Fluticasone propionate injection improves osteoarthritis knee pain over 12 weeks
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Key takeaways:
- EP-104AR met the primary endpoint of statistically significant improvement of pain, and most secondary endpoints, in patients with knee osteoarthritis.
- The drug is designed to be injected into the knee, where it distributes the corticosteroid slowly, “providing local therapeutic concentrations for up to 6 months.”
EP-104AR, an injectable form of fluticasone propionate designed slowly distribute through the knee joint and provide pain relief for up to 6 months, improved pain vs. a placebo over 12 weeks, according to the manufacturer.
Eupraxia Pharmaceuticals stated in a press release that they are developing EP-104AR (fluticasone propionate) as an injectable therapy that can deliver “long-lasting disease relief” in OA cases that would benefit from sustained corticosteroid delivery.
“To have statistically significant and clinically meaningful effects on pain, together with a compelling safety profile, supports EP-104IAR’s potential in OA,” Lee Simon, MD, a rheumatologist and former director of the FDA Analgesic, Anti-inflammatory, Ophthalmologic Drug Products division, said in the release. “EP-104IAR’s efficacy profile, durability of response, and tolerability suggest the product has the potential to be an important new therapy, compared to currently available osteoarthritis treatments.”
The phase 2b, randomized, double-blind, vehicle-controlled trial included 318 patients with knee OA across 12 sites in Denmark, Poland and the Czech Republic. Among these patients, 163 received EP-104IAR, while 155 received placebo, according to the release.
The primary endpoint was improvement in WOMAC pain scale from baseline to 12 weeks. Secondary endpoints included difference in change from baseline in the WOMAC Function subscale, the difference in the area under the curve (AUC) of the WOMAC Pain subscale, and the difference in Outcome Measures in Rheumatology-Osteoarthritis Research Society International (OMERACT-OARSI) strict responders — at 12 weeks.
According to the press release, patients who received EP-104IAR achieved the primary endpoint with a “clinically meaningful and statistically significant” improvement in WOMAC Pain vs. placebo at 12 weeks (P = .004). The therapy additionally demonstrated statistically significant improvement over placebo at 12 weeks in three of four secondary endpoints — WOMAC function (P = .014), OMERACT-OARSI strict responders (P = .011), and AUC for WOMAC pain (P < .001).
Additionally, the therapy appeared to be well-tolerated. The adverse event characterization was similar between the groups that received the therapy and placebo, according to the company. There were no therapy withdrawals due to adverse events, the release said.
Eupraxia said it aims to “aggressively pursue” phase 3 development following a recent fast-track designation from the FDA.
“We are ecstatic about these results,” Eupraxia CEO James Helliwell, MD, said in the release. “Our objective from the beginning was to design a product that provides prolonged duration with a compelling safety profile that may allow for repeat and bilateral dosing. We believe these Phase 2b results move us closer towards that goal, which could potentially change the OA treatment paradigm. If approved, this represents a significant opportunity to treat millions of underserved patients. In addition, these data provide further validation of our technological platform and the potential for its use in other indications.”
Perspective
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David A. McLain, MD, MACR, FACP, FRCP
EP-104IAR is composed of fluticasone propionate (FP) drug crystals coated with heat-treated polyvinyl alcohol (PVA) to produce extended-release properties. FP is a trifluorinated glucocorticoid that is an upper mid-strength corticosteroid — based on topical classification — that has 20-fold higher affinity for the glucocorticoid receptor than triamcinolone acetonide. It is best known for its use in the former prescription branded Flonase (GlaxoSmithKline) nasal spray.
FP demonstrates greater potency than triamcinolone acetonide in suppressing human T-cell migration and proliferation. It also effectively inhibits the release of cytokines from CD4+ T cells, reduces the expression of adhesion molecules, promotes apoptosis in inflammatory cells, and triggers the release of cellular antiproteases. FP has an elimination half-life of 14.4 hours, which is considerably longer than triamcinolone (3.6 hours).
PVA is a non-toxic, colorless, odorless and biodegradable polymer that is safe to use and consume. PVA is approved by the FDA for use in food packaging and pharmaceutical applications. In animal studies, EP-104IAR displayed sustained plasma concentrations for up to 45 days and remained in synovial fluid and cartilage for up to 14 days. In humans, the PVA-coated FP microcrystals allow gradual drug release over 6 months, offering a potential advancement in knee osteoarthritis treatment.
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