J. Tambiah (San Diego, US)

Biosplice Therapeutics Inc
Dr. Tambiah is a physician with expertise in medical affairs; early and late phase clinical development; translational medicine; and health outcomes research. Prior to Biosplice; he worked for UCB Pharma holding medical affairs leadership roles within their immunology franchise in the UK and US. Prior to joining the pharmaceutical industry; he trained and practiced in cardiothoracic surgery at Guys’ and St. Thomas’ Hospitals in London. Dr. Tambiah gained his UK medical qualifications at the Universities of St. Andrews and Manchester; and his doctorate degree in vascular immunology as a Wellcome Fellow at Imperial College; London. He has won many awards for research and authored papers. In addition; he is an Affiliate Member of the Faculty of Pharmaceutical Physicians; UK.

Presenter Of 1 Presentation

 ICRS 2022 - Online Programme
Podium Presentation Osteoarthritis

24.3.6 - Safety and Efficacy of Lorecivivint in Knee Osteoarthritis: A Post Hoc Analysis From an Observational Extension Study

Presentation Topic
Osteoarthritis
Date
15.04.2022
Lecture Time
11:18 - 11:27
Room
Bellevue
Session Name
24.3 - EOA II - Progress & Innovation
Session Type
Free Papers
Speaker
Authors
Disclosure
Ismail, Christopher, Heli, Sarah, Jeyanesh, and Yusuf are employees, shareholders, or consultants of Samumed, LLC. Nebojsa was a consultant for Pfizer, Regeneron, and Orthofix.

Abstract

Purpose

Lorecivivint (LOR) is a novel, investigational, intra-articular (IA) CLK2/DYRK1A inhibitor that modulates the Wnt pathway to potentially treat knee osteoarthritis (OA). We analyzed a 5-year, Phase 3, multicenter, observational extension study for safety and efficacy in subjects with moderate to severe knee OA.

Methods and Materials

Pooled data from 6-, 12-, 24-, and 36-month visits for completer subjects (NCT02951026) from Phase 2a (NCT02536833) and 2b (NCT03122860) LOR trials were analyzed. Subjects received a single LOR or control injection at baseline. Safety outcomes included adverse events (AEs) and serious AEs (SAEs). Efficacy outcomes included WOMAC Pain and Function subscores, analyzed by baseline-adjusted ANCOVA, and radiographic medial joint space width (mJSW). A post hoc analysis of 0.07 mg LOR versus control in a subject subgroup (unilateral symptoms, no widespread pain, 18-month radiograph at study termination) was performed.

Results

Overall, 584/703 (83%) subjects completed the study (mean age 60.7 years, mean BMI 29.1 kg/m2, female 61%, KL 3 OA 61.2%). In the safety analysis set (LOR, n=495; control, n=208), 169 AEs were reported by 110 (15.6%) subjects. AE rates were similar between groups. Four AEs in 3 (0.6%) subjects were treatment related; none involved subject withdrawal. Sixty-eight SAEs (none treatment related) were reported by 38 (5.4%) subjects, with one death in the control group. LOR (n=59) showed greater improvements from baseline in WOMAC Pain and Function at 6 (Pain: -8.16, 95% CI [-15.60, -0.71], P=0.032; Function: -9.47 [-17.09, -1.84], P=0.015) and 12 (Pain: -8.51 [-15.17, -1.85], P=0.013; Function: -9.62 [-16.83, -2.42], P=0.009) months versus control (n=70) (Figure 1). No meaningful mJSW progression occurred in any group over 18 months. Limitations included post hoc analysis of small completer groups.

Conclusion

In this post hoc analysis, a single 0.07 mg LOR injection appeared well tolerated in knee OA subjects and demonstrated symptom improvements for up to 12 months versus control.

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