Celgene Corporation
Sep 6, 2012
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Apremilast Palace Program Demonstrates Robust and Consistent Statistically Significant Clinical Benefit Across Three Pivotal Phase III Studies (PALACE-1, 2 & 3) in Psoriatic Arthritis

To date, three pivotal phase III, randomized, placebo-controlled studies including approximately 1,500 patients (PALACE-1, 2 & 3) achieve statistical significance and clinically meaningful improvements for the primary endpoint, as well as other measures of signs and symptoms and physical function

Safety consistent with previous studies and tolerability improved over phase II program

Celgene targets first apremilast NDA submission for first quarter of 2013

Furthermore, significant clinical benefit demonstrated in phase II study in patients with Behcet’s disease

BOUDRY, Switzerland--(BUSINESS WIRE)--Sep. 6, 2012-- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today announced that statistical significance for the primary endpoint of ACR20 at week 16 was achieved for patients receiving apremilast 20 mg and 30 mg BID in both the PALACE-2 & 3 phase III studies. Positive PALACE-1 data was previously reported. PALACE-2 & 3 are the second and third 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 or failed oral disease-modifying antirheumatic drugs (DMARDs), and/or an anti-tumor necrosis factor (TNF) agent. In each of these studies, apremilast was used alone or in combination with oral DMARDs.

Patients in the active treatment arms also maintained statistically significant improvements in ACR20 through week 24. Consistent with PALACE-1, statistically significant and clinically meaningful responses in various measures of signs and symptoms and physical function were also observed in both studies in apremilast-treated patients through week 24.

The overall safety profile was consistent with previous experiences in the PALACE-1 study and phase II program. Tolerability was improved over the phase II program.

The PALACE-1, 2 & 3 studies are ongoing, and the study extensions remain blinded to investigational sites until all patients complete week 52. Full data from these phase III studies will be submitted for presentation at appropriate medical meetings.

The NDA submission, based on the combined PALACE-1, 2 & 3 studies for PsA, is expected in the first quarter of 2013. A combined MAA submission for PsA and moderate-to-severe psoriasis in Europe is also planned for the second half of 2013.

In a Phase II trial (BCT-001) in patients with Behcet’s disease (BD), a rare inflammatory disorder and area of high unmet medical need, statistical significance was demonstrated for the primary endpoint of the number of oral ulcers at day 85 between apremilast 30 mg BID and placebo. Statistical significance and clinically meaningful responses in other manifestations of BD were also achieved. The overall safety and tolerability profile was consistent with previous experience in other studies with other patient populations. Behcet’s disease is a chronic inflammatory disorder of unknown cause characterized by recurrent oral and genital ulcers; prevalence of BD is highest in the Eastern Mediterranean, the Middle East and East Asia, but is classified as a rare or “orphan” disease by the NIH in the United States and EURODIS in Europe. The Company is currently exploring opportunities to submit for an indication in Behcet’s disease in a number of countries.

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

About PALACE-1, 2 & 3

PALACE-1, 2 & 3 are three pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. 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 extension in which all patients are treated with apremilast. The three PALACE studies included a wide spectrum of patients with active psoriatic arthritis, including those who had been previously treated with DMARD, biologic DMARD, as well as patients who had previously failed a TNF blocker. PALACE-3 includes a large subset of patients with significant skin involvement with psoriasis.

The primary endpoint of the studies is the proportion of patients in each treatment group who achieved the American College of Rheumatology criteria for 20 percent improvement (ACR20) compared to baseline at week 16. Secondary endpoints include other measures of signs and symptoms, physical function and patient-reported outcomes.

Taken together, the PALACE program includes 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 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).

About BCT-001

BCT-001 is a phase 2, multi-center, randomized, placebo-controlled, double-blind, parallel-group study with two treatment arms (apremilast 30mg BID and placebo) in Behcet’s disease. The study consisted of a 90-day pre-randomization phase, a 12-week treatment phase, a 12-week extension phase and a 4-week, observational follow-up phase. A total of 111 subjects with active Behcet’s disease (BD) were randomized 1:1 to receive either apremilast 30mg BID or identically appearing placebo, stratified by gender. The primary endpoint of the study is the number of oral ulcers at day 85 (12 weeks). Because virtually all patients with BD have painful oral ulcers, this manifestation was chosen as the primary efficacy variable. Other less common manifestations of BD, including genital ulcers, skin lesions, inflammatory eye disease, involvement of the gastrointestinal, vascular, and central nervous systems, and pain from oral and genital ulcers were chosen as secondary / exploratory efficacy variables or safety measures.

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 other 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. There are currently no approved oral therapies for this indication in the United States.

About Behcet’s disease

Behcet’s disease (BD) is a chronic inflammatory disorder of unknown cause characterized by recurrent oral and genital ulcers, multiple skin lesions ranging from acne to vasculitic ulcerations, vascular involvement including aneurysms and venous thrombosis, and inflammatory disease of the eye manifesting as uveitis. Prevalence of Behcet’s disease is highest in the Middle East, Asia and Japan, but is classified as a rare or “orphan” disease by the NIH in the United States. At this time, there are no approved oral therapies for this orphan indication in the United States. In some cases, uncontrolled inflammation may lead to blindness, intestinal complications, stroke, and even meningitis, which can be fatal. Although the etiology of BD is unknown, humoral and cellular immune abnormalities have been described.

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. For more information, please visit the Company's website at www.celgene.com.

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Source: Celgene International Sàrl

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