Levicept Ltd announced positive results from its Phase II clinical trial of LEVI-04, a novel neurotrophin-3 (NT-3) inhibitor, for the treatment of moderate to severe osteoarthritis. The data, presented at the American College of Rheumatology's ACR Convergence 2024, demonstrated significant pain relief and improved function in patients with osteoarthritis of the knee.
The multi-arm, multi-center, randomized, double-blind, placebo-controlled study (NCT05618782) enrolled 518 participants. LEVI-04, a p75 neurotrophin receptor fusion protein (p75NTR-Fc), works by inhibiting NT-3 activity, modulating excess neurotrophin levels in osteoarthritic joints.
Significant Pain Reduction Achieved
The trial met its primary efficacy endpoint, with all doses of LEVI-04 (0.3mg/kg, 1mg/kg, 2mg/kg) showing statistically significant differences compared to placebo in the WOMAC pain assessment (change from baseline at Week 17) (p<0.05). The mean reduction in WOMAC pain score from baseline was greater than 50% for all three doses. More than 50% of LEVI-04-treated patients reported ≥50% reduction in pain, and over 35% reported ≥70% reduction at week 17.
Improvements in Function and Stiffness
Secondary endpoints, including WOMAC subscales for function and joint stiffness, patient global assessment, and daily pain scores, also showed statistically significant improvements compared to placebo.
Favorable Safety Profile
LEVI-04 was well-tolerated, with no increased incidence of serious adverse events (SAEs), treatment-emergent adverse events (TEAEs), or joint pathologies, including rapidly progressive osteoarthritis, compared to placebo. This was determined via detailed radiographic analysis.
Expert Commentary
Professor Philip Conaghan, Director NIHR Leeds Biomedical Research Centre and Principal Investigator, stated, "We believe these are truly exceptional results from a robust and well-designed study. LEVI-04 demonstrated significant and clinically meaningful improvement in pain, function and other outcomes and was well tolerated at all doses studied."
He further emphasized the need for safer and more effective pain management options in osteoarthritis, noting the limitations of existing treatments due to adverse effects, addiction liabilities, and poor efficacy. "These results support the concept of supplementing endogenous p75NTR as a treatment for osteoarthritis, and our belief that LEVI-04 has the potential to offer a vital new treatment option to millions of patients in need."
Future Directions
Eliot Forster, CEO of Levicept, expressed confidence in LEVI-04's potential as a breakthrough treatment for osteoarthritis and indicated the company's focus on strategic options to advance its development.
