A Phase 2 trial has revealed that EP-104IAR, a diffusion-based extended-release fluticasone propionate intra-articular injection, demonstrates both safety and efficacy in alleviating pain associated with knee osteoarthritis (OA) for up to 14 weeks. The findings suggest a potential advancement in OA treatment, addressing a significant unmet need for durable pain relief.
The SPRINGBOARD trial (NCT04120402), a randomized, vehicle-controlled, double-blind study, was conducted across 12 research sites in Denmark, Poland, and the Czech Republic. The trial involved 318 participants aged 40 years or older with primary knee OA, who were randomly assigned to receive either EP-104IAR (n=163) or a vehicle control (n=155).
Efficacy and Safety Results
The primary outcome of the SPRINGBOARD trial was met, with results showing that at week 12, the least squares mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score from baseline was -2.89 (95% CI, -3.22 to -2.56) in the EP-104IAR group, compared to -2.23 (95% CI, -2.56 to -1.89) in the vehicle control group. The between-group difference was -0.66 (95% CI, -1.11 to -0.21; P = 0.0044), remaining significant until week 14.
The safety profile of EP-104IAR was comparable to the control, with 65% (n = 106) of the EP-104IAR group and 57% (n = 89) of the control vehicle group experiencing at least one treatment-emergent adverse event (AE). Treatment-related arthralgia occurred at similar rates in both groups (6%). Notably, there were no treatment-emergent deaths or treatment-related serious AEs, and the effects on serum glucose and cortisol concentrations were minimal and transient. Plasma concentrations of fluticasone propionate exhibited a blunted initial peak with a terminal half-life of approximately 18–20 weeks.
Expert Commentary
"The publication of our Phase 2b data in a distinguished and respected journal such as Lancet Rheumatology raises the profile of EP-104IAR and further underscores the potential of this product candidate to become a best-in-class therapy for the treatment of knee osteoarthritis," said James Helliwell, MD, cofounder and CEO of Eupraxia. He further noted that EP-104IAR provides clinically significant and durable pain relief with minimal changes in glucose and cortisol levels.
Senior investigator Philip Conaghan, Professor of Musculoskeletal Medicine at the University of Leeds, added, "By utilizing an advanced formulation technology, the improved pharmacokinetic and pharmacodynamic profile of EP-104IAR appears to offer strong and sustainable pain relief and shows the potential to significantly improve upon the safety profile for this drug class."
Implications for Osteoarthritis Treatment
These findings suggest that EP-104IAR could represent a significant advancement in the treatment of knee osteoarthritis, offering a balance of efficacy and safety. Further late-stage, pivotal testing is anticipated to confirm these promising results.
