Lorecivivint
Lorecivivint (SM04690)
Also known as: SM04690
An injected Wnt-pathway small molecule for knee osteoarthritis whose two published Phase 3 pain trials both missed their primary endpoint, now filed with the FDA in January 2026 on long-term joint-space-width data instead.
Overview
Lorecivivint inhibits CLK and DYRK1A kinases to modulate Wnt signaling in the joint, aiming to slow cartilage loss rather than only relieve pain. Its two published Phase 3 pain trials, OA-10 (498 patients) and OA-11 (513 patients), each failed to beat placebo on the primary pain endpoint at week 12, with a post-hoc signal only in the less structurally severe Kellgren-Lawrence grade 2 subgroup. Biosplice's long-term OA-07 data reported preservation of joint-space width over several years, and the company submitted a New Drug Application on January 6, 2026. If approved it would be the first structure-modifying osteoarthritis drug, but the published randomized evidence for symptom relief is negative.
Mechanism of action
Intra-articular CLK/DYRK1A inhibition that modulates Wnt signaling, reducing inflammation and promoting chondrocyte health.
Key studies & citations
- Human2026
Biosplice submits NDA for lorecivivint in knee osteoarthritis
Filing based on joint-space-width preservation.
Biosplice press release - Human2025
A Phase 3, 56-week, randomised, double-blind, placebo-controlled study (OA-11) utilising patient-reported and radiographic outcomes evaluating the efficacy and safety of a lorecivivint injection in patients with moderate to severe knee osteoarthritis
513 patients. A single injection missed the primary endpoint: pain NRS change at week 12 was -2.24 on lorecivivint against -2.49 on placebo (p=0.185), with no treatment effect on the other endpoints. Neither group lost meaningful medial joint space width over 52 weeks.
Clinical and Experimental Rheumatology - Human2025
A Phase 3, 28-week, multicentre, randomised, double-blind, placebo-controlled trial (OA-10) to evaluate the efficacy and safety of a single injection of lorecivivint in the target knee joint of moderately to severely symptomatic osteoarthritis patients
498 patients; lorecivivint again failed the primary pain endpoint against placebo. A post-hoc analysis found a signal in the less structurally severe Kellgren-Lawrence grade 2 subgroup, which the authors present as a hypothesis for earlier intervention, not a result.
Clinical and Experimental Rheumatology
Frequently asked questions
How is this different from BPC-157 for joints?
Lorecivivint has completed regulated Phase 3 trials with imaging endpoints and is under FDA review. BPC-157 has animal data only.
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