SAN DIEGO — A novel extended-release formulation of fluticasone propionate provided long-lasting symptom improvement with a single injection in patients with knee osteoarthritis (OA), according to a phase II study presented here.
Called EP-104IAR, the product was substantially more effective than placebo in reducing pain as assessed via the Western Ontario McMaster Universities Arthritis Index (WOMAC) over more than 3 months, reported James Helliwell, MD, CEO of Eupraxia Pharmaceuticals in Victoria, British Columbia, and colleagues.
Response rates with the product topped 50% through week 14 after the intra-articular injection, whereas no more than 40% of the randomized trial’s placebo group was ever classified as a responder, according to the group’s report at the American College of Rheumatology annual meeting.
This duration of response was longer than what all currently approved drugs including immediate and extended-release corticosteroids are able to provide after one dose, the researchers boasted.
EP-104IAR uses a proprietary polymer coating technology to release fluticasone within the joint slowly over a period of weeks, thus prolonging the active lifetime of a single injection.
Helliwell and colleagues enrolled 318 patients with moderate-to-severe knee OA in three European countries (Denmark, Poland, and Czech Republic) for the double-blind trial, randomizing them in equal numbers to the novel fluticasone product at 25 mg or placebo delivered by intra-articular injection. WOMAC pain score tracked through month 6 was the primary outcome measure; the proportion of patients achieving at least 50% improvement in pain by OARSI-OMERACT criteria was the key secondary endpoint.
WOMAC pain scores decreased in both treatment arms but more so with EP-104IAR: in the first week after dosing, mean scores fell 2.5 points from baseline in the active-drug group versus 1.6 points with placebo. By week 6, the decline from baseline surpassed 3 points with EP-104IAR. Pain continued to diminish slowly in the placebo group, but remained greater than in the intervention arm until week 18.
Improvement of 50% was achieved by 45% of those on EP-104IAR in the first week and hit 50% on week 2, remaining near that level through week 14. Throughout the entire 6 months of follow-up, the response rate with placebo never matched that of EP-104IAR.
Helliwell’s group also examined treatment effects in the subgroup of patients with non-severe OA, who comprised about two-thirds of the entire sample. The proportion of patients achieving WOMAC scores of 1 or less — amounting to near-remission of knee pain — reached about 30% with the active drug, versus less than 10% in those receiving placebo.
Adverse event rates were similar in the two arms. Although four patients on EP-104IAR had serious treatment-emergent events, versus one in the placebo group, Helliwell and colleagues determined that none were drug-related. Two patients receiving the active drug withdrew from the study because of new adverse events, but these too were classified as non-drug related. Indeed, prior to beginning clinical development, Eupraxia had considered whether the long-term presence of fluticasone within the joint might damage cartilage, but animal studies alleviated this concern. Overall, no significant safety signals emerged from the trial.
Eupraxia plans to begin phase III testing with EP-104IAR; it is also developing other formulations of polymer-coated fluticasone for eosinophilic esophagitis (now in phase II testing) and perhaps additional indications.
The trial was funded by Eupraxia Pharmaceuticals.
Most authors including Helliwell were company employees.
American College of Rheumatology
Source Reference: Helliwell J, et al “EP-1041AR (extended-release fluticasone propionate for injectable suspension): topline and key secondary results from a phase 2 randomized, double-blind, vehicle-controlled trial in subjects with knee osteoarthritis” ACR 2023; Abstract L04.