[Edaily Reporter Kim Jinsoo ] As the global population continues to age, the number of patients with knee osteoarthritis is rapidly increasing. Consequently, active research is underway in South Korea to develop a disease-modifying osteoarthritis drug (DMOAD) based on mesenchymal stem cells (MSCs).

Research and development of mesenchymal stem cell-based osteoarthritis treatments is proceeding on the basis of their high safety profile. However, as it is difficult to prove their efficacy, demonstrating effectiveness in Phase 2 clinical trials and confirming a correlation with cartilage regeneration are expected to be key points in their development.

Limitations of Mesenchymal Stem Cell-Based Osteoarthritis Treatments?

According to ClinicalTrials.gov, the U.S. National Institutes of Health (NIH) clinical trial information portal, as of the 18th, there are more than 200 clinical studies related to osteoarthritis treatments using mesenchymal stem cells. In South Korea, companies such as MEDIPOST CO., LTD.(078160), KANGSTEM BIOTECH CO., LTD.(217730), and NATURECELL CO.,LTD.(007390) are developing fundamental treatments for osteoarthritis based on mesenchymal stem cells. Among these, MEDIPOST CO., LTD.’s SMUP-IA-01 and KANGSTEM BIOTECH CO., LTD.’s Oscar are being developed as injectable formulations, offering greater convenience as fundamental treatments.

A key strength of mesenchymal stem cell-based therapies is their high safety profile. Mesenchymal stem cells are non-hematopoietic adult pluripotent stem cells; they are multipotent cells capable of differentiating only into bone or cartilage, rather than possessing the totipotency to differentiate into all types of tissue. Consequently, the risk of forming teratomas or malignant tumors is extremely low.

Regarding administration methods, it is known that intra-articular injections of MSCs do not result in a statistically significant increase in drug-related adverse reactions compared to a placebo. As such, the development of mesenchymal stem cell-based treatments for osteoarthritis is proceeding very actively. However, only a very small number of cases have actually reached marketing approval. This is because, while mesenchymal stem cells are highly safe, it is difficult to prove their efficacy and mechanism of action.

Mesenchymal stem cell-based therapies face fundamental challenges primarily regarding efficacy and mechanism of action. First, mesenchymal stem cells vary in their secretome and functional properties depending on the donor, making it difficult to predict their efficacy on an individual patient basis.

In fact, according to several randomized controlled trials (RCTs) conducted in 2024 (“Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials” and “Relative efficacy and safety of mesenchymal stem cells for osteoarthritis: a systematic review and meta-analysis of randomized controlled trials”), it was not confirmed that mesenchymal stem cells significantly improve knee pain and function. The difficulty in confirming the clinical significance of mesenchymal stem cells as a treatment for osteoarthritis is seen as a key factor preventing regulatory approval.

It is true that mesenchymal stem cells can differentiate into chondrocytes. However, there is very limited direct evidence that they reliably differentiate into chondrocytes within joints subjected to inflammatory and mechanical stimuli to form a normal chondral extracellular matrix. Although cartilage regeneration has been observed in animal models and some clinical trials, most studies suggest that the primary mechanism of action is paracrine (local secretion) effects rather than regeneration through differentiation.

Phase 2 Clinical Trials to Confirm Efficacy Are Key

Accordingly,

Phase 2 clinical trial

data confirming

efficacy

are expected to be pivotal in the development of mesenchymal stem cell therapies for osteoarthritis. In fact, regarding MEDIPOST CO., LTD.’s SMUP-IA-01, Phase 2 clinical trial data released in 2024 confirmed safety, as no immune reactions or serious adverse drug reactions occurred. However, questions remain regarding its efficacy.

In terms of changes in the total score of the “WOMAC” functional index for knee pain and function, the treatment showed a statistically significant improvement in symptoms compared to baseline. However, it failed to demonstrate superiority over the control group, which received sodium hyaluronate injections. MEDIPOST CO., LTD. plans to apply for a Phase 3 clinical trial of SMUP-IA-01 in South Korea in the second half of this year. However, MEDIPOST CO., LTD. has not yet disclosed a specific strategy for how it intends to overturn the Phase 2 results.

MEDIPOST CO., LTD. official stated, “SMUP-IA-01 demonstrated efficacy in long-term follow-up results,” adding, “We plan to prove efficacy in the Phase 3 clinical trial by modifying the clinical trial design.”

KANGSTEM BIOTECH CO., LTD. completed the final patient follow-up for the Oscar Phase 2a clinical trial last April and plans to announce topline data this coming July. The Oscar trial plans to evaluate not only subjective endpoints such as the Visual Analog Scale (VAS) for pain and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), but also imaging endpoints including the Magnetic Resonance Imaging (MRI)-based cartilage assessment index (MOCART) and the Knee Osteoarthritis Radiographic Assessment Score (WORMS).

In particular, according to KANGSTEM BIOTECH CO., LTD., Oscar is a product that combines mesenchymal stem cells with acellular cartilage matrix (CAM) and is expected to maximize the cartilage regeneration efficacy of the stem cells. Mesenchymal stem cells play a role in inducing anti-inflammatory and immunomodulatory effects as well as cartilage regeneration, while the acellular cartilage matrix serves as a scaffold that helps the stem cells differentiate into and function as cartilage.

A biotech industry official stated, “The strength of mesenchymal stem cell-based osteoarthritis treatments lies in their superior safety compared to other therapies,” adding, “However, as there are ongoing concerns about inconsistent efficacy, the key to successful development lies in ensuring consistent results and demonstrating a clear correlation with cartilage regeneration.”