Oral Apremilast Demonstrated Rapid, Clinically Significant Improvements in
Oral Ulcers in Patients with Behçet’s Disease in a Phase II Trial
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
BOUDRY, Switzerland -- October 28, 2013
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
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 ±
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
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.
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