Updated Data from Randomized Controlled Phase II Study Evaluating Oral Apremilast in Psoriatic Arthritis Demonstrates Sustained Response at Six Months
Study Extension Demonstrates ACR20 of 40% and 39% for 20mg BID and 40mg QD of Apremilast, Respectively, at 24 Weeks
Activity and Safety Profile Supports Initiation of Pivotal Phase III Studies in the First Half of 2010
SUMMIT, N.J.--(BUSINESS WIRE)--Oct 19, 2009 - 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-Î±, 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 (p=0.002), respectively, achieved an ACR20 compared to 11.8% of patients taking placebo.
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.
PSA-001 also assessed secondary 12-week endpoints including ACR50 and ACR70, defined as the percentage of patients achieving 50% and 70% improvements, respectively, according to ACR criteria. These measures are used to demonstrate additional clinical benefit to patients in addition to the primary regulatory measure of ACR20. The 12-week ACR50 was 17.4% in the 20mg BID arm, 13.4% in the 40mg QD arm, and 2.9% in the placebo arm. The 12-week ACR70 was 5.8% in the 20mg BID arm, 7.5% in the 40mg QD arm, and 1.5% in the placebo arm. In patients who received apremilast who continued into the 12-week extension, the 24-week ACR50 was 20.0% in the 20mg BID arm, and 23.9% in the 40mg QD arm. The 24-week ACR70 was 15.0% in the 20mg BID arm, and 13.0% in the 40mg QD arm.
The most common adverse events (AEs) were transient nausea, diarrhea, headache, nasopharyngitis, and fatigue. Discontinuations due to AEs were 9% and 6% of apremilast subjects (20 mg BID, 40 mg QD, respectively), vs 3% in the placebo group. Discontinuations due to lack of efficacy were 7% and 0% of apremilast subjects (20 mg BID, 40 mg QD, respectively), vs 15% in the placebo group. Eight subjects had a serious AE (SAE) during the 12 week study period (four in 20 mg BID, zero in 40 mg QD, four in placebo patients); seven subjects reported an SAE in the extension. There was no obvious difference in infections between the apremilast and placebo groups and there were no deaths during the study.
Psoriatic arthritis is a type of inflammatory arthritis that affects more than a million people in the U.S. and Europe. This debilitating condition causes pain, stiffness and swelling in and around the joints, as well as joint destruction.
Apremilast is a novel, oral pluripotent immunomodulator that exhibits anti- inflammatory activities through the modulation of multiple pro-inflammatory mediators through PDE4 inhibition. Targeted inflammatory mediators and cell types affected by the pluripotent mechanism of action of apremilast include: inhibition of production of TNF-a, IFN-g, IL-12, IL-23, IL-2, IL-5, IL-17, CXCL9 (MIG), CXCL10 (IP-10), CCL2 (MCP-1), CCL3 (MIP-1a), IL-8, LTB4, and iNOS; inhibition of activation of T and NK cells, monocytes, dendritic cells, synovial macrophages, neutrophils, chondrocytes, keratinocytes, and endothelial cells; as well as, the unique inhibition of joint pannus formation and cartilage erosion. Apremilast is the lead investigational anti-inflammatory compound in the Celgene Immunology and Inflammation Franchise, and is in phase II clinical development for the treatment of moderate to severe psoriasis, psoriatic arthritis and in proof of concept trials in other debilitating inflammatory diseases.
About Celgene Corporation
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the company's Web site at www.celgene.com.
This release contains certain forward-looking statements which involve known and unknown risks, delays, uncertainties and other factors not under the Company's control, which may cause actual results, performance or achievements of the Company to be materially different from the results, performance or other expectations implied by these forward-looking statements. These factors include results of current or pending research and development activities, actions by the FDA and other regulatory authorities, and those factors detailed in the Company's filings with the Securities and Exchange Commission such as Form 10-K, 10-Q and 8-K reports.
Contact: Celgene Corporation
David Gryska, 908-673-9059
Sr. Vice President and
Chief Financial Officer
Brian P. Gill, 908-673-9530
Posted: October 2009