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|Apremilast Palace Program Demonstrates Robust and Consistent Statistically Significant Clinical Benefit Across Three Pivotal Phase III Studies (PALACE-1, 2 & 3) in Psoriatic Arthritis|
To date, three pivotal phase III, randomized, placebo-controlled studies including approximately 1,500 patients (PALACE-1, 2 & 3) achieve statistical significance and clinically meaningful improvements for the primary endpoint, as well as other measures of signs and symptoms and physical function
Safety consistent with previous studies and tolerability improved over phase II program
Furthermore, significant clinical benefit demonstrated in phase II study in patients with Behcet’s disease
Patients in the active treatment arms also maintained statistically significant improvements in ACR20 through week 24. 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 overall safety profile was consistent with previous experiences in the PALACE-1 study and phase II program. Tolerability was improved over the phase II program.
The PALACE-1, 2 & 3 studies are ongoing, and the study extensions remain blinded to investigational sites until all patients complete week 52. Full data from these phase III studies will be submitted for presentation at appropriate medical meetings.
The NDA submission, based on the combined PALACE-1, 2 & 3 studies for
PsA, is expected in the first quarter of 2013. A combined MAA submission
for PsA and moderate-to-severe psoriasis in
In a Phase II trial (BCT-001) in patients with Behcet’s disease (BD), a
rare inflammatory disorder and area of high unmet medical need,
statistical significance was demonstrated for the primary endpoint of
the number of oral ulcers at day 85 between apremilast 30 mg BID and
placebo. Statistical significance and clinically meaningful responses in
other manifestations of BD were also achieved. The overall safety and
tolerability profile was consistent with previous experience in other
studies with other patient populations. Behcet’s disease is a chronic
inflammatory disorder of unknown cause characterized by recurrent oral
and genital ulcers; prevalence of BD is highest in the Eastern
These results are from investigational studies. Apremilast is not an approved product for any indication.
About PALACE-1, 2 & 3
PALACE-1, 2 & 3 are three pivotal phase III 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 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 large subset of patients with significant skin involvement with psoriasis.
The primary endpoint of the studies is the proportion of patients in
each treatment group who achieved the
Taken together, the PALACE program includes the most comprehensive
psoriatic arthritis studies to date intended for regulatory submission.
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 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).
BCT-001 is a phase 2, multi-center, randomized, placebo-controlled, double-blind, parallel-group study with two treatment arms (apremilast 30mg BID and placebo) in Behcet’s disease. The study consisted of a 90-day pre-randomization phase, a 12-week treatment phase, a 12-week extension phase and a 4-week, observational follow-up phase. A total of 111 subjects with active Behcet’s disease (BD) were randomized 1:1 to receive either apremilast 30mg BID or identically appearing placebo, stratified by gender. The primary endpoint of the study is the number of oral ulcers at day 85 (12 weeks). Because virtually all patients with BD have painful oral ulcers, this manifestation was chosen as the primary efficacy variable. Other less common manifestations of BD, including genital ulcers, skin lesions, inflammatory eye disease, involvement of the gastrointestinal, vascular, and central nervous systems, and pain from oral and genital ulcers were chosen as secondary / exploratory efficacy variables or safety measures.
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.
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 Behcet’s disease
Behcet’s disease (BD) is a chronic inflammatory disorder of unknown
cause characterized by recurrent oral and genital ulcers, multiple skin
lesions ranging from acne to vasculitic ulcerations, vascular
involvement including aneurysms and venous thrombosis, and inflammatory
disease of the eye manifesting as uveitis. Prevalence of Behcet’s
disease is highest in the
About Celgene International Sàrl
Celgene International Sàrl, located in Boudry, in the
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