Kolon TissueGene’s Cell and Gene Therapy TG-C Fails to Meet Primary Endpoints in Phase 3 Knee Osteoarthritis Trial

July 26, 2026

Fierce Biotech USA

Overview

Kolon TissueGene’s cell and gene therapy TG-C failed to achieve its co-primary endpoints in the Phase 3 ACTiVION-II trial for knee osteoarthritis, showing no significant improvement in pain or function compared to placebo at 12 months. While no new safety concerns emerged, this negative outcome prevents TG-C from reaching its goal as a disease-modifying osteoarthritis drug (DMOAD) and will significantly impact its future development strategy. The company has a history of trial delays due to manufacturing issues.

In Depth

Key Findings

Kolon TissueGene announced that its cell and gene therapy, TG-C, failed to meet its co-primary endpoints in the Phase 3 ACTiVION-II clinical trial for knee osteoarthritis. The therapy did not demonstrate superiority over placebo in improving pain or function at the 12-month mark, delivering a significant setback to the product’s regulatory pathway and commercialization prospects.

Technical and Clinical Details

TG-C is an allogeneic cell and gene therapy combining human allogeneic chondrocytes with cells engineered to express transforming growth factor-beta 1 (TGF-β1). The ACTiVION-II trial evaluated the efficacy and safety of a single intra-articular injection of TG-C in patients with moderate to severe knee osteoarthritis. Regrettably, the primary endpoints—improvement in Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain and function scores from baseline compared to placebo—were not statistically significant. On the safety front, the incidence, severity, and patterns of adverse events were comparable between the treatment and placebo groups, with no new safety signals identified. While this suggests a potentially safe profile for the treatment, the lack of efficacy remains the critical issue.

Background & Context

Osteoarthritis affects hundreds of millions worldwide, yet there remains a profound unmet need for effective disease-modifying osteoarthritis drugs (DMOADs). TG-C was a high-profile candidate aiming for DMOAD approval, and its failure underscores the immense challenges in developing such treatments for this large market. Kolon TissueGene has faced numerous hurdles previously, including a clinical hold due to manufacturing issues with TG-C, further highlighting the critical importance of robust quality control and manufacturing stability in regenerative medicine products. This outcome reflects the inherent complexities and high attrition rates in late-stage clinical development for novel therapies.

Strategic Significance & Outlook

The failure to meet primary endpoints renders the commercialization path for Kolon TissueGene’s TG-C highly uncertain. The company will now need to await results from another ongoing Phase 3 trial (ACTiVION-I) and will likely face extensive discussions with regulatory authorities, potentially requiring additional data submission or new trials. While the clinical need for DMOADs in knee osteoarthritis remains high, this result demonstrates that even promising regenerative medicine approaches confront substantial hurdles. The broader regenerative medicine industry may need to re-evaluate strategies for osteoarthritis, learning from this experience to refine future development pipelines and clinical trial designs.

Source: https://www.cgtlive.com/view/cell-therapy-tg-c-misses-primary-endpoints-phase-3-knee-osteoarthritis-trial

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