ME NewsWire/Business Wire
BOUDRY, Switzerland. - Friday, June 13th 2014
Clinically
meaningful improvements in enthesitis, dactylitis and physical function
with OTEZLA seen at week 16 and were sustained for up to 52 weeks of
treatment
PALACE 4 is the first and only large randomized,
placebo-controlled study to examine the efficacy and safety of a single
agent in patients naïve to previous DMARD therapy
Long-term safety and tolerability profile with OTEZLA consistent with previous PALACE studies
EULAR 2014
Celgene
International Sàrl, a wholly-owned subsidiary of Celgene Corporation
(NASDAQ:CELG), today announced results from a long-term (52-week) phase
III trial of OTEZLA, the Company’s oral, selective inhibitor of
phosphodiesterase 4 (PDE4), in psoriatic arthritis patients who have not
had prior treatment with systemic or biologic disease-modifying
antirheumatic drugs (DMARDs). The data were presented at the European
League Against Rheumatism Annual Congress (EULAR 2014) in Paris, France.
“Physicians
need a variety of options to treat psoriatic arthritis, as treatment is
highly individualized and some patients may not be appropriate
candidates for biologics or certain systemic therapies,” said Alvin
Wells, M.D., Ph.D., director, Rheumatology and Immunology Center,
Franklin, MN. “These efficacy and safety results suggest that OTEZLA
monotherapy has the potential to be used for adults with active
psoriatic arthritis in the first-line setting, prior to the initiation
of DMARD therapy, and possibly as a long-term treatment option.”
PALACE 4: 52-week Enthesitis and Dactylitis
Results
demonstrated that treatment with OTEZLA monotherapy in patients with
pre-existing enthesitis (inflammation at sites where tendons or
ligaments insert into bone) or dactylitis (a count of fingers and toes
with inflammation), two key manifestations of psoriatic arthritis,
resulted in long-term improvements. Results were sustained over 52 weeks
in patients initially randomized to OTEZLA monotherapy and completing
52 weeks of the study. At week 52, median Maastricht Ankylosing
Spondylitis Enthesitis Score (MASES) decreased by 75.0 percent and 45.9
percent of patients receiving OTEZLA 30 mg BID achieved a score of 0,
indicating no pain at any of the enthesitis sites assessed. OTEZLA 30 mg
BID also resulted in a median 100 percent decrease in dactylitis count.
A dactylitis count of 0, indicating no signs of dactylitis, was
achieved in 68.8 percent of patients.
PALACE 4: 52-week Physical Function
The
results of a physical function analysis from PALACE 4 demonstrated that
52 weeks of treatment with OTEZLA monotherapy resulted in sustained
improvements for up to 52 weeks, as measured by validated assessment
tools.
In patients who were treated with OTEZLA monotherapy
continuously through 52 weeks, clinically meaningful improvements were
seen at week 16 in the Health Assessment Questionnaire-Disability Index
(HAQ-DI), a key instrument measuring physical function, and improvements
were sustained for up to 52 weeks. HAQ-DI measures the difficulty
patients have performing activities of daily life such as difficulty
dressing, walking and eating.
The HAQ-DI results were further
supported by improvements in the short form health survey version 2
Physical Functioning (SF-36 v2 PF) seen in patients who were treated
with OTEZLA monotherapy continuously through 52 weeks.
PALACE 4: 52-week Safety and Tolerability
Long-term
(52 week) safety results from PALACE 4 identified no new safety
findings for OTEZLA compared with the previously reported 24-week safety
results. Safety results were consistent with previously reported
results from the phase III PALACE 1, 2 and 3 clinical trials.
The
majority of adverse events (AEs) were mild or moderate in severity and
led to a low rate of discontinuation (5.2 percent in all patients
exposed to OTEZLA). The most commonly reported AEs were nausea,
diarrhea, headache and upper respiratory tract infection. 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 and no medical intervention. Serious AEs
occurred at low rates, were comparable across treatment groups (0.6
percent OTEZLA 30 mg BID vs. 2.8 percent placebo) and did not increase
with long-term OTEZLA exposure. The mean weight loss at the end of the
52 week OTEZLA-exposure period was 1.19 kg in OTEZLA 30 mg BID and 0.91
kg in OTEZLA 20 mg BID.
Similar to other OTEZLA data reported from PALACE 1, 2 and 3, these data do not indicate a need for laboratory monitoring.
About PALACE 4
PALACE
4 is a phase III multi-center, double-blind, placebo-controlled,
parallel-group studies with two active-treatment groups. More than 500
DMARD-naïve patients were randomized 1:1:1 to receive either OTEZLA 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 OTEZLA.
The
primary endpoint was the modified American College of Rheumatology
criteria for 20 percent improvement (ACR20) at week 16. Secondary
endpoints included other measures of signs and symptoms of psoriatic
arthritis, physical functioning, and patient-reported outcomes.
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.
About OTEZLA
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.
Important Safety Information
INDICATION
OTEZLA® (apremilast) is indicated for the treatment of adult patients with active psoriatic arthritis.
IMPORTANT SAFETY INFORMATION
Contraindications
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
changes occur.
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 recommended.
Adverse Reactions
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
(2.0, 0.2).
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 woman.
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
Prescribing Information.
Please click here for Full Prescribing Information.
About Psoriatic Arthritis
Psoriatic
arthritis is a painful, chronic inflammatory disease characterized by
pain, stiffness, swelling and tenderness of the joints, inflammation of
specific ligaments and tendons, and decrease in physical functioning. It
is estimated that nearly 38 million people worldwide have psoriatic
arthritis. Psoriatic arthritis can impact day-to-day activities and has
been reported to increase work disability. Common signs and symptoms of
psoriatic arthritis include pain, stiffness, and swelling in joints. To
learn more about psoriatic arthritis, go towww.discoverpsa.com. To learn
more about the role of PDE4 in inflammatory diseases, go to
www.discoverpde4.com.
About Celgene
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.
Forward-Looking Statements
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 Commission.
Contacts
Celgene International Sàrl
Investors:
Patrick E. Flanigan III, 908-673-9969
Vice President, Investor Relations
Media:
Catherine Cantone, 732-564-3592
Director, Corporate Communications
Permalink: http://www.me-newswire.net/news/11322/en
No comments:
Post a Comment