Medipost's Cartistem Phase 3 clinical trial succeeds in Japan

The company's first win for overseas approval

Has met all dual primary endpoints, including WOMAC·ICRS…secured statistical significance compared with the HA injection

Patient enrollment for the U.S. Phase 3 clinical trials Patient enrollment for the U.S. Phase 3 clinical trials underway…"Concurrently proceeding with Japanese drug pricing process·U.S. approval based on RWE evidence"

Medipost has met all dual primary endpoints in its Japanese Phase 3 clinical trial for Cartistem, a stem cell therapy for knee osteoarthritis. By securing statistical significance in both subjective symptom improvement and arthroscopic cartilage regeneration compared to the active control group, the company’s efforts for commercialization in Japan and the advancement of its U.S. Phase 3 trials are expected to speed up.

On the 13th, Medipost held a press conference at the Four Seasons Hotel in Jongno-gu, Seoul, to disclose the major results of the Japanese Phase 3 trial for Cartistem and its future global development strategy. Key attendees included Medipost CEO Wonil Oh, Global Business Head and CEO of Medipost K.K. (Japan) and co-CEO of Medipost Inc. (USA) Seung Jin Lee, and Vice President Hoon Sik Cho.

Medipost CEO Wonil Oh

CEO Wonil Oh remarked, "This achievement is a major achievement of Medipost's journey since its founding, driven by the goal of improving patients' quality of life through stem cell therapy innovation," and added, "We will achieve entry into the Japanese market for Cartistem and complete the ongoing U.S. Phase 3 trial to emerge as a global leader in the stem cell industry."

Cartistem is an allogeneic umbilical cord blood-derived mesenchymal stem cell therapy developed by Medipost. It is a treatment aimed at regenerating damaged cartilage and improving pain and function in patients with knee cartilage defects caused by degenerative changes or repeated trauma. Since receiving marketing authorization from the Ministry of Food and Drug Safety (MFDS) in 2012, it has accumulated over 10 years of prescription experience. Cartistem recorded sales of KRW 19.5 billion last year.

Medipost conducted Japanese clinical trials to overcome domestic market growth limitations and secure its first overseas commercial hub. The Japanese Phase 3 trial was designed as a pivotal study for Japanese marketing authorization. Based on its experience in authorization and commercialization, as well as existing clinical data accumulated in Korea since 2012, Medipost was able to skip Phase 1 and 2 trials in Japan and enter directly into Phase 3.

The trial was a randomized, active-controlled comparative study conducted at 13 medical institutions in Japan involving 130 patients with knee osteoarthritis. The actual administration and surgery groups consisted of 59 patients in the Cartistem group and 61 in the hyaluronic acid (HA) group. Patients were followed for 52 weeks after administration to observe efficacy and safety.

The control group received a hyaluronic acid injection, which is the standard of care for patients with knee osteoarthritis in Japan. Global Business Head Seung Jin Lee explained, "In the process of discussing the clinical design with the Japanese Pharmaceuticals and Medical Devices Agency (PMDA), we reflected the fact that Japanese patients generally receive HA injections for knee osteoarthritis treatment and set that product as the control."

The primary subjects were patients with knee osteoarthritis aged 20 to 80. The radiographic severity of osteoarthritis corresponded to K&L grades 2 to 3, and the degree of cartilage damage corresponded to ICRS grades 3 to 4. The size of the cartilage defect ranged from approximately 2 to 9 square centimeters, and the trial included patients with a pain score of 40 or higher on a 100mm Visual Analog Scale (VAS) and a Body Mass Index (BMI) of less than 35. Furthermore, the study targeted patients who had not shown sufficient symptom improvement despite receiving existing treatments, such as exercise therapy, physical therapy, or hyaluronic acid injections, for at least 3 months.

According to the presentation, Cartistem met both dual primary endpoints in the Japanese Phase 3 trial. The dual primary endpoints were ▲the change in the WOMAC total score ▲the improvement rate of one or more ICRS grades. WOMAC is a patient-reported outcome that evaluates knee pain, functionality, and stiffness as perceived by the patient. ICRS is a structural evaluation metric used to confirm whether the degree of cartilage damage has actually improved through arthroscopy. The design required both metrics to be met for the trial to be considered a success.

Lee explained, "Since Cartistem is administered via surgery and HA via injection, patients inherently know which treatment they received, which can allow for a placebo effect in patient-reported metrics," and added, "To compensate for this, we included the ICRS evaluation, which directly checks the cartilage state via arthroscopy at the 52-week mark, as a co-primary endpoint. To ensure the treatment group information remained undisclosed, evaluations were conducted by a separate central adjudication committee after blinding the data."

