Oral Apremilast Achieves Statistical Significance for the Primary Endpoint of ACR20 in the First Phase III Study (PALACE-1) in Patients with Psoriatic Arthritis

Update: Otezla (apremilast) Now FDA Approved - March 21, 2014

Apremilast significantly improves signs and symptoms of PsA in DMARDs-failure patients, including biologic-treatment-failure patients

Apremilast monotherapy demonstrates robust improvement across primary and secondary endpoints

Highest response demonstrated in biologic-naïve patient population

No significant safety signals were observed and tolerability improved over phase II program

BOUDRY, Switzerland--(BUSINESS WIRE)--Nov 13, 2012 - Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today presented the results from PALACE-1, the Company's first Phase III study in psoriatic arthritis, at the American College of Rheumatology annual meeting in Washington, D.C.

The company previously announced statistical significance for the primary endpoint of ACR20 for patients receiving apremilast in 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 oral disease-modifying antirheumatic drugs (DMARD) and/or biologic therapy and/or had failed on an anti-tumor necrosis factor (TNF) agent. Apremilast treatment in this study was used alone or in combination with oral DMARDs. PALACE-1 is the first phase III study demonstrating statistical significance in a psoriatic arthritis patient population that included both prior biologic exposure (23.6%) and biologic failures (9.3%).

In the study, apremilast demonstrated statistically significant and higher ACR20 responses at week 16 in patients receiving either apremilast 20 or 30 mg BID monotherapy (31.5% and 50.8% respectively vs. 10.5% for placebo; P<0.05 and P‰¤0.0001), with no meaningful advantage to adding oral DMARDs to apremilast. A higher ACR20 response at week 16 was also demonstrated in biologic-naïve subjects receiving apremilast 30 mg BID monotherapy compared with placebo (59% vs. 12%; P<0.005).

“The results of this first phase III trial of apremilast are encouraging for both physicians and patients as a potentially effective and safe oral therapy for psoriatic arthritis patients,” said Arthur F. Kavanaugh, M.D., Professor of Clinical Medicine at the University of California, San Diego and Director of the Center for Innovative Therapy at the University.

Across the entire study population, statistically significant changes in reducing signs and symptoms of PsA, as measured by the primary endpoint of ACR20 at week 16, were achieved for patients receiving apremilast 30 mg BID vs. placebo (41.01% vs. 19.4%; P‰¤0.0001). This was further supported by a robust and consistent response (P‰¤0.0001) across all arthritis-related secondary endpoints, including ACR50, ACR70, DAS-28, good or moderate EULAR response achievement and CDAI at week 24. Statistically significant results were also demonstrated in measures of physical function (HAQ-DI, SF-36 physical function domain score) at week 16 (P=0.0015 and P=0.0049 respectively) and these results were maintained at week 24.

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.

These results are from an investigational phase III study. Apremilast is not approved for the treatment of psoriatic arthritis.

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-α, 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 Sàrl

Celgene International Sàrl, located in Boudry, in the Canton of Neuchâtel, 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.

 

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Posted: November 2012

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