ABSTRACT #SAT0299; OP0104; SAT0280
The PALACE 3 study, which evaluated 495 patients, demonstrated
statistical significance in achieving the primary endpoint of
Patients in the 30 mg BID active treatment arm also demonstrated significant and sustained improvements in psoriasis-related endpoints, including Psoriasis Area Severity Index (PASI) 50 and PASI-75 at week 24. Similar improvements in 30 mg BID-treated patients were also observed in key secondary endpoints, including various measures of physical function, signs and symptoms and quality of life.
The safety and tolerability profile of apremilast in PALACE 3 was consistent with other previously reported phase III studies of the therapy in psoriatic arthritis.
Apremilast Pooled Safety Analysis Presented
The company also presented results from a pooled safety data analysis encompassing multiple randomized controlled phase III studies, PALACE 1, 2 & 3.
In the 24-week placebo-controlled analysis, which included nearly 1,500 patients from the three phase III studies, the most common AEs (≥5%) were diarrhea, nausea, headache and URTI. The majority of AEs (93-96%) were mild or moderate in severity, with discontinuation rates due to AEs (PBO, 4.2%; apremilast 20 mg BID, 5.6%; apremilast 30 mg BID, 7.2%). Serious AEs occurred in 3.8%, 3.4% and 3.8% of PBO, apremilast 20 mg BID and apremilast 30 mg BID, respectively. Importantly, there were no safety signals with respect to major cardiac events, malignancies, including lymphoma or systemic opportunistic infections, and no cases of reactivations of tuberculosis.
These results are from investigational studies. Apremilast is not an approved product for any indication.
The NDA/NDS submissions, based on the combined data from PALACE 1, 2 & 3
for PsA, were submitted to health authorities in the U.S. and
About PALACE Program
PALACE 1, 2, 3 & 4 are four pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. In PALACE 1, 2 & 3, approximately 1,500 subjects were randomized 1:1:1 to receive either apremilast 20 mg BID, 30 mg BID, 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 DMARD, biologic DMARD, as well as patients who had previously failed a TNF blocker. PALACE-3 includes a subset of 270 patients with significant skin involvement with psoriasis.
The primary endpoint of the PALACE 1, 2 & 3 studies is the proportion of
patients in each treatment group who achieved the
In PALACE 4, more than 500 DMARD-naïve patients were randomized 1:1:1 to receive either apremilast 20 mg BID, 30 mg BID, or identically-appearing placebo for 24 weeks, with a subsequent extension in which all patients are treated with apremilast.
Taken together, the PALACE program includes the most comprehensive
psoriatic arthritis studies to date intended for regulatory submission.
Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4), intracellularly modulates 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 anti-inflammatory cytokines such as IL-10.
About Psoriatic Arthritis
Psoriatic arthritis is a painful, chronic inflammatory disease
associated with the skin condition psoriasis. More than a million people
in the U.S. and
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