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Oral Apremilast Achieves Statistical Significance for Primary and Secondary Endpoints in a Phase II Trial in Patients with Behçet's Disease
<p class='bwalignc'> <i>Statistically Significant Results in Primary and All Secondary Endpoints Achieved in Rare Orphan Disease</i> </p> <p class='bwalignc'> <i>No Approved Therapies in US or Europe for Rare Chronic Inflammatory Disorder</i> </p> <p class='bwalignc'> </p>
Friday, June 14, 2013
Oral Apremilast Achieves Statistical Significance for Primary and Secondary Endpoints in a Phase II Trial in Patients with Behçet's Disease06:04 EDT Friday, June 14, 2013
BOUDRY, Switzerland (Business Wire) -- Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG) today presented results from a randomized, placebo-controlled phase II trial in patients with Behçet's disease (BD) at EULAR, the European Congress of Rheumatology annual meeting in Madrid.
The Company announced statistical significance for the primary endpoint of the mean number of oral ulcers at week 12 (APR 30 mg BID, 0.5; PBO, 2.1; p<0.0001) evaluating the Company's novel, oral small-molecule inhibitor of phophodiesterase 4 (PDE4) in patients with Behcet's disease. The complete response rate (oral ulcer free) at week 12 was also statistically significant (APR, 71%; PBO, 29%; p<0.0001). Statistically significant and clinically meaningful responses were demonstrated across all secondary endpoints, including all patient-reported outcomes. Notably, improvement in oral ulcer pain (VAS) was significantly higher with apremilast than with placebo (-44.7 vs -16.0; p<0.0001). Among the patients with genital ulcers at baseline (n=16), all 10/10 receiving APR had a complete response at week 12 vs 50% (3/6) receiving PBO (p=0.04).
Behçet's disease is a rare chronic inflammatory disorder of unknown cause characterized by recurrent oral and genital ulcers, skin and eye lesions and commonly joint inflammation as well as involvement of the brain and GI tract. Quality of life during an individual's most productive years is significantly impaired by the disease and life expectancy is significantly shortened for severely affected individuals. Prevalence of Behçet's disease is highest in the Eastern Mediterranean, the Middle East and East Asia; however, it remains classified as a rare or “orphan” disease by the NIH in the United States and EURODIS in Europe. It is estimated that across the high prevalence countries there are approximately 250,000 cases of Behçet's disease.
To date, there are no medicines approved for Behçet's disease in the United States or throughout Europe, and the treatment options depend largely on the manifestations of the different organ systems involved. Current treatment options consist of non-specific symptomatic treatments such as NSAIDS, unapproved immunosuppressive medications and DMARDS.
“I am excited to see the results from this important phase II study,” said VP, Clinical Research and Development, I&I, Randall Stevens. “I think that apremilast could potentially be a very useful addition to our armamentarium for the treatment of Behçet's disease, given the high unmet medical need and the severe impact that mucocutaneous ulcerations can have on a patient's quality of life.”
The overall safety and tolerability profile was consistent with previous experience in other apremilast studies with other patient populations. In BCT-001, treatment-emergent adverse events (TEAE), including severe and serious adverse events and withdrawal due to adverse events were comparable between 30 mg BID and placebo. None of the SAEs on apremilast were reported more than once. Out of the most common TEAEs (top 5) in the 30 mg BID group, two were comparable to placebo, headache and Behçet's syndrome/flare while, nausea, diarrhea and vomiting were reported more frequently with APR 30 mg BID.
These results are from investigational studies. Apremilast is not an approved product for any indication.
The NDA/NDS submissions, based on the combined data from PALACE 1, 2, & 3 for psoriatic arthritis (PsA), were submitted to health authorities in the U.S. and Canada in Q1 2013 and Q2 2013 respectively. The Company previously announced it expects to file a separate NDA/NDS in the U.S./Canada for psoriasis and a combined PsA/psoriasis MAA submission in Europe in the second half of 2013. The Company is currently exploring opportunities to submit for an indication in Behçet's disease in a number of countries.
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 Behçet'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 Behçet'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 Behçet's disease
Behçet'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 Behçet'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 or throughout all of Europe. 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.
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. To learn more go to www.discoverpde4.com/.
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.
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Celgene International Sàrl