Celgene Corporation (NASDAQ: CELG) announced that updated results of a phase II, multi-center, randomized, double-blind, placebo-controlled, three-arm study of apremilast in adult patients with psoriatic arthritis (CC-10004-PSA-001) were presented today at the American College of Rheumatology (ACR) 2009 annual meeting in Philadelphia, PA.
Apremilast is an oral pluripotent immunomodulator that inhibits the activity of PDE4 and modulates the production of multiple pro-inflammatory mediators, including TNF-α, IL-2 IL-10, IL-17, and IL-23.
CC-10004-PSA-001 sought to determine the efficacy and safety of apremilast in 204 patients at two different dosing regimens - 20mg twice per day (BID) or 40mg once per day (QD) compared to placebo after 12 weeks, with 126 patients participating in an extension of the study for an additional 12 weeks (24 weeks total). Approximately 60 patients did not have the opportunity to participate in the extension due to the timing of its initiation. The extension included 40 patients that had previously received placebo and were randomized to receive one of the two dose regimens of apremilast. For patients who entered the extension, the ACR20 was 40.0% and 39.1% for 20mg BID and 40mg QD of apremilast, respectively, at 24 weeks. Additionally, subjects that switched from placebo to apremilast in the 12-week extension achieved an ACR20 of 35.0% and 40.0% in the 20mg BID and 40mg QD arms, respectively at 24 weeks.
Earlier in the year, the core (12 week) phase of PSA-001 demonstrated that 43.5% of patients in the 20mg BID (p<0.0001) and 35.8% of patients in the 40mg QD daily arm>
The ACR20 criteria measure a 20% improvement in tender and swollen joint counts, as well as pain, physical function, an inflammation laboratory marker and overall disease activity. ACR20 is the primary assessment used by the U.S. Food and Drug Administration for assessment of efficacy in psoriatic arthritis, as well as in rheumatoid arthritis.
“We are encouraged by the results of this Phase II study,” said Georg Schett, Chief of Rheumatology, Professor of Medicine at the University of Erlangen-Nuremberg and lead German investigator in the study. “In particular, the results of the 12-week extension demonstrate that improvement in the signs and symptoms of psoriatic arthritis were maintained after 24 weeks. Based on these results, we look forward to the larger, pivotal studies including higher doses to characterize the efficacy and safety of oral apremilast in this critical inflammatory disease.”
Based on evaluation of ongoing trials, pivotal phase III studies will include doses of 20mg twice per day, as well as 30 mg twice per day, to optimize the therapeutic potential of apremilast. As announced in February 2008, this dosing schedule is also being investigated in a phase IIb study in moderate-to-severe plaque-type psoriasis with results expected in the first half of 2010.
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