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.
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 our Annual Report
on Form 10-K and our other reports filed with the Securities and
Exchange Commission.
