Phase 3 Trial Update of Apremilast for Psoriatic Arthritis
Celgene announced that statistical significance for the primary endpoint (the proportion of patients in each treatment group who achieved the American College of Rheumatology criteria for 20% improvement [ACR20] compared to baseline at Week 16) was achieved for psoriatic arthritis patients receiving apremilast 20mg and 30mg twice daily in both the PALACE-2 & 3 Phase 3 studies.
PALACE-1, 2 & 3 are three pivotal Phase 3 multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. Approximately 1,500 subjects were randomized 1:1:1 to receive either apremilast 20mg twice daily, 30mg twice daily, or identically-appearing placebo for 24 weeks, with a subsequent extension in which all patients are treated with apremilast. The three PALACE studies included a wide spectrum of patients with active psoriatic arthritis, including those who had been previously treated with oral disease-modifying antirheumatic drugs (DMARDs), biologic DMARDs, as well as patients who had previously failed a tumor necrosis factor (TNF) blocker. In each of these studies, apremilast was used alone or in combination with oral DMARDs. PALACE-3 includes a large subset of patients with significant skin involvement with psoriasis. Secondary endpoints include other measures of signs and symptoms, physical function and patient-reported outcomes.
Patients in the active treatment arms also maintained statistically significant improvements in ACR20 through Week 24. Positive PALACE-1 data was previously reported. Consistent with PALACE-1, statistically significant and clinically meaningful responses in various measures of signs and symptoms and physical function were also observed in both studies in apremilast-treated patients through Week 24.
The PALACE-1, 2 & 3 studies are ongoing, and the study extensions remain blinded to investigational sites until all patients complete Week 52. An NDA submission, based on the combined PALACE-1, 2 & 3 studies for PsA, is expected in the first quarter of 2013.
Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4), works intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory cells. PDE4 inhibition elevates intracellular cAMP levels, which in turn down-regulates the inflammatory response by modulating the expression of TNF-α, IL-23, and other inflammatory cytokines. Elevation of cAMP also increases other anti-inflammatory cytokines such as IL-10.
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