Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ:
CELG) today announced that statistical significance was achieved for the
primary endpoint of ACR 20 at week 16 for patients receiving apremilast
20 mg and 30 mg BID monotherapy in PALACE 4. PALACE 4 is the fourth
randomized, placebo-controlled study evaluating the Company's novel,
oral small-molecule inhibitor of phosphodiesterase 4 (PDE4) in patients
with psoriatic arthritis. This is the first Company-sponsored trial
studying patients who had not previously received an oral
disease-modifying antirheumatic drug (DMARD).
"Despite recent advances in the treatment of psoriatic arthritis, there
remains a significant need for more oral DMARD treatment options for
DMARD-naïve patients," said Randall Stevens, VP of Clinical Research and
Development for Inflammation & Immunology. "PALACE-4 is now the fourth
major randomized apremilast Phase III study to provide promising results
for patients with psoriatic arthritis."
Patients on apremilast also achieved a statistically significant benefit
over placebo in key secondary endpoints, as demonstrated in various
measures of physical function and signs and symptoms, including
No new safety and tolerability signals identified, with fewer AEs and
SAEs reported than in PALACE 1, 2&3. Importantly, in PALACE 4, no
systemic opportunistic infections (including TB) or lymphoma were
observed through week 24, and there was no increase in risk of
cardiovascular events. The most common AEs in PALACE 4 (?5%) were
nausea, diarrhea and headache.
The PALACE 4 study is ongoing and the study extension remains blinded
until all patients complete week 52. Full data from this phase III study
will be submitted for presentation at appropriate medical meetings.
Results from PALACE 1, one of three registrational randomized,
placebo-controlled phase III studies of apremilast in PsA were released
at ACR in November 2012. Top-line positive results from the two
additional registrational studies of apremilast in PsA (PALACE 2 and
PALACE 3) were released in September 2012. Twenty-four-week topline
results of PALACE 3 and 52-week results from PALACE 1 will be presented
at EULAR in June 2013. Taken together, the PALACE program is the most
comprehensive set of psoriatic arthritis studies to date intended for
regulatory submission. Results from the PSA-001 phase II study of
apremilast in psoriatic arthritis were recently published online in the
journal Arthritis & Rheumatism (http://www.onlinelibrary.wiley.com/doi/10.1002/art.34627/abstract).
In addition, positive results from two large, pivotal global studies of
apremilast in more than 1,200 patients with moderate-to-severe plaque
psoriasis (ESTEEM 1 and 2) were released in January 2013, with full
results from ESTEEM 1 presented at AAD in March. Results from PSOR-005,
a phase IIb dose-range study of apremilast in psoriasis, were recently
published in The Lancet (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 and affects
approximately 2.5 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.
The NDA/NDS submissions, based on the combined data from PALACE 1, 2 &3
for PsA, were submitted to health authorities in the US and Canada in
Q12013 and Q2 2013 respectively. The Company previously announced it
expects to file a separate NDA in the US for psoriasis and a combined
PsA/psoriasis MAA submission in Europe in the second half of 2013.
About PALACE 4
PALACE 4 is one of four pivotal phase III multi-center,
double-blind, placebo-controlled, parallel-group studies with 2
active-treatment groups in a DMARD-naïve patient population. More than
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.
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-?, 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/.
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.
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.
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
Celgene International Sàrl
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