Oral Apremilast Achieves Statistical Significance for the Primary Endpoint
of PASI-75 in the First Phase III Study (ESTEEM 1) in Patients with
Apremilast significantly improved signs and symptoms of psoriasis across a
range of patient types—from systemic treatment-naïve to biologic-treatment
Apremilast demonstrated significant improvement in the primary endpoint and
major secondary endpoint in the study
No new safety signals were observed; safety and tolerability consistent with
phase III psoriatic arthritis trials
BOUDRY, Switzerland -- March 2, 2013
Celgene International Sàrl, a subsidiary of Celgene Corporation (NASDAQ: CELG)
today presented the results from ESTEEM 1, the Company’s first phase III study
in psoriasis, at the American Academy of Dermatology annual meeting in Miami,
The company previously announced statistical significance for the primary and
major secondary endpoint of PASI-75 at Week 16 and the Static Physician Global
Assessment for patients receiving apremilast in the ESTEEM 1&2 phase III
studies. ESTEEM 1&2 are the phase III registrational randomized,
placebo-controlled studies evaluating the Company’s oral small-molecule
inhibitor of phosphodiesterase-4 (PDE4) in patients with moderate-to-severe
chronic plaque psoriasis.
ESTEEM 1, presented today, evaluated efficacy and safety in a range of
patients. Approximately one-third of the study population was systemic and/or
phototherapy treatment-naïve. Nearly 30 percent of the overall study
population had prior biologic therapy, which included biologic-failures.
In the ESTEEM 1 study, a significantly higher percentage of apremilast-treated
patients demonstrated PASI-75 at week 16 than did placebo patients (33.1% vs.
5.3%; P<0.0001). Significantly higher PASI-75 scores at week 16 were
demonstrated across all patient segments enrolled in this study, including
systemic-naïve and biologic-naïve patients receiving apremilast 30 mg BID
compared with placebo (38.7% vs. 7.6%; P<0.0001 and 35.8% vs. 5.9%; P<0.0001
respectively). Apremilast demonstrated maintenance of effect over time, as
measured by the Mean Percent Change from Baseline in PASI score over 32 weeks,
with apremilast demonstrating a 54.9% reduction at week 16 and a 61.9%
reduction at week 32.
Statistical significance at week 16 was also demonstrated in the major
secondary endpoint, Static Physician Global Assessment (sPGA) of clear or
almost clear (P<0.0001), and other key secondary endpoints (change in BSA,
Pruritus VAS, DLQI), as well as in assessments of difficult to treat areas
(nail and scalp psoriasis).
“I see this as a prime candidate for future management of psoriasis that
allows us to treat a range of patients, including more moderate cases earlier
on,” said Kristian Reich, M.D., SCIderm Research Institute and Dermatologikum
The overall safety and tolerability profile was consistent with results from
previously reported phase III psoriatic arthritis trials. No cases of
tuberculosis or lymphoma were observed through week 16, and there was no
increased risk of cardiovascular events or serious opportunistic infection.
Apremilast was generally well tolerated. The most common adverse events (AEs)
greater than placebo were diarrhea, nausea and headache. Greater than 96% of
patients in the study reported no AEs or mild to moderate AEs. A similar
percentage of patients reported both serious AEs and severe AEs in the
apremilast 30 mg BID treatment group compared to placebo (2.1% vs. 2.8% and
3.6% vs. 3.2%, respectively).
An NDA submission to the U.S. Food and Drug Administration, based on the
combined ESTEEM 1&2 studies for psoriasis, is expected in the second half of
2013. The Company previously announced it expects to file a separate NDA for
psoriatic arthritis in the first quarter of 2013. A combined PsA/psoriasis MAA
submission in Europe is also planned for the second half of 2013.
Top-line positive results from the two pivotal, randomized, placebo-controlled
phase III studies of apremilast in psoriasis (ESTEEM 1&2) were released in
January 2013. The studies included more than 1,200 patients with
moderate-to-severe psoriasis and are ongoing. Results from PSOR-005, a phase
IIb dose-range study, were recently published in The Lancet
About ESTEEM 1 & 2
ESTEEM 1 & 2 are two pivotal phase III randomized, placebo-controlled studies
evaluating apremilast in subjects with a diagnosis of moderate-to-severe
chronic plaque psoriasis for at least 12 months prior to the screening, and at
baseline, and who were also candidates for phototherapy and/or systemic
therapy. Approximately 1,250 patients were randomized 2:1 to receive either
apremilast 30 mg BID or placebo for the first 16 weeks, followed by a
maintenance phase from weeks 16-32 in which placebo subjects were switched to
apremilast 30 mg BID through week 32, and a randomized withdrawal phase for
responders from Week 32-Week 52 based on their initial apremilast
randomization and PASI response.
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 (see
http://discoverpde4.com/). 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. To learn more
go to www.discoverpde4.com/.
Top-line positive results from three pivotal randomized, placebo-controlled
phase III studies of apremilast in PsA (PALACE 1, 2 & 3) were released in
September 2012. PALACE 1 was also presented as an oral presentation at the ACR
annual meeting in November 2012. Taken together, the PALACE program comprises
the most comprehensive psoriatic arthritis studies to date intended for
Results from PSA-001, the phase II study of apremilast in psoriatic arthritis,
were recently published online in the journal Arthritis & Rheumatism
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 20 mg or 30 mg apremilast BID, or placebo BID.
Psoriasis is an immune-mediated, non-contagious chronic inflammatory skin
disorder of unknown cause. The disorder is a chronic recurring condition that
varies in severity from minor localized patches to complete body coverage.
Plaque psoriasis is the most common type of psoriasis. About 80 percent of
people who develop psoriasis have plaque psoriasis, which appears as patches
of raised, reddish skin covered by silvery-white scales. These patches, or
plaques, frequently form on the elbows, knees, lower back, and scalp.
Psoriasis occurs nearly equally in males and females. Recent studies show that
there may be an ethnic link. Psoriasis is believed to be most common in
Caucasians and slightly less common in other ethnic groups. Worldwide,
psoriasis is most common in Scandinavia and other parts of northern Europe.
About 10 percent to 30 percent of patients with psoriasis also develop a
condition called psoriatic arthritis, which causes pain, stiffness and
swelling in and around the joints.
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
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