|[March 23, 2014]
Oral OTEZLA® (apremilast) Demonstrated Clinically Meaningful and Sustained Improvements in Skin, Nail and Scalp of Adult Patients with Moderate to Severe Plaque Psoriasis
SUMMIT, N.J. --(Business Wire)--
Celgene Corporation (NASDAQ:CELG) today released new research findings
on OTEZLA® (apremilast), the Company's oral, selective
inhibitor of phosphodiesterase 4 (PDE4), from the ESTEEM 1 and 2 phase
III studies in patients with moderate to severe plaque psoriasis at the
72nd Annual Meeting of the American Academy of Dermatology
(AAD) Annual Meeting in Denver, CO.
In ESTEEM 1 and 2 patients received OTEZLA 30 mg twice daily (BID) or
placebo for the first 16 weeks, followed by a maintenance phase through
week 32 in which patients on placebo for 16 weeks were switched to
OTEZLA. Patients initially randomized to OTEZLA 30 mg BID and who were
PASI 75 (psoriasis area and severity index) responders at week 32 were
re-randomized to either OTEZLA 30 mg BID or placebo.
ESTEEM 1 demonstrated a stable mean PASI improvement of 81 to 88 percent
between weeks 32 and 52 for those patients who were treated for 52 weeks
with OTEZLA 30 mg BID and who achieved a PASI-75 score at week 32
(n=77). These data are consistent with the mean PASI-75 improvement
observed between weeks 16 and 32.
In the same group of patients, OTEZLA 30 mg BID continued to demonstrate
improvements in difficult-to-treat areas affected by plaque psoriasis.
Among patients who had nail psoriasis at baseline (n=46), the majority
showed meaningful improvement in their nails. A mean percent decrease
from baseline in the Nail Psoriasis Severity Index (NAPSI) of 60.2
percent was observed at week 52. Of those patients who had scalp
psoriasis defined as moderate or greater at baseline (n=49), the
majority continued to demonstrate meaningful improvement in their scalp
psoriasis with 72.9 percent having reduction of their scalp symptoms to
clear or almost clear (ScPGA 0 or 1) at week 52.
In ESTEEM 2, a significantly higher percentage of patients receiving
OTEZLA 30 mg BID achieved a PASI-75 response at week 16 (primary
endpoint) compared with patients who received placebo (28.8 percent vs.
5.8 percent; p<0.0001). Statistical significance at week 16 was also
demonstrated for the major secondary endpoint, static Physician Global
Assessment (sPGA) score of clear or almost clear (p<0.0001).
The beneficial effects of OTEZLA on psoriasis in
difficult-to-treat areas of scalp, nails, palms and soles were also
demonstrated in ESTEEM 2. After 16 weeks of treatment, OTEZLA 30
mg BID demonstrated significantly higher response rates versus placebo
for psoriasis affecting the scalp (ScPGA 0-1: 40.9 percent vs. 17.2
percent; p<0.0001), nails (NAPSI-50: 44.6 percent vs. 18.7 percent;
p<0.0001), and palm and soles (Palmoplantar Physician Global Assessment
(PPPGA) 0-1: 65.4 percent vs. 31.3 percent; nominal p=0.0315).
"Psoriasis of the nails, scalp and palmoplantar regions is very
difficult to treat and can be debilitating for individuals dealing with
this chronic disease," said Jennifer Cather, MD, Modern Research
Associates, Dallas, Texas. "Results from the 52-week analysis of the
ESTEEM program suggest that early responses seen with OTEZLA treatment
in multiple efficacy endpoints of plaque psoriasis, including difficult
to treat areas, are durable over time. Together with the observed
long-term consistent safety and tolerability profile, these findings are
A separate analysis of long-term (52-week) safety and tolerability data
from ESTEEM 1 identified no new or unexpected adverse events (AEs) for
patients treated with OTEZLA compared with results at week 16. The most
frequently reported AEs during the placebo-controlled period and the
long-term 52-week OTEZLA-exposure period were diarrhea,
upper-respiratory tract infection, nausea, nasopharyngitis, tension
headache, and headache. Discontinuation rates for diarrhea and nausea
were each less than 2 percent in the OTEZLA 30 mg BID group through week
52. No serious AEs of diarrhea and nausea were reported in all groups
through 52 weeks. Serious AEs were similar between placebo and OTEZLA in
the first 16 weeks, and the rate did not change through the 52-week
OTEZLA-exposure period. No clinically meaningful changes in laboratory
measurements were identified over the OTEZLA 52-week exposure period.
No new or unexpected AEs were identified for patients treated with
OTEZLA in ESTEEM 2.
In a pooled analysis of ESTEEM 1 and 2, exposue-adjusted incidence
rates (per 100 patient-years) for major adverse cardiac events, serious
infections including systemic opportunistic infection, or malignancies
were comparable between placebo and OTEZLA treatment groups.
