EP-104IAR Phase 2 Data Shows Potential for Knee Osteoarthritis Pain

James Helliwell, MD

Credit: Eupraxia

EP-104IAR seems to be safe and efficacious in reducing pain in people with knee osteoarthritis (OA) for up to 14 weeks, according to data from a phase 2 trial.¹

"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," James Helliwell, MD, cofounder and CEO, Eupraxia, said in a statement.² "As outlined in the publication, EP-104IAR imparts clinically significant and durable pain relief, while also having minimal changes in glucose and cortisol, along with stable fluticasone proportionate concentrations in plasma. We continue to evaluate multiple program advancement strategies for this exciting and highly differentiated Phase 3-ready clinical asset that we believe holds the potential to advance the standard of care for individuals suffering from knee osteoarthritis."

The findings reported were from the phase 2 randomized, vehicle-controlled, double-blind SPRINGBOARD trial (NCT04120402) done at 12 research sites in Denmark, Poland, and Czech Republic that evaluated 104IAR, a diffusion-based extended-release fluticasone propionate intra-articular injection.

Helliwell and colleagues analyzed data from 318 participants aged 40 years or older screened between September 2021 and November 2022 with primary knee OA randomly assigned to EP-104IAR (n=163) or vehicle control (n=155). Participants were mostly female (n = 183; 58%) and largely white (n = 315; 99%).¹

The investigators found that at week 12, least squares mean change in Western Ontario and McMaster Universities Osteoarthritis Arthritis Index (WOMAC) pain score from baseline was –2·89 (95% CI, –3·22 to –2·56) in the EP-104IAR group and –2·23 (95% CI, –2·56 to –1·89) in the vehicle control group, with a between-group difference of –0·66 (95% CI, –1·11 to –0·21; P = ·0044). The between-group difference remained significant until week 14 and these data satisfied the primary outcome of the SPRINGBOARD trial.¹

Rates of treatment-emergent AEs were similar between groups, with 65% (n = 106) of the EP-104IAR group and 57% (n = 89) of the control vehicle group experiencing at least 1 treatment-emergent AE. Treatment-related arthralgia was similar between the EP-104IAR group (n = 9 participants; 6%) and vehicle control (n = 9 participants; 6%). There were no treatment-emergent deaths or treatment-related serious AEs and the effects on serum glucose and cortisol concentrations were minimal and transient. The investigators noted that plasma concentrations of fluticasone propionate had a blunted initial peak with a terminal half-life of approximately 18–20 weeks.¹

"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," senior investigator Philip Conaghan, Professor of Musculoskeletal Medicine, University of Leeds, added to the statement.² "Based on the data from this Phase 2 study, I look forward to seeing this product candidate continue to advance into late-stage, pivotal testing."

REFERENCES

1. Malone A, Kowalski MM, Helliwell J, et al. Efficacy and safety of a diffusion-based extended-release fluticasone propionate intra-articular injection (EP-104IAR) in knee osteoarthritis (SPRINGBOARD): a 24-week, multicentre, randomised, double-blind, vehicle-controlled, phase 2 trial. Lancet Rheumatol. Published online October 11, 2024. doi: 10.1016/S2665-9913(24)00223-6

2. Lancet Rheumatology Publishes Phase 2b Data on Eupraxia Pharmaceuticals' EP-104IAR for the Treatment of Knee Osteoarthritis. News release. Eupraxia Pharmaceuticals. October 15, 2024. https://finance.yahoo.com/news/lancet-rheumatology-publishes-phase-2b-110000307.html