FDA Accepts LEVI-04 IND, Potential Targeted Osteoarthritis Therapy

The United States Food and Drug Administration (US FDA) has accepted Levicept’s investigational new drug application (IND) for the company’s investigational LEVI-04 therapy for osteoarthritis (OA).¹

“This new IND is an important step in our further development of LEVI-04 with the potential to treat millions of OA patients in need worldwide. We have already demonstrated LEVI-04 has a unique profile in its potential to significantly reduce pain and also directly address the disease process. We look forward to the next steps in our clinical program and further building the data package around this important molecule,” Eliot Forster, CEO of Levicept, said in a statement.¹

LEVI-04 has been evaluated in a multicenter, randomized, placebo-controlled phase 2 study in 518 participants with pain and disability due to knee OA. These findings were presented by Philip Conaghan, MBBS, PhD, Director, NIHR Leeds Biomedical Research Centre, and Professor of Musculoskeletal Medicine at University of Leeds at the American College of Rheumatology (ACR) Convergence 2025, held October 24–29 in Chicago, Illinois.

Participants were randomized to receive intravenous placebo or LEVI-04 at doses of 0.3, 1.0, or 2.0 mg/kg at baseline and every 4 weeks through week 16. The primary endpoint was change in WOMAC pain at week 17, with additional assessments of WOMAC function, stiffness, patient global assessment (PGA), and average weekly numerical rating scale (NRS) pain.

Across all doses, LEVI-04 achieved statistically significant improvements in WOMAC pain versus placebo, with effect sizes that met or exceeded those typically reported for NSAIDs, in a dose-dependent manner. Following 20 weeks of treatment, significantly fewer participants with LEVI-04 1 mg/kg (46%) and 2 mg/kg (39%) had bone marrow lesions, compared with no change in the placebo group (72%). Clinical meaningfulness was further supported by results from the Staircase-Evoked Pain Procedure (StEPP), a standardized measure of pain on movement. A greater proportion of participants treated with LEVI-04 achieved the minimum clinically important difference (MCID) of 2 points in the StEPP versus placebo, with statistical significance observed in the 1.0 and 2.0 mg/kg groups.

LEVI-04 is a first-in-class p75 neurotrophin receptor-Fc fusion protein and potential disease modifying therapy for OA. Levicept is planning phase 3 studies to confirm the efficacy and safety of LEVI-04 and further evaluate its long-term impact on pain and functional outcomes in a broader participant population and to allow further data gathering on long-term dosing.

"What we see that more people on LEVI-04 for all 3 doses achieved a clinically relevant reduction in that step function. So in other words, they were able to do more steps. Their pain related to steps was reduced, and that's really important for osteoarthritis, which is a disease where all the pain is related to how much you walk," Conaghan told HCPLive.

References

1. Levicept Announces FDA Acceptance of IND Application for LEVI-04, a Potentially Disease-Modifying Treatment for Osteoarthritis. News release. Levicept. January 20, 2026. https://www.globenewswire.com/news-release/2026/01/20/3221340/0/en/Levicept-Announces-FDA-Acceptance-of-IND-Application-for-LEVI-04-a-Potentially-Disease-Modifying-Treatment-for-Osteoarthritis.html

2. Conaghan P, Katz N, Bihlet A, et al. LEVI-04, a Novel Neurotrophin-3 Inhibitor, Demonstrates Clinically Meaningful Improvements in Pain and Physical Function across a Range of OA Outcomes, Including the Staircase-Evoked Pain Procedure (StEPP). Presented at: ACR Convergence 2025; October 24-29; Chicago, Illinois. Poster #2101