Medipost CEO Wonil Oh, Global Business Head and CEO of Medipost K.K. (Japan) and co-CEO of Medipost Inc. (USA) Seung Jin Lee, and Vice President Hoon Sik Cho

Clinical results showed that Cartistem demonstrated statistically significant superiority in changes in the WOMAC total score compared with the HA group. The WOMAC p-value was reported as <0.0001. Cartistem also showed a significant improvement over the active control group in the rate of improvement in one or more ICRS grades, with an ICRS p-value of 0.0002.

Consistent results were also confirmed in the secondary endpoints. The VAS for pain level and the IKDC and KOOS for knee functionality all recorded p-values of less than 0.0001. Significant improvements were also observed across all WOMAC sub-items, including pain, functionality, and stiffness.

"This Japanese Phase 3 study was designed so that it had to meet both dual primary endpoints," Lee said. "It is highly significant in that we confirmed not only the improvement in pain and function felt by the patient but also the regeneration of cartilage via arthroscopy," and added, "In the U.S. or Europe, a design that performs arthroscopy on patients again is not easy due to the high patient burden and ethical considerations, as it involves anesthesia and invasive procedures. Therefore, the ICRS data secured in the Japanese Phase 3 will be highly valuable data to be utilized overseas."

Medipost plans to apply for Japanese marketing authorization in the second half of this year based on these clinical results. Given the PMDA review period, the company aims to obtain approval by the end of 2027. It plans to pursue a launch in the Japanese market, followed by subsequent processes for price setting and insurance reimbursement.

The company expressed strong confidence regarding the possibility of Japanese marketing authorization. Lee stated, "Due to the nature of cell and gene therapies, CMC (which refers to manufacturing process management and quality consistency), inspections of our GMP facility in Guro, Korea, and our local production partner's facility in Japan, remain." However, Lee said, "After reviewing these results with external experts, including advisory panels and former PMDA officials, we received the opinion that with clinical results indicate there should be no major issues in gaining marketing authorization."

The local partner, Teikoku Pharma, will handle sales in Japan. Previously, Medipost signed an exclusive distribution agreement for Cartistem in Japan with Teikoku Pharma in December last year. The company has already received a non-refundable upfront payment of USD 8 million, with an additional USD 10 million payable upon marketing authorization. Lee explained, "The marketing authorization holder will be Medipost K.K., the Japanese subsidiary of Medipost, and Medipost will also manage the responsibility for manufacturing and shipping. Teikoku Pharma will be responsible for transportation, sales, and marketing within Japan."

Considering the price-setting and insurance reimbursement procedures following Japanese marketing authorization, Medipost is also conducting a Real-World Evidence (RWE) study in South Korea. The company explained that it has secured data from approximately 550 patients who underwent Cartistem procedures at 13 Korean medical institutions, with an average follow-up period of about 6.9 years.

​"Since Cartistem received marketing authorization in Korea in 2012, approximately 36,700 patients have undergone surgery as of the end of last month," Lee emphasized. "Among them, we are collecting real-world evidence data targeting patients who have passed at least three years since their procedure."

Lee continued, "The endpoint we consider most important is the rate of conversion to total knee artificial joints. From the data of 550 patients secured so far, we have identified that less than 1% of patients have converted to artificial joints." He added that detailed information would be disclosed at the end of the year. The company intends to use this data as reference material for the Japanese marketing authorization application and as evidence during the price-setting and insurance reimbursement negotiations with the Ministry of Health, Labor and Welfare after approval.

Lee noted, "In Japan, the process of price setting and insurance reimbursement with the Ministry of Health, Labour and Welfare proceeds after marketing authorization. How many years a patient maintains the effect after receiving Cartistem, and the rate at which they transition to other treatments or artificial joint surgery, can be vital data for economic evaluations," and stated, "This real-world evidence study will serve as an important basis not only for Japan but also for discussions with insurance companies in the U.S. after obtaining approval there."

Regarding the company's U.S. Phase 3 clinical trial, patient enrollment is currently underway following the U.S. Food and Drug Administration (FDA) approval of the IND application earlier this year. The company plans to use the results of the U.S. Phase 3 trial, along with the Japanese Phase 3 data and Korean RWE, as materials for the U.S. marketing authorization application.