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Oral Apremilast Demonstrated Rapid, Clinically Significant Improvements in Oral Ulcers in Patients with Behçet’s Disease in a Phase II Trial
|BOUDRY, Switzerland - Monday, October 28th 2013 [ME NewsWire]|
71% of patients achieved complete response at week 12 in clearing of ulcers
Apremilast also improved quality of life measures and pain associated with active oral ulcers, the cardinal manifestation of Behçet’s disease
Limited therapies currently available in U.S. or Europe for this orphan chronic inflammatory disorder
(BUSINESS WIRE)-- Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation (NASDAQ:CELG), today presented phase II trial (BCT-001) results of apremilast, the Company’s first-in-class, oral, targeted inhibitor of phosphodiesterase 4 (PDE4), in patients with Behçet’s disease. The findings were presented at the 2013 American College of Rheumatology (ACR)/Association of Rheumatology Health Professionals (ARHP) annual meeting in San Diego. These results have been featured as part of the official ACR press program, which highlights data considered representative of the highest quality and most meaningful research presented at the ACR annual meeting.
Behçet’s disease is a rare and chronic inflammatory disorder characterized by recurrent oral and genital ulcers, skin and eye lesions (which may cause blindness) and joint inflammation. Inflammation may also affect the brain and gastrointestinal tract.
These data, which were also presented at the European League Against Rheumatism (EULAR) annual meeting this year in June, showed that significantly more patients on apremilast achieved a complete response (were free from active oral ulcers) at week 12 compared with those on placebo (apremilast, 71%; placebo, 29%; p<0.0001). Among patients with genital ulcers at baseline (n=16), 100% of those receiving apremilast had a complete response at week 12 compared with 50% of those receiving placebo (p=0.036).
"Behçet’s disease can have a severe negative impact on patients’ quality of life, and there are limited therapies available, so there is a clear need for a new therapy to help this patient population,” said Gulen Hatemi, M.D., Associate Professor, Cerrahpasa Medical School, Istanbul, Turkey. "We are encouraged by the rapid response seen in this important phase II study and by apremilast’s potential to treat oral ulcers in this orphan disease.”
The beneficial effect of apremilast on oral ulcers reached a stable effect within two weeks and was sustained while patients remained on treatment.
At week 12, apremilast also improved several patient-reported outcome scores, including the Behçet’s disease current activity form (BDCAF), Behçet’s syndrome activity score (BSAS) and Behçet’s disease quality of life (QoL) instrument. Improvement in oral ulcer pain was also significantly higher with apremilast than with placebo (apremilast, -44.7 ± 24.30; placebo, -16.0 ± 32.54; p<0.0001).
The type and severity of adverse events (AEs) were comparable to the known apremilast safety profile. In BCT-001, treatment-emergent adverse events (TEAE), including severe and serious adverse events (SAEs) and withdrawal due to adverse events, were comparable between 30 mg twice daily (BID) and placebo. None of the SAEs in the apremilast group were reported more than once. Out of the five most common TEAEs in the 30 mg BID group, two (headache and Behçet’s syndrome/flare) were comparable to placebo, while nausea, diarrhea and vomiting were reported more frequently with APR 30 mg BID.
Limited therapies are available to treat this rare, chronic inflammatory disorder of unknown cause. The treatment options depend largely on the manifestations of the different organ systems involved. Treatment options recommended by physicians are largely aimed at alleviating specific patient symptoms and may include non-steroidal anti-inflammatory drug (NSAIDS), immunosuppressive medications and disease-modifying antirheumatic drugs (DMARDS) approved for other indications.
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 & 3 for psoriatic arthritis, were submitted to health authorities in the US 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, is on-track for the fourth quarter 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 30 mg 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 four-week post-treatment observational follow-up phase. A total of 111 subjects with active Behçet’s disease were randomized 1:1 to receive either apremilast 30 mg BID or identically appearing placebo, stratified by gender. The primary endpoint of the study was the number of oral ulcers at day 85 (12 weeks). Because virtually all patients with Behçet’s disease have painful oral ulcers, this manifestation was chosen as the primary efficacy measure. Less common manifestations of Behçet’s disease, 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.
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 Behçet’s Disease
Behçet’s disease is a chronic inflammatory vasculitis of unknown cause characterized by recurrent oral and genital ulcers, multiple skin lesions ranging from acne to vasculitic ulcerations, vascular involvement, including venous thrombosis and aneurysms which may be life threatening, and inflammatory disease of the eye manifesting as uveitis (may lead to blindness), neurologic involvement and gastrointestinal involvement. Prevalence of Behçet’s disease is highest in the Middle East, Asia and Japan, but it is classified as a rare or "orphan” disease by the NIH in the United States. At this time, there are limited therapies for this orphan indication in the United States or throughout Europe. In some cases, uncontrolled inflammation may lead to blindness, intestinal perforations, stroke, and even aneurismal bleeding which can be fatal. Although the root cause of Behçet’s disease is unknown, the disease is associated with abnormalities of the immune system. To learn more about the role of PDE4 in inflammatory diseases, visit www.discoverpde4.com.
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.
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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