ME Newswire / Business Wire
SUMMIT, N.J - Monday, March 24th 2014
OTEZLA
demonstrated stable improvements in PASI response up to week 52 in
ESTEEM 1 OTEZLA significantly improved signs and symptoms of psoriasis,
including scalp and nails, compared with placebo in ESTEEM 2 at week 16,
consistent with previously-reported ESTEEM 1 data Long term safety and
tolerability profile in ESTEEM 1 was consistent with previously-reported
long-term data from OTEZLA clinical trial programs No clinically
meaningful changes in laboratory measurements compared with placebo
observed in ESTEEM 1 or 2
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 encouraging.”
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, exposure-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 any country.
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) 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.
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.
INDICATION AND IMPORTANT SAFETY INFORMATION FOR ADULTS WITH PSORIATIC ARTHRITIS
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 Psoriasis
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.
About Celgene
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 Corporation
Investors:
Patrick E. Flanigan III, 908-673-9969
Vice President, Investor Relations
Media:
Catherine Cantone, 732-564-3592
Director, Corporate Communications
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