BONE ANABOLIC EFFECTS OF A NOVEL ORALLY-AVAILABLE SMALA MULTICENTER, OBSERVATIONAL, EXTENSION STUDY EVALUATING THE SAFETY, TOLERABILITY, AND EFFICACY OF A SINGLE LORECIVIVINT INJECTION IN KNEE OA SUBJECTS
Authors: Ismail Simsek et al.
In this 5-year phase 3 observational extension study of completer subjects from a 12-month phase 2a (Yazici, Y. et al., Arthritis Rheumatol. 2020) and a 6-month Phase 2b (Yazici, Y. et al.Osteoarthr. Cartil. in press), the safety, tolerability and efficacy of Lorecivivint (LOR), a novel intra-articular CLK/DYRK inhibitor that modulates Wnt and inflammatory pathways, was studied. Subjects received a single LOR or vehicle placebo (PBO) injection at their phase 2 parent-trial baseline visit (Month 0). Pooled data from clinic visits at 6, 12, 24, and 36 months were used to analyse outcomes.
Efficacy analyses demonstrated that subjects in the 0.07 mg LOR group (n=59) showed greater mean improvements from baseline in both WOMAC pain and function at 6 and 12 months vs. subjects in the control group (n=70). No mJSW progression was observed in any group over 18 months. Four AEs in 3 (0.6%) subjects across LOR groups were considered related to the study drug; no subjects withdrew from the study due to a treatment-related AE. Incidence was similar between LOR and PBO groups. Sixty-eight SAEs in 38 (5.4%) subjects were reported with none considered related to treatment by investigators
Lorecivivint appeared safe and well tolerated. Efficacy analyses on the described subset of completer subjects demonstrated durable symptom improvements in WOMAC Pain and Function for up to 12 months vs. controls. A larger placebo-controlled phase 3 study is necessary to proof this preliminary data in a larger population.
Lorecivivint seems to be an interesting new intraarticular compound with long term efficacy and good safety in patients with knee osteoarthritis.