Celgene Corporation
Oct 28, 2013
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Oral Apremilast Demonstrated Clinically Meaningful and Statistically Significant Improvements in Enthesitis and Dactylitis

At week 52, median percent improvement in swollen joint counts reached up to an 87.5% reduction and median percent improvement in tender joint count reached up to a 70.0% reduction

Significant and clinically meaningful improvements were shown in physical function at weeks 16 and 24 and were sustained over 52 weeks

BOUDRY, Switzerland--()--Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced research findings on apremilast, the Company’s first-in-class, oral, targeted inhibitor of phosphodiesterase 4 (PDE4), based on pooled data analyses from three randomized, controlled, phase III trials in psoriatic arthritis—PALACE 1, 2 and 3—at the 2013 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) annual meeting in San Diego.

“Data from these pooled phase III trials showed that apremilast treatment significantly controlled multiple manifestations of psoriatic arthritis and suggest apremilast may provide patients who are living with painful, persistent signs and symptoms of the disease with a new long-term treatment option.”



Pre-specified analyses from PALACE 1, 2 and 3 pooled data demonstrated that treatment with apremilast in patients with pre-existing enthesitis or dactylitis, two key manifestations of psoriatic disease, resulted in statistically significant and clinically meaningful improvements in enthesitis and dactylitis scores. At week 24, mean change from baseline in the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) reached statistical significance for apremilast 30 mg twice daily (BID; -1.4 vs. -0.8 for placebo; p=0.0159), but not for apremilast 20 mg BID (-1.2; P=NS). At week 24, mean changes from baseline in dactylitis count (a count of fingers and toes with dactylitis) were -1.5 (P=NS) for apremilast 20 mg BID and -1.8 (P=0.0121) for apremilast 30 mg BID, versus -1.2 for placebo.

For those patients randomized to apremilast and completing 52 weeks of the study, the median percent change from baseline in MASES and dactylitis count were -66.7% and -100% for both apremilast treatment arms, respectively.

“Psoriatic arthritis is a serious, painful arthritic condition with signs and symptoms that can make day-to-day activities difficult and impede quality of life for many patients,” said Dafna Gladman, M.D., FRCPC, Professor of Medicine, University of Toronto. “Data from these pooled phase III trials showed that apremilast treatment significantly controlled multiple manifestations of psoriatic arthritis and suggest apremilast may provide patients who are living with painful, persistent signs and symptoms of the disease with a new long-term treatment option.”

Patients treated with apremilast achieved significant reduction in number of swollen and tender joints after 16 weeks, which was maintained over 52 weeks.

A characteristic of psoriatic arthritis is tenderness and swelling in and around the joints and places where tendons and ligaments connect to bone, which can be potentially disabling if untreated. Results from all three of the PALACE studies (PALACE 1, 2 and 3) demonstrated that the number of swollen joints and the number of tender joints were both significantly reduced in patients with psoriatic arthritis who were treated with apremilast for 16 weeks compared with placebo.

These improvements were sustained over 52 weeks of treatment. Across all three studies, for those patients randomized to apremilast and completing 52 weeks of the study, the median percent reduction in swollen joint counts reached up to 87.5% and the median percent reduction in tender joint count reached up to 70.0%.

Statistically significant and clinically meaningful improvements in physical function were demonstrated after 16 and 24 weeks of treatment with apremilast 30 mg BID and were sustained over 52 weeks.

The results of physical function analyses from the PALACE 1, 2 and 3 studies demonstrated that 16 or 24 weeks’ treatment with apremilast 30 mg BID resulted in statistically significant and clinically meaningful improvements in physical function compared with placebo, as measured by the Health Assessment Questionnaire-Disability Index (HAQ-DI; P≤0.03) and the short form health survey version 2 (SF-36 v2) Physical Functioning domain (PF; P≤0.05), in each of the three PALACE studies. Improvements were maintained or increased for those patients randomized to apremilast and completing 52 weeks of the study.

Apremilast demonstrated an acceptable safety profile, with no new safety findings, and was generally well-tolerated for up to 52 weeks. Most adverse events (AEs) were mild or moderate in severity and did not lead to discontinuation. The most common reported AEs were nausea, diarrhea, headache, upper respiratory tract infection and nasopharyngitis.

These results are from investigational studies. Apremilast is not an approved product for any indication.

The New Drug Application (NDA) and the New Drug Submission (NDS), based on the combined data from PALACE 1, 2 and 3 for psoriatic arthritis, were submitted to health authorities in the U.S. and Canada in Q1 2013 and Q2 2013, respectively. An NDA to the U.S. Food and Drug Administration for psoriasis, in addition to a combined psoriatic arthritis/psoriasis Marketing Authorization Application (MAA) in Europe, are on-track for the fourth quarter of 2013.

About PALACE Program

PALACE 1, 2, 3 and 4 are the pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. In PALACE 1, 2 and 3, approximately 1,500 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 active treatment phase up to 52 weeks followed by a long-term safety phase in which all patients are treated with apremilast. The PALACE 1, 2 and 3 studies included a wide spectrum of patients with active psoriatic arthritis, including those who had been previously treated with oral DMARDs, and/or biologic DMARDs, including patients who had previously failed a tumor necrosis factor (TNF) blocker. PALACE 3 includes a large subset of patients with significant skin involvement with psoriasis.

In PALACE 4, more than 500 DMARD-naïve patients 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 active treatment phase up to 52 weeks, followed by a long-term safety phase in which all patients are treated with apremilast.

The primary endpoint of the PALACE 1, 2 3 and 4 studies is the modified American College of Rheumatology criteria for 20 percent improvement (ACR20) at week 16. Secondary endpoints include other measures of signs and symptoms, physical function and patient-reported outcomes at weeks 16 and 24.

Taken together, the PALACE program includes the most comprehensive psoriatic arthritis program to date intended for regulatory submission.

About Apremilast

Apremilast, an oral, targeted inhibitor of phosphodiesterase 4 (PDE4), intracellularly modulates the expression of a network of pro-inflammatory and anti-inflammatory cytokines. 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. An estimated 125 million people worldwide have psoriasis, approximately 30 percent of whom may also develop psoriatic arthritis. Psoriatic arthritis is a chronic disorder with progressive and additive joint inflammation that can lead to deleterious effects on quality of life and increases work disability. In addition to psoriatic skin lesions, common signs and symptoms of psoriatic arthritis include pain, stiffness and swelling in several to many joints, as well as inflammation of the spine. Patients often experience psoriasis on average for 10 years before the onset of joint symptoms, and many psoriatic arthritis patients go undiagnosed. To learn more about psoriatic arthritis, go to www.discoverpsa.com. To learn more about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.

About Celgene

Celgene International Sàrl, located in Boudry, 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 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 Celgene Corporation’s Annual Report on Form 10-K and other reports filed with the Securities and Exchange Commission.

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