Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ: CELG), today announced results of three long-term (52-week) phase III studies of apremilast, the Company’s first-in-class, oral, targeted inhibitor of phosphodiesterase 4 (PDE4), in psoriatic arthritis at the 2013 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) annual meeting in San Diego. The studies included 52-week efficacy results from PALACE 2 and 3 and 52-week pooled safety data analyses from PALACE 1, 2 and 3, including effects on laboratory measurements. “Psoriatic arthritis is a debilitating chronic disease requiring long-term treatment,” stated Maurizio Cutolo, M.D., Research Laboratories and Clinical Academic Division of Rheumatology at the University Medical School of Genova, Italy. “The one-year data from the PALACE trials suggest that, with continued treatment, early responses to apremilast are durable over time. Based on the efficacy and safety data to date from phase III studies, apremilast has the potential to offer an additional treatment option for the long-term management of psoriatic arthritis.” PALACE 2 and PALACE 3: 52-week efficacy data Three pivotal studies (PALACE 1, 2 and 3) were conducted in patients with active psoriatic arthritis who had prior experience with conventional DMARDs and/or biologics. The long-term (52 weeks) results from PALACE 1 have been previously reported. Today, the long-term results from the two additional pivotal phase III studies (PALACE 2 and PALACE 3) were reported. Consistent with the results from PALACE 1, significantly more patients receiving apremilast 20 mg or 30 mg twice daily (BID) achieved a modified American College of Rheumatology (ACR) 20 response at week 16 (primary endpoint) than did patients taking placebo in both PALACE 2 (placebo, 20%; apremilast 20 mg BID, 38%, P=0.0002; apremilast 30 mg BID, 34%, P=0.0024) and PALACE 3 (placebo, 19%; apremilast 20 mg BID, 29%, P<0.05; apremilast 30 mg BID, 43%, P<0.0001). Clinically meaningful improvements were also demonstrated in signs and symptoms, physical function and other manifestations chartacteristic of psoriatic arthritis, including swollen and tender joints, skin and quality of life. Sustained improvements in the percentage of patients achieving a modified ACR 20 response at week 52 were observed in both PALACE 2 (apremilast 20 mg BID, 52.9%; apremilast 30 mg BID, 52.6%) and PALACE 3 (apremilast 20 mg BID, 56.0%; apremilast 30 mg BID, 63.0%) for those patients randomized to apremilast and completing 52 weeks of treatment.
PALACE 1, PALACE 2 and PALACE 3: pooled 52-week safety dataLong-term (52 weeks) safety results from a pooled analysis of the PALACE 1, 2 and 3 trials (including 1,493 patients) identified no new safety findings for patients with psoriatic arthritis who were treated with apremilast for up to 52 weeks, compared with the previously reported 24 week safety results. Previously reported adverse events (AEs) were less frequent in weeks 24 to 52 than in weeks 0 to 24. Most AEs were mild or moderate in severity and did not lead to discontinuation. The most commonly reported AEs were nausea, diarrhea, headache, upper respiratory tract infection and nasopharyngitis. Nausea and diarrhea were predominantly mild in severity, occurred most frequently in the first two weeks of treatment, and often resolved within a month despite continued treatment. Serious AEs occurred at low rates, were comparable across treatment groups and did not increase with long-term apremilast exposure, based on exposure-adjusted incidence rates per 100 subject years. Exposure-adjusted incidence rates per 100 subject years of major adverse cardiac events, serious infections, including opportunistic infections, and malignancies were comparable with those of placebo. No cases of tuberculosis (new or reactivations) were reported with either dose of apremilast. PALACE 1, PALACE 2 and PALACE 3: laboratory monitoring The effect of apremilast on laboratory measurements was also assessed in a pooled analysis of 1,493 patients (placebo, 495; apremilast 20 mg BID, 501; apremilast 30 mg BID, 497) with psoriatic arthritis from the PALACE 1, 2 and 3 trials. No clinically meaningful changes in laboratory measurements were noted, suggesting that ongoing laboratory monitoring may not be necessary. 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 ProgramPALACE 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.