OTEZLA is not indicated for the treatment of patients with psoriasis in
OTEZLA was approved on March 21, 2014 by the U.S. Food and Drug
Administration (FDA) for the treatment of adults with active psoriatic
arthritis. A New Drug Submission (NDS (News - Alert)) based on the combined data from
the PALACE 1, 2 and 3 trials for psoriatic arthritis was submitted to
health authorities in Canada in the second quarter of 2013. A New Drug
Application (NDA) for psoriasis in the U.S., a NDS for psoriasis in
Canada as well as a combined psoriatic arthritis/psoriasis Marketing
Authorization Application (MAA) in Europe were all submitted to health
authorities in the fourth quarter of 2013.
About ESTEEM 1 and 2
ESTEEM 1 and 2 are two large pivotal phase III randomized,
placebo-controlled studies evaluating OTEZLA in patients with a
diagnosis of moderate to severe plaque psoriasis for at least 12 months
prior to screening, and who were also candidates for phototherapy and/or
systemic therapy. Approximately 1,250 patients were randomized 2:1 to
receive either OTEZLA 30 mg twice daily or placebo after an initial
five-day titration period, for the first 16 weeks, followed by a
maintenance phase from weeks 16-32 in which placebo patients were
switched to OTEZLA 30 mg twice daily through week 32, and a randomized
withdrawal phase for responders from week 32 to week 52 based on their
initial OTEZLA randomization and PASI-75 response.
OTEZLA is an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4)
specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition
results in increased intracellular cAMP levels.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR ADULTS WITH PSORIATIC
OTEZLA® (apremilast) is indicated for the treatment of adult patients
with active psoriatic arthritis.
IMPORTANT SAFETY INFORMATION
OTEZLA is contraindicated in patients with a known hypersensitivity to
apremilast or to any of the excipients in the formulation.
Warnings and Precautions
Depression: Treatment with OTEZLA is associated with an increase in
adverse reactions of depression. During clinical trials, 1.0% (10/998)
of patients treated with OTEZLA reported depression or depressed mood
compared to 0.8% (4/495) treated with placebo; 0.3% (4/1441) of patients
treated with OTEZLA discontinued treatment due to depression or
depressed mood compared with none in placebo treated patients (0/495).
Depression was reported as serious in 0.2% (3/1441) of patients exposed
to OTEZLA, compared to none in placebo treated patients (0/495).
Suicidal ideation and behavior were observed in 0.2% (3/1441) of
patients on OTEZLA, compared to none on placebo (0/495). Two patients
who received placebo committed suicide compared to none on OTEZLA.
Carefully weigh the risks and benefits of treatment with OTEZLA for
patients with a history of depression and/or suicidal thoughts/behavior,
or in patients who develop such symptoms while on OTEZLA. Patients,
caregivers, and families should be advised of the need to be alert for
the emergence or worsening of depression, suicidal thoughts or other
mood changes, and they should contact their healthcare provider if such
Weight Decrease: Body weight loss of 5-10% was reported in 10% of
patients taking OTEZLA and in 3.3% of patients taking placebo. Monitor
body weight regularly; evaluate unexplained or clinically significant
weight loss, and consider discontinuation of OTEZLA.
Drug Interactions: Apremilast exposure was decreased when OTEZLA was
co-administered with rifampin, a strong CYP450 enzyme inducer; loss of
OTEZLA efficacy may occur. Concomitant use of OTEZLA with CYP450 enzyme
inducers (eg, rifampin, phenobarbital, carbamazepine, phenytoin) is not
Adverse reactions reported in at least 2% of patients taking OTEZLA,
that occurred at a frequency at least 1% higher than that observed in
patients taking placebo, for up to 16 weeks (after the initial 5-day
titration), were (OTEZLA%, placebo%): diarrhea (7.7, 1.6); nausea (8.9,
3.1); headache (5.9, 2.2); upper respiratory tract infection (3.9, 1.8);
vomiting (3.2, 0.4); nasopharyngitis (2.6, 1.6); upper abdominal pain
Use in Specific Populations
Pregnancy and Nursing Mothers: OTEZLA is Pregnancy Category C; it has
not been studied in pregnant women. Use during pregnancy only if the
potential benefit justifies the potential risk to the fetus. It is not
known whether apremilast or its metabolites are present in human milk.
Caution should be exercised when OTEZLA is administered to a nursing
Renal Impairment: OTEZLA dosage should be reduced in patients with
severe renal impairment (creatinine clearance less than 30 mL/min); for
details, see Dosage and Administration, Section 2, in the Full
here for Full Prescribing Information.
Psoriasis is an immune-mediated, non-contagious chronic inflammatory
skin disorder of unknown cause. The disorder is a chronic recurring
condition which 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. 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. An
estimated 125 million people worldwide have psoriasis. To learn more
about the role of PDE4 in inflammatory diseases, go to www.discoverpde4.com.
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 our Annual Report
on Form 10-K and other reports filed with the Securities and Exchange
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