The Novel, Intra-Articular Clk/Dyrk1a Inhibitor Lorecivivint (Sm04690), A Wnt Pathway Modulator, Improved Responder Outcomes In Subjects With Knee Osteoarthritis: A Post Hoc Analysis From A Phase 2b Trial

Background: Lorecivivint (LOR; SM04690) is a small-molecule, intra-articular (IA) CLK/DYRK1A inhibitor that modulates the Wnt pathway1 and has demonstrated some beneficial effects on patient-reported outcomes (PROs) relative to placebo (PBO) in two Phase 2 knee OA trials. With subjective measures such as PROs, meaningful benefits may be better characterized by representation as discrete threshold responses rather than by changes in mean point estimates. Objectives: To conduct a post hoc analysis of subjects in a 24-week Phase 2b study by measuring the proportions of subjects treated with LOR and placebo (PBO) who achieved 30%, 50%, or 70% threshold responses of improvement over baseline in Pain Numeric Rating Scale (NRS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain, WOMAC Function, and Patient Global Assessment (PtGA) at Week 12. Results from the Phase 3-selected dose of 0.07 mg LOR are presented here. Methods: Subjects had ACR-defined knee OA, Kellgren-Lawrence (KL) grades 2–3, and Pain NRS scores ≥4 and ≤8 in the target knee and Results: In total, 635 subjects (91.4%) completed the study (mean age 59.0±8.5 years, BMI 29.0±4.0 kg/m2, female 58.4%, KL grade 3 57.3%). At Week 12, treatment with 0.07 mg LOR significantly (P Conclusion: In this post hoc analysis, LOR-treated subjects reported greater improvements in PRO threshold responses versus PBO from Week 12 through Week 24. LOR demonstrated significantly higher odds of achieving and maintaining improvements in PROs at 30% and 50% thresholds. Phase 3 studies of 0.07 mg LOR are ongoing. References: [1]Deshmukh V, et al. Osteoarthr Cartil. 2019. Disclosure of Interests: Yusuf Yazici Shareholder of: Samumed, LLC, Grant/research support from: Bristol-Myers Squibb, Celgene, and Genentech, Consultant of: Celgene and Sanofi, Employee of: Samumed, LLC, Sarah Kennedy Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Christopher Swearingen Shareholder of: Samumed, LLC, Employee of: Samumed, LLC, Jeyanesh Tambiah Shareholder of: Samumed, LLC, Employee of: Samumed, LLC