trial confirms a lack of efficacy, it may cast doubt on the positive results of other trials.

The company’s position is that if statistical significance is confirmed in the second trial, it will begin consultations with the FDA and conduct additional clinical trials as required by the regulatory authority. Co-CEO Noh stated, “The patient size and number of sites for the additional clinical trial must be discussed with the FDA, so it is difficult to determine at this time,” but added, “Since this is a trial to confirm efficacy at the one-year mark, we are aiming for a duration of about one year. It could be a relatively small-scale trial involving about 100 to 200 patients.”

The originally proposed timeline—a Biologics License Application (BLA) submission in the first quarter of 2027 and commercialization in 2028—is also expected to be delayed. Co-CEO Jeon reiterated, “It appears the timeline will be later than originally planned,” adding, “We will re-establish the schedule after analyzing the causes and receiving the results of the second trial.” Kolon TissueGene, Inc. had set a target of submitting an FDA application in the first quarter of 2027 when it issued convertible bonds worth 122.5 billion won last year.