Apremilast Achieves Statistical Significance for the Primary Endpoint of the First Phase III Study (PALACE-1) in Patients with Psoriatic Arthritis

Apremilast Achieves Statistical Significance for the Primary Endpoint of the First Phase III Study (PALACE-1) in Patients with Psoriatic Arthritis
Apremilast achieves clinically meaningful and statistically significant improvement in measures of both signs and symptoms and physical function

BOUDRY, Switzerland, Jul 12, 2012 (BUSINESS WIRE) -- --Safety is consistent with previous studies and tolerability improved over phase II program

--Celgene targets first apremilast NDA filing in the first half of 2013

--Update on comprehensive global apremilast clinical program

Celgene International Sarl, a subsidiary of Celgene Corporation today announced top-line results from the PALACE-1 study, the first of three pivotal phase III, randomized, placebo-controlled studies evaluating the Company's novel, oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients with psoriatic arthritis who had received an oral disease-modifying antirheumatic drug (DMARD), biologic therapy or had failed on an anti-tumor necrosis factor (TNF) agent. Apremilast treatment in this study was used alone or in combination with an oral DMARD.

In the study, statistical significance for the primary endpoint of ACR20 was achieved for patients receiving apremilast. Patients in the active treatment arms also maintained significant improvements in arthritis-related endpoints, including ACR50 and ACR70 through week 24. Significant and sustained improvements in various measures of physical function were also observed in apremilast-treated patients.

The overall safety profile was consistent with previous experiences in the phase II program and tolerability was improved. Common side effects for PDE4 inhibitors have been gastrointestinal in nature. In the PALACE-1 study, gastrointestinal adverse events, upper respiratory tract infections, as well as headache, were no more common in apremilast-treated patients than in those receiving placebo.

The PALACE-1 study is ongoing and the study extension remains blinded until all patients complete week 52. Full data from this phase III study will be submitted for presentation at appropriate medical meetings.

Top-line results from two pivotal randomized, placebo-controlled phase III studies of apremilast in PsA (PALACE 2 and PALACE 3) are expected in the third quarter of 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).

The NDA submission, 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.

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.

In rheumatoid arthritis, RA-002, a phase II pilot study of apremilast in combination with methotrexate did not achieve its primary endpoint of ACR20. Additional analyses from this combination therapy study are ongoing, including the potential dampening effect of methotrexate on apremilast efficacy. Data from a second phase II pilot RA study, using apremilast as monotherapy, are expected in the third quarter of 2012. Data from both of these studies will guide the registration study design by the end of this year.

About PALACE 1

PALACE-1 is one of three pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with 2 active-treatment groups. Approximately 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 primary endpoint of the study is the proportion of patients in each treatment group who achieved the American College of Rheumatology 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.

About Apremilast

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-a, IL-23, and other inflammatory cytokines. Elevation of cAMP also increases 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 Europe are affected by this arthritic condition. Up to 30 percent of people with psoriasis eventually develop psoriatic arthritis, which involves joint inflammation and can lead to joint destruction. In addition to psoriatic skin lesions, common symptoms of psoriatic arthritis include pain, stiffness and swelling in several to many joints, as well as the spine. Patients often experience psoriasis on average for 10 years before the onset of joint symptoms, and many psoriatic arthritis patients go undiagnosed.

About Celgene International Sarl

Celgene International Sarl, located in Boudry, in the Canton of Neuchatel, Switzerland, is a wholly owned subsidiary and international headquarters of Celgene Corporation. Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global pharmaceutical company engaged primarily in the discovery, development and commercialization of innovative therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit the Company's website at www.celgene.com .

Forward-Looking Statements

This press release contains forward-looking statements, which are generally statements that are not historical facts. Forward-looking statements can be identified by the words "expects," "anticipates," "believes," "intends," "estimates," "plans," "will," "outlook" and similar expressions. Forward-looking statements are based on management's current plans, estimates, assumptions and projections, and speak only as of the date they are made. We undertake no obligation to update any forward-looking statement in light of new information or future events, except as otherwise required by law. Forward-looking statements involve inherent risks and uncertainties, most of which are difficult to predict and are generally beyond our control. Actual results or outcomes may differ materially from those implied by the forward-looking statements as a result of the impact of a number of factors, many of which are discussed in more detail in our Annual Report on Form 10-K and our other reports filed with the Securities and Exchange Commission.

SOURCE: Celgene International Sarl


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