Celgene has announced that statistical significance for the primary endpoint of ACR20 at week 16 was achieved for patients receiving Apremilast 20 mg and 30 mg BID in both the PALACE-2 & 3 phase III studies.
PALACE-1, PALACE-2 and 3 are three pivotal phase III, randomized, placebo-controlled studies evaluating oral small-molecule inhibitor of phosphodiesterase 4 ( PDE-4 ) in patients with psoriatic arthritis who had received or failed oral disease-modifying antirheumatic drugs ( DMARDs ), and/or an anti-tumor necrosis factor ( TNF ) agent. In each of these studies, Apremilast was used alone or in combination with oral DMARDs.
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 and 3 studies are ongoing, and the study extensions remain blinded to investigational sites until all patients complete week 52.
In a Phase II trial ( BCT-001 ) in patients with Behcets disease 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 Behcets disease were also achieved.
The overall safety and tolerability profile was consistent with previous experience in other studies with other patient populations.
Behcets disease is a chronic inflammatory disorder of unknown cause characterized by recurrent oral and genital ulcers; prevalence of Behcets disease is highest in the Eastern Mediterranean, the Middle East and East Asia, but is classified as an orphan disease by the NIH ( National Institutes of Health ) in the United States and EURODIS in Europe.
Apremilast 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-alpha, IL-23, and other inflammatory cytokines. Elevation of cAMP also increases other anti-inflammatory cytokines such as IL-10.
About PALACE-1, 2 and 3
PALACE-1, 2 and 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 American College of Rheumatology ( ACR ) criteria for 20% improvement ( ACR20 ) compared to baseline at week 16. Secondary endpoints include other measures of signs and symptoms, physical function and patient-reported outcomes.
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 Behcets 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 Behcets disease 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 Behcets disease have painful oral ulcers, this manifestation was chosen as the primary efficacy variable. Other less common manifestations of Behcets disease, 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.
Source: Celgene, 2012