Philip Conaghan, MBBS, PhD: Investigating NT3 Inhibition for Improving Osteoarthritis

LEVI-04 (Levicept), a first-in-class neurotrophin-3 (NT3) inhibitor, was well-tolerated and significantly and meaningfully improved pain, function, and other outcomes in people with osteoarthritis (OA).

Data from the phase 2 trial evaluating LEVI-04 were presented at the American College of Rheumatology (ACR) Convergence 2024, held November 14-19 in Washington, DC, by Philip Conaghan, MBBS, PhD, director, National Institute for Health & Care Research Leeds Biomedical Research Centre, and professor, Musculoskeletal Medicine, University of Leeds.

“We think NT3 could be a relevant target, and this will move beyond osteoarthritis pain. There are many musculoskeletal conditions associated with pain, [and] there's real reason to believe this drug could be useful for other sources of peripherally driven pain. So, I think this is a pretty exciting time for pain and for rheumatologists who look at musculoskeletal disease,” Conaghan told HCPLive® while onsite at the meeting.

All doses evaluated in the trial met statistical significance on primary and secondary endpoints at weeks 5 and 17 (P <.05). Over half of patients treated with LEVI-04 had at least a 50% reduction in pain and over 25% had at least a 75% reduction in pain at weeks 5 and 17 on a covariate-adjusted ANCOVA model with Dunnett’s step-down testing procedure comparing active arms with placebo. There were no increased incidence of serious adverse events (AEs), treatment-emergent AEs, and joint pathologies, including rapidly progressive OA, compared with placebo.

Conaghan’s relevant disclosures include Eli Lilly, Eupraxia, Formation Bio. Genascence, GlaxoSmithKlein, Grunenthal, Janssen, Kolon TissueGene, Levicept, Medipost, Moebius, Novartis, Pacira, Sandoz, Stryker, and Takeda.

REFERENCE

Conaghan P, Guermazi A, Katz N, et al. LEVI-04, a Novel neurotrophin-3 Inhibitor, Substantially Improves Pain and Function Without Deleterious Effects on Joint Structure in People with Knee Osteoarthritis: A Randomized Controlled Phase II Trial. Presented at: ACR Convergence 2024; November 14-19; Washington, DC. Abstract L15