[Edaily Reporter Kim Jinsoo ] As Medipost begins full-scale Phase 3 clinical trials in the U.S. for “Cartistem,” a stem cell therapy for knee osteoarthritis, attention is focusing on its potential for success. Despite the clinical challenges faced by Kolon TissueGene’s “TG-C,” analysts believe Cartistem has increased its chances of clinical success by differentiating its trial design based on prior clinical data, patient selection tailored to the treatment’s characteristics, and a long-term evaluation plan.

According to Medipost on the 9th, the U.S. Phase 3 trial for Cartistem is proceeding with a plan to enroll a total of 300 patients across approximately 70 clinical sites in the U.S. and Canada. The first patient received treatment and dosing in July, and the trial is gaining momentum. Cartistem consists of allogeneic mesenchymal stem cells derived from umbilical cord blood; it is applied to damaged cartilage areas with the goal of regenerating cartilage and thereby improving pain and function.

MediPost is conducting the U.S. Phase 3 trial as a single study in consultation with the U.S. Food and Drug Administration (FDA). Compared to the original plan, which envisaged two separate trials, this reduces the overall patient enrollment burden by about half and allows the company to accelerate development by minimizing patient recruitment and cost burdens.

A Medipost official stated, “We plan to conduct patient enrollment and administration by the end of next year, followed by a 24-month follow-up period. The actual completion date may vary slightly depending on the timing of patient enrollment and administration.”

Differences from the TG-C clinical trial:

Both Cartistem and TG-C’s U.S. Phase 3 trials share the common feature of using the Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) as co-primary endpoints. However, they differ in the timing of endpoint measurements: TG-C measures at 12 months post-administration, while Cartistem measures at 24 months.

First, the 24-month evaluation point required by the FDA for Medipost’s Cartistem is more advantageous for verifying the long-term efficacy of cartilage regeneration therapy. This is because, while temporary pain relief may occur following surgery or treatment administration when assessing the efficacy of osteoarthritis therapies, confirming efficacy up to 24 months allows for the identification of a clear difference from the control group. In other words, the study design focuses on the long-term improvement in pain and function over a period of 24 months or more, rather than short-term changes in symptoms.

Since most osteoarthritis treatments use subjective indicators, such as pain, as evaluation variables, they are known to be susceptible to a significant placebo effect. Therefore, given that the placebo effect loses its influence as the period following treatment or administration lengthens, 24-month data is more advantageous for proving efficacy than 12-month data.

A Medipost official stated, “There is a difference in the administration method—whether it is a procedure or an injection,” adding, “The control group for Cartistem is set to undergo debridement. Since the FDA required that the primary endpoint be observed after two years, any temporary or short-term pain-relief effects that might occur in the control group are likely to be mitigated.”

Increased Success Likely Through Detailed Patient Selection

There are also differences in patient selection. While both clinical trials target patients with KL grades 2–3—which indicate the severity of osteoarthritis on X-rays—CartiStem’s Phase 3 clinical trial distinguished itself through additional criteria.

TG-C applied criteria such as KL grades 2–3 and OARSI grades 1–2 for medial joint space narrowing. In contrast, Cartistem required not only KL grades 2–3 but also modified Outerbridge grades 3–4 femoral cartilage defects. This effectively selected patients who, in addition to having symptoms, had actual tissue that could be regenerated.

The KL classification and cartilage damage grading systems assess different aspects. While the KL classification evaluates general degenerative changes in the joint—such as osteophytes or reduced joint space—the Outerbridge and International Cartilage Regeneration Society (ICRS) standards focus on cartilage lesions. This means that even if localized cartilage damage is severe, the entire joint may not necessarily be in an end-stage osteoarthritis condition. Cartistem increased the likelihood of clinical success by limiting the patient population through an approach that considers both the overall disease stage of the joint and the localized lesions targeted for regeneration.

Furthermore, the U.S. Cartistem clinical trial excludes patients with severe leg alignment abnormalities, complete meniscal tears, or root tears. The upper limit for body mass index (BMI) is 35, which is lower than the 40 set for TG-C. This approach minimizes factors that could persistently cause pain or adversely affect treatment outcomes even after cartilage regeneration.

The fact that positive data has been obtained from Phase 3 clinical trials conducted in other countries to date is another factor raising expectations for success. In a Phase 3 trial conducted by Medipost in Japan, Cartistem demonstrated superiority over the hyaluronic acid injection control group in terms of improvements in WOMAC and ICRS scores. Significant differences were also confirmed for the VAS and WOMAC functional subscores—the key endpoints of the U.S. Phase 3 trial—with p < 0.0001 for each.

In a prior Phase 3 trial conducted in Korea, the percentage of patients who showed an improvement of at least one grade in the ICRS cartilage recovery assessment at the 48-week mark was 97.7% in the Cartistem group and 71.7% in the microfracture group. Furthermore, in long-term follow-up, the Cartistem group showed significant differences in WOMAC scores at the 3-year and 5-year marks and in VAS scores at the 5-year mark.

Furthermore, the participation of key investigators in the U.S. Phase 3 clinical trial—including Brian Cole, Professor of Orthopedic Surgery at Rush University Medical Center in Chicago and Director of the “Cartilage Research and Regeneration Center,” as well as leading institutions and medical staff with extensive clinical experience in cartilage regeneration—is expected to enhance the credibility of the clinical trial and significantly contribute to Cartistem’s future success in the U.S. market.

A Medipost official stated, “We anticipate that entering the U.S. market will propel Cartistem to become a global blockbuster, and we plan to subsequently expand into major global markets such as Europe and China.”