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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