Lorecivivint, an intra-articular potential disease-modifying osteoarthritis drug

ABSTRACT

Introduction: Osteoarthritis (OA) is the most common form of arthritis. Knee OA is associated with joint pain, activity limitation, physical disability, reduced health-related quality of life, and increased mortality. To date, all pharmacologic treatments for OA are directed toward pain management. Lorecivivint (LOR) is an investigational agent that has potential as a disease-modifying osteoarthritis drug (DMOAD). It modulates the Wnt signaling pathway by inhibiting CDC-like kinase 2 and dual-specificity tyrosine phosphorylation-regulated kinase 1 A which are molecular regulators in Wnt signaling, chondrogenesis, and inflammation.

Areas covered: This paper discusses the current pharmacologic guidelines for the treatment of knee OA and illuminates the potential of a new agent, Lorecivivint, as a disease-modifying osteoarthritis drug (DMOAD). Efficacy and safety and the challenges for this novel agent come under the spotlight.

Expert opinion: LOR may be a potential DMOAD for the treatment of patients with knee OA. While the Phase 2A trial did not meet its primary endpoint, preplanned analyses did identify a target population for further evaluation of its potential as a DMOAD. Phase 3 trials are ongoing, but this intra-articular drug is currently considered safe and well tolerated, with no significant reported systemic side effects.

KEYWORDS:

• Lorecivivint
• osteoarthritis
• knee osteoarthritis
• wnt signaling
• disease-modifying osteoarthritis drug
• dmoad
• clinical trial

Article highlights

• Osteoarthritis is the most common form of arthritis. Knee OA is associated with pain, activity limitation, and physical disability.

• To date, all pharmacologic therapies for knee OA are directed towards symptomatic management.

• Lorecivivint (LOR) is a small molecule that modulates the Wnt signaling pathway. It is now being investigated as both an analgesic agent and a potential disease-modifying osteoarthritis drug.

• Data from a Phase 1 trial showed that LOR was safe and well tolerated. While the Phase 2A trial did not meet its primary endpoint, pre-planned analyses did identify a target population for further evaluation of the potential efficacy of LOR as a DMOAD in Phase 2B. Phase 3 trials are ongoing.

• This intra-articular drug was considered safe and well tolerated, with no significant reported systemic side effects.

• There are challenges for the use of lorecivivint in the treatment of symptomatic knee OA. It is administered by intraarticular injection which might limit the number of providers who will be able to use it. Also, to verify that the drug is administered in the joint space, and to exclude the possibility of drug leak, lorecivivint is administered under ultrasound guidance.

This box summarizes key points contained in the article.

Box 1. Drug summary box

Declaration of interest

MC Hochberg has performed consulting activities, including attendance at Advisory Board meetings, for Bone Therapeutics, Centrexion Therapeutics, Eli Lilly, EMD Serono, Flexion Therapeutics Inc., Gilead, GlaxoSmithKline, IBSA Institut Biochimique SA, Kolon TissueGene, Novartis Pharma AG, Noven Pharmaceuticals Inc., Pfizer Inc., Propella Therapeutics Inc., Regenosine, Samumed LLC and Theralogix LLC; is a member of Data Safety Monitoring Committees for clinical trials conducted by ACI Clinical, Covance Inc., Galapagos, ICON plc, and IQVIA; received royalties from Elsevier (Editor, Rheumatology 7e and Editor-in-Chief, Seminars in Arthritis and Rheumatism) and Wolters Kluwer (UpToDate^TM); and has stock ownership in BriOri Biotech and Theralogix LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.