CartiLife, an autologous cartilage-derived chondrocyte cell therapy for regenerating knee cartilage, will be easier to inject with a new injector, industry officials said.

CartiLife won a conditional nod from the Ministry of Food and Drug Safety in April 2019 to treat knee cartilage defects (ICRS Grade 3 to 4 with defect sizes of 2-10 square centimeters).

In clinical trials, 90 percent of patients treated with CartiLife had regenerated cartilage after one year of treatment. The treatment also proved the long-term effect, as regenerated cartilage was maintained for up to five years.

In addition, physicians will find it more convenient to perform a CartiLife procedure with a new injector.

Korea Biomedical Review (KBR) sat down with Jung Min-kyung, associate project manager at Specialty Care BU of Mundipharma Korea, and Lee Jeong-yun, a senior researcher at Biosolution, to hear about the background of CartiLife’s transformation, clinical trials, and sales and marketing plans.

KBR: A CartiLife procedure involves cleaning up damaged cartilage and transplanting the cultured cartilage tissue. The treatment is different from existing therapies in terms of the procedure and the use of pellet-type tissue. Can you tell us why Biosolution decide to develop this product?

Lee: Unlike existing treatments, a CartiLife procedure involves a simple clean-up of the lesion and transplantation of the prepared tissue without a separate process such as making a fine hole in the subchondral bone. So, it takes a short time. Therefore, cleaning up damaged cartilage legion is not a burdensome task for an orthopedic surgeon. Also, unlike suspension treatments, CartiLife involves the implantation of solid pellets (beads), which enables the cartilage to fill up faster. In addition, CartiLife is the world’s only product made of hyaline cartilage among authorized knee cartilage defect treatments.

KBR: How did doctors first react to CartiLife?

Jung: Even in a virtual meeting, they show great interest in explaining the CartiLife development background, mechanism of action, and clinical data. We met many physicians who wanted to experience the most advanced cartilage defect treatment clinically. After talking with doctors who performed CartiLife procedures, we found that more than 90 percent of them were satisfied because of a good prognosis three months after the procedure.

KBR: What is the strongest advantage of CartiLife?

Lee: In general, cartilage tissue generated by other treatments is usually fibrocartilage. But in CartiLife treatment, hyaline cartilaginous tissue is cultivated outside and transplanted in the defect site. So, the quality of the regenerated cartilage is excellent. In addition, the cultured cartilage tissue is in pellets, which shows more structural regeneration than the conventional suspension treatments. For this reason, the rehabilitation period using CartiLife is six weeks, much shorter than that of existing treatments.

KBR: We heard that CartiLife’s injector would be changed soon. Why do you have to change the injector when only a year and a half since the market release? Also, the existing injector has been used until phase 2 studies. We wonder if there will be any difference in treatment results with the new injector.

Lee: We decided to change the injector to improve convenience for physicians. As the product remains the same, the change will not affect the therapeutic effect. The change of the injector reflected the opinions of physicians who used it after the market release. This reflects the opinion that pellets may remain inside the existing silicone NGO catheter. So, we designed a funnel-shaped injector to make the most of the product without leftover pellets and separately made a pusher to use up the remaining pellets.

Jung: It was part of Biosolution’s efforts to actively receive feedback from doctors and find ways to respond quickly.

KBR: When do you plan to change the injector to a new one?

Lee: We have completed the development of the new injector, but we have to submit separate test results and obtain approval from the Ministry of Food and Drug Safety. So, we expect that the new injector will be used for patient care around the end of this year or early next year.

KBR: How many medical institutions can perform a CartiLife procedure, and how large are they?

Jung: As of the end of August, about 80 hospitals across the nation could perform the procedure. Approximately 40 percent of them are university hospitals, and the rest are spine and joint hospitals.

KBR: How is CartiLife trial going?

Lee: CartiLife won conditional approval after a local phase 2 trial, and a phase 3 study has been ongoing since last year. In May last year, we enrolled the first patient and in August, we started the procedure in the treatment group. We have recruited 75 patients so far and plan to enroll a total of 104 patients by the end of the year. We also began a phase 2 study in the U.S. and started recruiting patients.

KBR: Who are CartiLife’s target patients?

Jung: We focused marketing activities on patients aged 50 or younger who have ICRS (International Cartilage Regeneration & Joint Preservation Society) Grade 3 or 4 cartilage defects. Until early this year, the average age of CartiLife-treated patients was 46.6.

Recently, with accumulated experience of doctors, the target patient group is broadening to those in the late 50s or early 60s and even patients withK&L (Kellgren & Lawrence) Grade 3. As of the end of August this year, the average age of CartiLife-treated patients went up to about 50.

KBR: Patients may think that a more skillful doctor’s treatment and younger patient age could raise the effect of cartilage regeneration. Is this true?

Lee: Individual doctors’ skill levels do not affect the treatment result because of the simple CartiLife procedure. In a test by Biosolution’s lab, the effect has nothing to do with age.

A slight difference in the regeneration result comes from different cellular characteristics of individual patients rather than age. The MFDS’ authorization states that it can be used regardless of age. Some patients in their 70s have also received CartiLife procedures.

KBR: Can you explain CartiLife’s long-term follow-up data and adverse reactions?

Lee: We have confirmed the data of five-year follow-up data of the local phase 1 study. We also plan to continue to track five-year data of a local phase 2 trial and 10-year data of the phase 1 study. Until the domestic phase 2 trial, no serious adverse reaction was reported. Occasionally, some patients had their cartilage slightly bulging than the original cartilage height, but this was confirmed only through MRI scans, and there was no problem at all with the naked eye. It did not cause any health issues such as pain.