Competition toward the world's first "disease-modifying osteoarthritis drug (DMOAD)" is heating up again. U.S. biotech Biosplice Therapeutics has applied to the U.S. Food and Drug Administration (FDA) for approval of its drug candidate lorecivivint. With no clear success criteria yet presented, the global frontrunner's bid is speeding up the chase by Korea's corporations.
According to market research firm Grand View Research, the global osteoarthritis treatment market is estimated at $5.02 billion (about 6.8 trillion won) in 2024 and is expected to reach $10.89 billion (about 14.7 trillion won) in 2033. The compound annual growth rate (CAGR) from 2025 to 2033 is expected to be 9.0%.
If a DMOAD that slows the disease's progression itself succeeds commercially, some say the market landscape could change dramatically.
◇ A market without benchmarks, U.S. frontrunner bets on a "package"
Biosplice said on the 6th (local time) that it submitted a new drug application (NDA) to the FDA seeking approval of lorecivivint as a treatment for knee osteoarthritis. It is the first attempt to knock on the FDA's door with a new drug under the DMOAD concept.
Since early development in 2011, Biosplice has foregrounded "fundamental treatment" that slows the disease's progression itself. Lorecivivint is a small-molecule compound injected into the knee joint space that simultaneously inhibits two kinases involved in inflammation and cartilage damage, and modulates the Wnt signaling pathway, which, when overactivated, drives cartilage destruction.
However, clinical results so far have fallen short of expectations. The company conducted three global phase 3 trials (OA-10, OA-11, OA-21), but all failed to meet the primary endpoints. The primary endpoint in these trials was change in the numeric rating scale (NRS) for pain at week 12, and statistical significance was not achieved.
The core basis of this NDA is OA-07, a long-term extension study of patients who participated in OA-11. The primary endpoint of OA-07 was change in mJSW, the medial joint space width of the knee. The strategy was to reinforce the positive signals observed as secondary endpoints in earlier trials through long-term follow-up.
But OA-07 also did not cross the statistical significance threshold (P<0.05) for the primary endpoint. At year 2 of dosing, the mJSW difference between the treatment and placebo groups was 0.09 mm (P=0.233), and 0.14 mm (P=0.061) at year 3. Among secondary endpoints, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score showed a meaningful improvement with a P value of 0.035 at week 48, but critics said it was insufficient to offset the primary endpoint's limitations.
The trial design also drew controversy. OA-07 proceeded as a single-blind, placebo-controlled study for the initial 48 weeks, then switched to an open-label, uncontrolled phase. A single-blind design in which investigators know the treatment arm, and long-term follow-up without a control arm, impose structural constraints on data interpretation.
Even so, some say Biosplice's latest attempt is meaningful. It is the first case to formally present to the FDA the "possibility of slowing disease progression" by combining structural changes, functional measures, and long-term follow-up data.
To date, the FDA has not provided clear criteria on whether to consider patient-reported outcomes (PRO) such as pain relief and functional improvement, or imaging-confirmed structural changes, as decisive evidence of "fundamental treatment." In this regulatory gap, corporations are designing clinical strategies based on their own interpretations.
◇ Korean corporations aim to catch "two rabbits"…who will win
Korean corporations are targeting the U.S. market with strategies that capture both PRO and structural change. Kolon TissueGene, MEDIPOST, and Bio Solution, which have domestic approval or sales experience with knee osteoarthritis treatments, are representative. They are attempting to clear the FDA threshold based on accumulated clinical data and real-world evidence (RWE).
Kolon TissueGene is conducting a U.S. phase 3 trial of the cell and gene therapy TG-C (formerly Invossa). TG-C is injected into the knee joint space as a mixture, at a 3-to-1 ratio, of allogeneic cartilage-derived chondrocytes and irradiated, proliferation-suppressed transduced cells that express the TGF-β1 gene. In the U.S. phase 3, patient dosing has been completed and roughly two years of follow-up is underway, with a goal of disclosing primary endpoint results in July this year.
Kolon TissueGene set change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score and the visual analog scale (VAS) as the primary endpoints of the U.S. phase 3. The two measures each achieved statistical significance along with structural change in the domestic phase 3 and the U.S. phase 2, respectively.
MEDIPOST is pushing to enter a U.S. phase 3 trial with Cartistem, an allogeneic umbilical cord blood-derived mesenchymal stem cell therapy. Last month it submitted an investigational new drug application (IND) to the FDA and has confirmed the possibility of skipping phase 2. If the IND is approved, observers say the development timeline could be significantly shortened.
In a phase 3 trial conducted in Japan, MEDIPOST set the improvement rate in cartilage defect severity (ICRS grade), along with changes in pain and function measures, as key endpoints, and results are expected to be released in the first half.
Bio Solution is preparing a U.S. phase 3 next year with Cartilife, an autologous chondrocyte therapy. In 2023 it received regenerative medicine advanced therapy (RMAT) designation from the FDA and expects benefits such as expedited review and rolling review. In the U.S. phase 2, it reportedly observed positive signals with primary endpoints set as the cartilage defect filling score at 48 weeks post-surgery (mOC) and the Knee injury and Osteoarthritis Outcome Score (KOOS) for functional improvement.
For now, market attention is focused on Kolon TissueGene, which is progressing the fastest. However, there remains a possibility that TG-C will face a more stringent process than lorecivivint during FDA review. Gene therapies require higher safety standards than small molecules.
Wi Hae-joo, an analyst at Korea Investment & Securities Co., said, "If the U.S. phase 3 succeeds, it could become a symbolic breakthrough for Korea's sluggish pharmaceutical industry, which has lacked innovative new drugs."