|[July 09, 2014]
Celgene Reports Results from the Phase III POSTURE Study Evaluating Oral OTEZLA® in Ankylosing Spondylitis
SUMMIT, N.J. --(Business Wire)--
Celgene Corporation (NASDAQ:CELG) today announced results of its phase
III POSTURE study evaluating OTEZLA, the company's oral, selective
inhibitor of phosphodiesterase 4 (PDE4), in patients with active
ankylosing spondylitis. The OTEZLA arms did not achieve statistically
significant improvement versus the placebo arm for the primary endpoint,
the percentage of patients who achieve an ASAS (Assessment of
SpondyloArthritis international Society) 20 response at week 16.
However, in a prespecified analysis, meaningful efficacy was observed at
Week 24 in a large subset of patients with early-stage disease.
Evaluation of the efficacy results is ongoing.
An independent data monitoring committee (DMC) recommended that the
study proceed unchanged, based on an assessment of the safety and
efficacy data at week 24. According to the protocol, magnetic resonance
imaging (MRI) data will be collected in a subgroup of subjects at week
52 and at additional time points, and radiographs will be taken on all
study patients at week 104 and at additional time points.
The safety and tolerability data observed in the POSTURE study are
consistent with previously reported phase II data in ankylosing
spondylitis, as well as six phase III studies of OTEZLA in psoriatic
arthritis or psoriasis. No new safety signals were observed.
"We are encouraged by these preliminary results, especially in patients
with shorter disease duration and based on our evaluation and learnings
from POSTURE, we plan to initiate another Phase III trial pending
further data analysis, including the 52-week MRI data," said Scott
Smith, Global Head of Inflammation & Immunology at Celgene Corporation.
"Ankylosing spondylitis is a chronic, debilitating disease, and despite
advances over the last 15 years, there remains significant unmet need
for a safe, effective, oral therapy-especially for patients early in the
progression of their disease."
The evaluation of safety and efficacy in the treatment arms is ongoing
and the results of the study will be presented at an upcoming medical
These results are from an investigational phase III study. OTEZLA is not
approved for the treatment of patients with ankylosing spondylitis in
POSTURE is a phase III, multicenter, randomized, double-blind,
placebo-controlled, parallel-group study to evaluate the efficacy and
safety of OTEZLA (apremilast), the Company's oral, selective inhibitor
of phosphodiesterase 4 (PDE4), in the treatment of active ankylosing
spondylitis. The primary endpoint of the study is the proportion of
subjects in each treatment group who achieve an ASAS (Assessment
international Society) 20 response, defined
as an improvement for patients of at least 20%, at week 16. Secondary
endpoints include other measures of function, disease activity, and
quality of life. In POSTURE, 490 subjects were randomized in a 1:1:1
ratio to receive either apremilast 20 mg BID, apremilast 30 mg BID, or
identically-appearing placebo for 24 weeks, with a subsequent long-term
extension phase in which all subjects are treated with apremilast. The
POSTURE study includes adult subjects who have a diagnosis of "definite
AS" as defined by the modified New York criteria (1984); have symptoms
of active disease based on a Bath Ankylosing Spondylitis Disease
Activity Index (BASDA) score of = 4; and have a Total Back Pain
Numerical Rating Scales (NRS) score of =4. Subjects can take
nonsteroidal anti-inflammatory drug (NSAID) therapies, disease-modifying
anti-rheumatic drugs (DMARDs) or low-dose corticosteroids, as long as
they are on a stable dose of these agents prior to baseline and remain
on these agents at the same doses through the 24-week placebo-controlled
phase. Subjects must not have prior treatment with a tumor necrosis
factor (TNF) blocker or any biologic treatment for AS.
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. 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 combined
psoriatic arthritis/psoriasis Marketing Authorization Application (MAA)
in Europe was submitted to health authorities in the fourth quarter of
2013. To learn more about OTEZLA visit www.otezla.com.
IMPORTANT SAFETY INFORMATION
OTEZLA® (apremilast) is indicated for the treatment of adult patients
with active psoriatic arthritis.
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.
Celgene Corporation, headquartered in Summit, New Jersey, is an
integrated global biopharmaceutical company engaged primarily in the
discovery, development and commercialization of novel therapies for the
treatment of cancer and inflammatory diseases through gene and protein
regulation. For more information, please visit www.celgene.com.
Follow us on Twitter (News - Alert) @Celgene as well.
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
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