The overall safety profile was consistent with previous experiences in the phase II program. Importantly, no opportunistic infections (including TB) or lymphoma were observed through week 24, and there was no increase in risk of cardiovascular events. Apremilast was generally well tolerated. The majority of AEs (>95%) were mild or moderate, with serious AEs and discontinuations due to AEs similar across all treatment arms.
An NDA submission to the U.S. Food and Drug Administration, 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 in Europe is also planned for the second half of 2013.
Top-line positive results from two pivotal randomized, placebo-controlled phase III studies of apremilast in PsA (PALACE 2 and PALACE 3) were released in September 2012. Taken together, the PALACE program is comprised of the most comprehensive psoriatic arthritis studies to date intended for regulatory submission. Results from PSA-001, the phase II study of apremilast in psoriatic arthritis, were recently published online in the journal Arthritis & Rheumatism ( http://onlinelibrary.wiley.com/doi/10.1002/art.34580/abstract).
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).A randomized, placebo-controlled phase III study (POSTURE) of apremilast in ankylosing spondylitis (AS) began enrolling patients in April 2012. AS, a debilitating disease, which may cause fusion of the spine, arthritis, inflammation of the eye and damage to the heart affects approximately 1.5 million people in the U.S. and Europe. The trial will randomize approximately 450 patients to receive 20mg or 30mg apremilast, or placebo BID. The primary endpoint is the proportion of patients achieving an ASAS 20 score at week 16.