Oral Apremilast Monotherapy Demonstrated Long-Term Clinical Benefits in
Psoriatic Arthritis Patients Naïve to Previous DMARD Therapy
PALACE 4 achieves primary endpoint of ACR 20 at week 16 with nearly 60 percent
of patients who completed 52 weeks on apremilast achieving an ACR 20 response
PALACE 4 is the first large randomized controlled study to examine the
efficacy and safety of a novel agent in patients naïve to previous DMARD
Long-term, clinically meaningful improvements seen in manifestations of
psoriatic arthritis such as physical function (HAQ-DI), skin (PASI-75/50),
swollen and tender joints, enthesitis and dactylitis
BOUDRY, Switzerland -- October 29, 2013
Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation
(NASDAQ:CELG), today announced results of its long-term phase III study on
apremilast, the Company’s first-in-class oral, targeted inhibitor of
phosphodiesterase 4 (PDE4), in systemic or biologic DMARD-naïve psoriatic
arthritis patients at the 2013 American College of Rheumatology
(ACR)/Association of Rheumatology Health Professionals (ARHP) annual meeting
in San Diego.
PALACE 4 is the first large, randomized, controlled study to examine the
efficacy and safety of a novel agent exclusively in systemic or biologic
DMARD-naïve psoriatic arthritis patients. Apremilast monotherapy demonstrated
clinical benefits over 52 weeks in this treatment-naïve patient population,
including clinically meaningful improvements in signs and symptoms of
psoriatic arthritis, as well as manifestations of psoriatic arthritis such as
physical function (HAQ-DI), skin (PASI-75/50), swollen and tender joints,
enthesitis and dactylitis.
At week 16, a statistically significantly greater proportion of patients
treated with apremilast monotherapy achieved a modified ACR20 (the study’s
primary endpoint) versus placebo: 29.2% (apremilast 20 mg; P=0.0076) and 32.3%
(apremilast 30 mg; P=0.0011) versus 16.9% (placebo). For those patients
randomized to apremilast and completing 52 weeks of the study, an ACR20
response of 53.4% (apremilast 20 mg) and 58.7% (apremilast 30 mg) at week 52
was observed. ACR 50 and 70 was reached by 31.9% and 18.1% of patients,
respectively, for apremilast 30 mg.
“In addition to maintaining its long-term safety and tolerability profile
consistent with the previously reported data, apremilast monotherapy showed
significant clinical benefit in systemic or biologic DMARD-naïve psoriatic
arthritis patients,” said Alvin Wells, M.D., Ph.D., Director, Rheumatology and
Immunotherapy Center, Franklin, WI, US. “These encouraging results suggest
that apremilast may have the potential to be used alone and as a first-line
Durable improvements in multiple endpoints—including enthesitis (inflammation
at sites where tendons, ligaments or joint capsule fibers insert into bone),
dactylitis (swelling of a finger or toe), impaired physical function as
assessed by HAQ-DI, swollen and tender joint counts and associated skin
psoriasis—were maintained or increased in patients completing 52 weeks of
Apremilast monotherapy demonstrated an acceptable safety profile and was
generally well-tolerated up to 52 weeks. No new safety concerns were
identified with longer treatment duration, and the profile was consistent with
previously reported safety data on apremilast. The most common adverse events
(AEs) reported through 52 weeks were nausea, diarrhea and headache.
Discontinuation rates for diarrhea and nausea in the combined apremilast
treatment groups were less than 2% over 52 weeks. No serious AEs of diarrhea
or nausea were reported in any treatment group up to 52 weeks. No systemic
opportunistic infections, including no cases of tuberculosis (new or
reactivations), were reported.
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 and 3 for psoriatic arthritis, were submitted
to health authorities in the U.S. 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, are on-track for the fourth quarter
About PALACE Program
PALACE 1, 2, 3 and 4 are the pivotal phase III multi-center, double-blind,
placebo-controlled, parallel-group studies with two active-treatment groups.
In PALACE 1, 2 and 3, 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 active treatment phase up to 52 weeks
followed by a long-term safety phase in which all patients are treated with
apremilast. The PALACE 1, 2 and 3 studies included a wide spectrum of patients
with active psoriatic arthritis, including those who had been previously
treated with oral DMARDs, and/or biologic DMARDs, including patients who had
previously failed a tumor necrosis factor (TNF) blocker. PALACE 3 includes a
large subset of patients with significant skin involvement with psoriasis.
In PALACE 4, more than 500 DMARD-naïve patients 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 active treatment phase up to 52
weeks, followed by a long-term safety phase in which all patients are treated
The primary endpoint of the PALACE 1, 2, 3 and 4 studies is the modified
American College of Rheumatology criteria for 20 percent improvement (ACR20)
at week 16. Secondary endpoints include other measures of signs and symptoms,
physical function and patient-reported outcomes at weeks 16 and 24.
Taken together, the PALACE program includes the most comprehensive psoriatic
arthritis program to date intended for regulatory submission.
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 Psoriatic Arthritis
Psoriatic arthritis is a painful, chronic inflammatory disease associated with
the skin condition psoriasis. An estimated 125 million people worldwide have
psoriasis, approximately 30 percent of whom may also develop psoriatic
arthritis. Psoriatic arthritis is a chronic disorder with progressive and
additive joint inflammation that can lead to deleterious effects on quality of
life and increases work disability. In addition to psoriatic skin lesions,
common signs and symptoms of psoriatic arthritis include pain, stiffness and
swelling in several to many joints, as well as inflammation of the spine.
Patients often experience psoriasis on average for 10 years before the onset
of joint symptoms, and many psoriatic arthritis patients go undiagnosed. To
learn more about psoriatic arthritis, go to www.discoverpsa.com. To learn more
about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.
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.
This press release contains forward-looking statements, which are generally
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Celgene International Sàrl
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