In the study, statistical significance for the primary endpoint of ACR20 was achieved for patients receiving apremilast. Patients in the active treatment arms also maintained significant improvements in arthritis-related endpoints, including ACR50 and ACR70 through week 24. Significant and sustained improvements in various measures of physical function were also observed in apremilast-treated patients.
The overall safety profile was consistent with previous experiences in the phase II program and tolerability was improved. Common side effects for PDE4 inhibitors have been gastrointestinal in nature. In the PALACE-1 study, gastrointestinal adverse events, upper respiratory tract infections, as well as headache, were no more common in apremilast-treated patients than in those receiving placebo.
The PALACE-1 study is ongoing and the study extension remains blinded until all patients complete week 52. Full data from this phase III study will be submitted for presentation at appropriate medical meetings.
Top-line results from two pivotal randomized, placebo-controlled phase
III studies of apremilast in PsA (PALACE 2 and PALACE 3) are expected in
the third quarter of 2012. Taken together, the PALACE program is
comprised of the most comprehensive psoriatic arthritis studies to date
intended for regulatory submission. Results from
In addition, two large, pivotal global studies of apremilast in more than 1,200 patients with moderate-to-severe psoriasis (ESTEEM 1 and 2) are ongoing with data expected beginning by the end of this year. Results from PSOR-005, a phase IIb dose-range study, were recently published in The Lancet (http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(12)60642-4/fulltext).
The NDA submission, based on the combined PALACE program for PsA, is
expected in the first half of 2013. The sNDA submission for psoriasis is
expected to follow in the second half of 2013. A combined MAA submission
A randomized, placebo-controlled phase III study (POSTURE) of apremilast
in ankylosing spondylitis (AS) began enrolling patients in
In rheumatoid arthritis, RA-002, a phase II pilot study of apremilast in combination with methotrexate did not achieve its primary endpoint of ACR20. Additional analyses from this combination therapy study are ongoing, including the potential dampening effect of methotrexate on apremilast efficacy. Data from a second phase II pilot RA study, using apremilast as monotherapy, are expected in the third quarter of 2012. Data from both of these studies will guide the registration study design by the end of this year.
About PALACE 1
PALACE-1 is one of three pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with 2 active-treatment groups. Approximately 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 primary endpoint of the study is the proportion of patients in each
treatment group who achieved the
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 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
About Celgene International Sàrl
Celgene International Sàrl, located in Boudry, in the
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