[Edaily Reporter KIM JI-WAN ] The value of the exclusive domestic distribution rights for “Lorecivivint,” a new osteoarthritis drug secured by SamilPharmaceutical(000520), is expected to be reevaluated. This follows the failure of Kolon TissueGene, Inc.(950160)’s “TG-C” to meet both co-primary endpoints—pain and joint function—in its first U.S. Phase 3 clinical trial. The two treatments have been competing for the title of the world’s first curative treatment for osteoarthritis.

According to SamilPharmaceutical on the 21st, the company holds the rights to the domestic development, approval, and exclusive commercialization of Loresibivint, developed by Biosplice. Previously, in January, Biosplice submitted a New Drug Application (NDA) for Loresibivint to the U.S. Food and Drug Administration (FDA).

As uncertainty surrounding the approval of the competing candidate, TG-C, has grown, Loresibivint has emerged as the candidate closest to becoming the world’s first disease-modifying osteoarthritis drug (DMOAD). Consequently, analysts say the strategic value of SamilPharmaceutical’s domestic rights to Loresibivint has increased significantly.
Lore-Sibiv

int Takes the Lead… Strong Contender for the DMOAD Title

Following the failure of TG-C’s first Phase 3 trial, Biosplice’s Lore-Sibivint has garnered relatively more attention.

BioSplice defines Loresibivint as the first osteoarthritis drug candidate with disease-modifying potential to have entered the FDA application stage. With no DMOADs having yet received FDA approval, Loresibivint has effectively emerged as the frontrunner.

An official from SamilPharmaceutical explained, “Loresibivint is a small-molecule injectable administered into the knee joint cavity once or twice a year,” adding, “It selectively inhibits the kinases ‘DYRK1A’ and ‘CLK2,’ which are involved in inflammation and cartilage degradation.”

It reduces inflammatory cytokines and chondrolytic enzymes by inhibiting DYRK1A, and regulates Wnt signaling by inhibiting CLK2. In other words, it works by promoting chondrocyte formation and protecting free cartilage. In clinical trials, Loresibivint actually slowed the deterioration of joint structure, unlike existing anti-inflammatory analgesics that merely reduce pain.

In the “OA-07” long-term extension Phase 3 clinical trial, the LoerciVint treatment group showed significant improvements in pain at the 6-month mark and in pain and function at the 12-month mark compared to the placebo group. Long-term radiographic analysis also revealed structural signs indicating that the medial knee joint space width was maintained or improved.

Specifically, in an analysis of patients who completed the OA-07 trial, the medial joint space width in patients treated with LoerCivibint for 3 years decreased by 0.06 mm from baseline, whereas in patients receiving the placebo, it decreased by 0.21 mm prior to crossover. The difference between the two groups at the comparison time points was 0.15 mm, and this difference was statistically significant. The WOMAC pain score also showed greater improvement with Loerci-Vibin compared to the placebo, with a 4.52-point improvement at Week 24 and a 5.19-point improvement at Week 48, both of which were statistically significant.

He explained, “Joint space width is an indicator that indirectly reflects the condition of knee cartilage,” adding, “As osteoarthritis progresses and cartilage wears down, the space between the bones narrows.” He went on to predict, “If Roersibivint is recognized for inhibiting not only pain but also the narrowing of joint space, it has the potential to secure the status of the world’s first DMOAD.”

TG-C Fails to Outperform Placebo in Both Pain and Function

In contrast, for TG-C, while the VAS score—which measures pain—decreased by an average of 38.7 points in the TG-C group compared to baseline, the placebo group also saw a decrease of 39.2 points. The difference between the groups was only 0.5 points, and the p-value was 0.8322. This was well above the general threshold of 0.05 used to determine statistical significance.

The same was true for the WOMAC total score, which comprehensively evaluates pain, joint stiffness, and physical function. The TG-C group showed a decrease of 27.61 points, while the placebo group showed a decrease of 26.54 points. The difference between the groups was only 1.07 points, and the p-value was 0.5701. Neither metric demonstrated a difference in efficacy between TG-C and the placebo.

The company drew a clear line regarding criticism that its previously conducted Phase 3 “OA-10” and “OA-11” trials for Lowersibivint also failed to meet their primary endpoints.

A representative from SamilPharmaceutical explained, “Since these trials were conducted during the COVID-19 pandemic, both the treatment and placebo groups minimized outdoor activities, significantly reducing the frequency of exposure to knee pain associated with physical activity.” The representative added, “During this process, pain scores in the placebo group improved more than expected, which is believed to have diluted the difference in efficacy between the two groups.”

The spokesperson continued, “In subsequent long-term, repeated-dose clinical trials, the Roer-Civibint treatment group showed significant improvements in pain and function compared to the placebo group, and structural benefits, such as the maintenance of joint space, were also confirmed,” emphasizing, “It is difficult to judge the efficacy of Roer-Civibint based solely on the results of the earlier clinical trial.”

SamilPharmaceutical: Reevaluation of the Value of Exclusive Domestic Rights

The reason Roer-Sibivint’s potential FDA approval is drawing attention in Korea is SamilPharmaceutical.

In 2021, SamilPharmaceutical signed a technology licensing agreement with BioSplice, securing the rights to develop, obtain approval for, and exclusively commercialize Loresibivint in South Korea. Under this structure, SamilPharmaceutical leads domestic clinical trials, product approval, and sales.

The total contract value, including the upfront payment and milestones for clinical trials, approval, and commercialization, amounts to a maximum of $70 million (103.5 billion won). After the product’s launch, BioSplice will receive double-digit sales royalties from SamilPharmaceutical.

An industry insider noted, “If TG-C had met its primary endpoint in its first U.S. Phase 3 trial, the two drugs would likely have competed fiercely for the title of the world’s first DMOAD,” adding, “However, with TG-C’s approval timeline hitting a snag, Roer-Sibivint’s time advantage has become even more pronounced.”

The source continued, “If Roer-Cibivint is approved in the U.S., SamilPharmaceutical will become the company holding exclusive domestic rights to the world’s first DMOAD,” adding, “Development risks could also be significantly reduced, as U.S. approval data can serve as a key basis for domestic marketing authorization and reimbursement strategies.”

Meanwhile, there are approximately 3.07 million patients with knee osteoarthritis in South Korea, and the industry estimates that the number of patients with KL grades 2–3—the primary target population for Loresibivint—ranges from 2 million to 2.7 million. Applying the annual treatment cost of 3 million won for Roersibivint—which SamilPharmaceutical is currently reviewing—the potential market is estimated to be between 6 trillion and 8 trillion won. Even assuming a market penetration rate of just 3%, annual sales would reach 180 billion to 240 billion won, and at 5%, they would reach 300 billion to 400 billion won.