Oral Apremilast Demonstrated Long-Term Clinical Benefits for Patients with
Up to 63 percent of patients achieved ACR 20 at week 52, generally consistent
with PALACE 1
Clinically meaningful improvements demonstrated in all key manifestations of
psoriatic arthritis at week 52
Apremilast demonstrated a consistent safety profile across three long-term
PALACE phase III studies of 1493 patients over 52 weeks
Tolerability improved in pooled analysis between weeks 24 and 52
No clinically meaningful changes in laboratory measurements were demonstrated
in the pooled analyses
BOUDRY, Switzerland -- October 28, 2013
Celgene International Sàrl, a wholly-owned subsidiary of Celgene Corporation
(NASDAQ: CELG), today announced results of three long-term (52-week) phase III
studies of apremilast, the Company’s first-in-class, oral, targeted inhibitor
of phosphodiesterase 4 (PDE4), in psoriatic arthritis at the 2013 American
College of Rheumatology (ACR)/Association of Rheumatology Health Professionals
(ARHP) annual meeting in San Diego. The studies included 52-week efficacy
results from PALACE 2 and 3 and 52-week pooled safety data analyses from
PALACE 1, 2 and 3, including effects on laboratory measurements.
“Psoriatic arthritis is a debilitating chronic disease requiring long-term
treatment,” stated Maurizio Cutolo, M.D., Research Laboratories and Clinical
Academic Division of Rheumatology at the University Medical School of Genova,
Italy. “The one-year data from the PALACE trials suggest that, with continued
treatment, early responses to apremilast are durable over time. Based on the
efficacy and safety data to date from phase III studies, apremilast has the
potential to offer an additional treatment option for the long-term management
of psoriatic arthritis.”
PALACE 2 and PALACE 3: 52-week efficacy data
Three pivotal studies (PALACE 1, 2 and 3) were conducted in patients with
active psoriatic arthritis who had prior experience with conventional DMARDs
and/or biologics. The long-term (52 weeks) results from PALACE 1 have been
previously reported. Today, the long-term results from the two additional
pivotal phase III studies (PALACE 2 and PALACE 3) were reported. Consistent
with the results from PALACE 1, significantly more patients receiving
apremilast 20 mg or 30 mg twice daily (BID) achieved a modified American
College of Rheumatology (ACR) 20 response at week 16 (primary endpoint) than
did patients taking placebo in both PALACE 2 (placebo, 20%; apremilast 20 mg
BID, 38%, P=0.0002; apremilast 30 mg BID, 34%, P=0.0024) and PALACE 3
(placebo, 19%; apremilast 20 mg BID, 29%, P<0.05; apremilast 30 mg BID, 43%,
P<0.0001). Clinically meaningful improvements were also demonstrated in signs
and symptoms, physical function and other manifestations chartacteristic of
psoriatic arthritis, including swollen and tender joints, skin and quality of
Sustained improvements in the percentage of patients achieving a modified ACR
20 response at week 52 were observed in both PALACE 2 (apremilast 20 mg BID,
52.9%; apremilast 30 mg BID, 52.6%) and PALACE 3 (apremilast 20 mg BID, 56.0%;
apremilast 30 mg BID, 63.0%) for those patients randomized to apremilast and
completing 52 weeks of treatment.
PALACE 1, PALACE 2 and PALACE 3: pooled 52-week safety data
Long-term (52 weeks) safety results from a pooled analysis of the PALACE 1, 2
and 3 trials (including 1,493 patients) identified no new safety findings for
patients with psoriatic arthritis who were treated with apremilast for up to
52 weeks, compared with the previously reported 24 week safety results.
Previously reported adverse events (AEs) were less frequent in weeks 24 to 52
than in weeks 0 to 24.
Most AEs were mild or moderate in severity and did not lead to
discontinuation. The most commonly reported AEs were nausea, diarrhea,
headache, upper respiratory tract infection and nasopharyngitis. Nausea and
diarrhea were predominantly mild in severity, occurred most frequently in the
first two weeks of treatment, and often resolved within a month despite
continued treatment. Serious AEs occurred at low rates, were comparable across
treatment groups and did not increase with long-term apremilast exposure,
based on exposure-adjusted incidence rates per 100 subject years.
Exposure-adjusted incidence rates per 100 subject years of major adverse
cardiac events, serious infections, including opportunistic infections, and
malignancies were comparable with those of placebo. No cases of tuberculosis
(new or reactivations) were reported with either dose of apremilast.
PALACE 1, PALACE 2 and PALACE 3: laboratory monitoring
The effect of apremilast on laboratory measurements was also assessed in a
pooled analysis of 1,493 patients (placebo, 495; apremilast 20 mg BID, 501;
apremilast 30 mg BID, 497) with psoriatic arthritis from the PALACE 1, 2 and 3
trials. No clinically meaningful changes in laboratory measurements were
noted, suggesting that ongoing laboratory monitoring may not be necessary.
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
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 Celgene Corporation’s Annual
Report on Form 10-K and other reports filed with the Securities and Exchange
+41 32 729 8303 firstname.lastname@example.org
+41 32 729 8304 email@example.com
Press spacebar to pause and continue. Press esc to stop.