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Oral Apremilast Achieves Statistical Significance for the Primary Endpoint of ACR20 in the First Phase III Study (PALACE-1) in

  Oral Apremilast Achieves Statistical Significance for the Primary Endpoint
  of ACR20 in the First Phase III Study (PALACE-1) in Patients with Psoriatic
  Arthritis

Apremilast significantly improves signs and symptoms of PsA in DMARDs-failure
           patients, including biologic-treatment-failure patients

  Apremilast monotherapy demonstrates robust improvement across primary and
                             secondary endpoints

      Highest response demonstrated in biologic-naïve patient population

  No significant safety signals were observed and tolerability improved over
                               phase II program

Business Wire

BOUDRY, Switzerland -- November 13, 2012

Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG)
today presented the results from PALACE-1, the Company’s first Phase III study
in psoriatic arthritis, at the American College of Rheumatology annual meeting
in Washington, D.C.

The company previously announced statistical significance for the primary
endpoint of ACR20 for patients receiving apremilast in the PALACE-1 study, the
first 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 oral disease-modifying antirheumatic drugs (DMARD) and/or biologic
therapy and/or had failed on an anti-tumor necrosis factor (TNF) agent.
Apremilast treatment in this study was used alone or in combination with oral
DMARDs. PALACE-1 is the first phase III study demonstrating statistical
significance in a psoriatic arthritis patient population that included both
prior biologic exposure (23.6%) and biologic failures (9.3%).

In the study, apremilast demonstrated statistically significant and higher
ACR20 responses at week 16 in patients receiving either apremilast 20 or 30 mg
BID monotherapy (31.5% and 50.8% respectively vs. 10.5% for placebo; P<0.05
and P≤0.0001), with no meaningful advantage to adding oral DMARDs to
apremilast. A higher ACR20 response at week 16 was also demonstrated in
biologic-naïve subjects receiving apremilast 30 mg BID monotherapy compared
with placebo (59% vs. 12%; P<0.005).

“The results of this first phase III trial of apremilast are encouraging for
both physicians and patients as a potentially effective and safe oral therapy
for psoriatic arthritis patients,” said Arthur F. Kavanaugh, M.D., Professor
of Clinical Medicine at the University of California, San Diego and Director
of the Center for Innovative Therapy at the University.

Across the entire study population, statistically significant changes in
reducing signs and symptoms of PsA, as measured by the primary endpoint of
ACR20 at week 16, were achieved for patients receiving apremilast 30 mg BID
vs. placebo (41.01% vs. 19.4%; P≤0.0001). This was further supported by a
robust and consistent response (P≤0.0001) across all arthritis-related
secondary endpoints, including ACR50, ACR70, DAS-28, good or moderate EULAR
response achievement and CDAI at week 24. Statistically significant results
were also demonstrated in measures of physical function (HAQ-DI, SF-36
physical function domain score) at week 16 (P=0.0015 and P=0.0049
respectively) and these results were maintained at week 24.

The overall safety profile was consistent with previous experiences in the
phase II program. Importantly, no opportunistic infections (including TB) or
lymphoma were observed through week 24, and there was no increase in risk of
cardiovascular events. Apremilast was generally well tolerated. The majority
of AEs (>95%) were mild or moderate, with serious AEs and discontinuations due
to AEs similar across all treatment arms.

An NDA submission to the U.S. Food and Drug Administration, based on the
combined PALACE program for PsA, is expected in the first half of 2013. The
sNDA submission for psoriasis is expected to follow in the second half of
2013. A combined MAA submission in Europe is also planned for the second half
of 2013.

Top-line positive results from two pivotal randomized, placebo-controlled
phase III studies of apremilast in PsA (PALACE 2 and PALACE 3) were released
in September 2012. Taken together, the PALACE program is comprised of 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 beginning 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).

A randomized, placebo-controlled phase III study (POSTURE) of apremilast in
ankylosing spondylitis (AS) began enrolling patients in April 2012. AS, a
debilitating disease, which may cause fusion of the spine, arthritis,
inflammation of the eye and damage to the heart affects approximately 1.5
million people in the U.S. and Europe. The trial will randomize approximately
450 patients to receive 20mg or 30mg apremilast, or placebo BID. The primary
endpoint is the proportion of patients achieving an ASAS 20 score at week 16.

These results are from an investigational phase III study. Apremilast is not
approved for the treatment of psoriatic arthritis.

About PALACE 1

PALACE-1 is one of three pivotal phase III multi-center, double-blind,
placebo-controlled, parallel-group studies with 2 active-treatment groups.
Approximately 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 primary endpoint of the study is the proportion of patients in each
treatment group who achieved the American College of Rheumatology criteria for
20% improvement (ACR20) compared to baseline at week 16. Secondary endpoints
include other measures of signs and symptoms, physical function and
patient-reported outcomes.

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
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.

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 through gene and protein
regulation. 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.

Contact:

For Celgene International Sàrl
Investors:
+41 32 729 8303
ir@celgene.com
or
Media:
+41 32 729 8304
media@celgene.com
 
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