The FDA has approved the first extended-release, intra-articular injection for osteoarthritis knee pain. Ttriamcinolone acetonide extended-release injectable suspension (Zilretta, Flexion Therapeutics, Inc.) is a nonopioid medicine that provides pain relief over 12 weeks.
Zilretta employs proprietary microsphere technology combining triamcinolone acetonide, a commonly administered, short-acting corticosteroid, with a poly lactic-co-glycolic acid matrix. The medication is not intended for repeat administration.
The FDA approval of Zilretta is based on data from Flexion’s pivotal phase 3, randomized, double-blind clinical trial that enrolled patients at 37 centers worldwide. A total of 484 patients (Zilretta 32 mg, n = 161; placebo [saline], n = 162; active control [a crystalline suspension, immediate-release formulation of triamcinolone acetonide 40 mg], n=161) were treated and followed for up to 24 weeks. The primary efficacy endpoint comparing Zilretta to placebo was change from baseline at week 12 in the weekly mean of the average daily pain intensity scores (ADP) as assessed by a 0–10 numeric rating scale.
Zilretta demonstrated a statistically significant reduction in pain intensity at the primary endpoint versus placebo. Zilretta also demonstrated a reduction in pain intensity scores each week from weeks 1 through 12. In a secondary exploratory analysis, statistical significance was not demonstrated between Zilretta and the active control (immediate-release triamcinolone acetonide) for the change from baseline at week 12 in weekly mean ADP.
Zilretta’s label also includes the results from a double-blind, randomized, parallel-group trial that examined blood glucose concentrations in patients with type-2 diabetes. The trial demonstrated that Zilretta may avoid the disruptive blood glucose spikes that can be seen with corticosteroid use in patients coping with both knee OA and type-2 diabetes.
Sources: Flexion Therapeutics, Inc.; October 6, 2016; Zilretta Prescribing Information; October 2017.