Third phase III study with OTEZLA to
demonstrate statistically significant improvements versus placebo
for the primary and key secondary endpoints at week 16
More patients achieved a PASI-75 response at
week 32 than at week 16 for those randomized to OTEZLA at baseline
and those switched from etanercept to OTEZLA at week 16
In a post-hoc analysis of PASI-75 at week 16,
there was no statistically significant difference between OTEZLA
and etanercept
No new safety signals identified through week
32 for OTEZLA
Celgene Corporation (NASDAQ:CELG) today announced that results
from its ongoing phase III LIBERATE trial evaluating Otezla®
(apremilast), the Company’s oral, selective inhibitor of
phosphodiesterase 4 (PDE4), in patients with moderate to severe
plaque psoriasis were presented at a late-breaker presentation at
the 73rd Annual Meeting of the American Academy of Dermatology
(AAD) in San Francisco, California.
The LIBERATE study evaluated the clinical efficacy and safety of
either oral OTEZLA 30 mg twice daily or weekly subcutaneous (SC)
etanercept 50 mg compared with placebo at week 16 in 250 patients
who had no prior exposure to a biological therapy. It also examined
the relative safety of a switch from etanercept to OTEZLA after
week 16.
At week 16, patients receiving OTEZLA 30 mg twice daily
demonstrated statistically significant and clinically meaningful
improvement when compared with placebo, as measured by the
Psoriasis Area and Severity Index (PASI)-75 response [primary
endpoint; 40 percent with OTEZLA (n=33/83), 12 percent with placebo
(n=10/84), P<0.0001]. At week 16, statistical significance was
also achieved for patients receiving weekly injections of
etanercept 50 mg when compared with placebo [48 percent with
etanercept (n=40/83), 12 percent with placebo (n=10/84),
P<0.0001].
A post-hoc analysis revealed no significant difference between
OTEZLA and etanercept (P=0.2565) in PASI-75 at week 16. LIBERATE
was not designed or powered to directly compare OTEZLA to
etanercept.
Treatment with OTEZLA also resulted in statistically significant
and clinically meaningful improvement versus placebo at week 16 in
secondary endpoints, including static physician global assessment
(sPGA) of clear or almost clear and Dermatology Quality of Life
Index (DLQI) score change.
Among patients randomized to OTEZLA at baseline, more patients
achieved a PASI-75 response at week 32 than at week 16 [53 percent
(n=44/83) vs. 40 percent (n=33/83), respectively]. Among patients
who switched from etanercept to OTEZLA at week 16, more patients
achieved a PASI-75 response at week 32 than at week 16 [61 percent
(n=51/83) vs. 48 percent (n=40/83), respectively].
The safety and tolerability data for OTEZLA observed in the
LIBERATE study were consistent with previously reported data from
six other phase III studies of OTEZLA in psoriatic arthritis or
psoriasis; no new safety signals were observed. Adverse events
reported in at least five percent of patients taking OTEZLA in the
LIBERATE study were diarrhea, nausea, vomiting and headache
(including tension headache). No new safety or tolerability issues
were observed between weeks 16 and 32 in patients who switched from
etanercept to OTEZLA at week 16.
“Nearly half of psoriasis patients are not satisfied with their
current treatment,” said Kristian Reich, M.D., SCIderm Research
Institute and Dermatologikum Hamburg, Germany. “The positive
results from a third OTEZLA phase III psoriasis trial demonstrating
efficacy and consistent safety of OTEZLA through 32 weeks further
supports the potential for this therapy to have an impact on the
needs of patients suffering from this chronic and debilitating
disease.”
The LIBERATE study is ongoing.
About LIBERATE™
LIBERATE (PSOR-010; EvaLuatIon from a PlaceBo-controllEd Study
of ORal ApremilasT and Etanercept in Plaque Psoriasis) is a phase
IIIb, multicenter, randomized, placebo-controlled, double-blind,
double-dummy study of the efficacy and safety of OTEZLA, etanercept
and placebo, in subjects with moderate to severe plaque psoriasis.
The primary objective of the LIBERATE study was to evaluate the
clinical efficacy and safety of oral OTEZLA 30 mg twice daily
compared with placebo at week 16. Secondary objectives of the study
included: the evaluation of the clinical efficacy and safety of
etanercept 50 mg SC once weekly (QW) compared with placebo at week
16 and the evaluation of the relative safety of a crossover from
etanercept to OTEZLA 30 mg twice daily, as compared with OTEZLA
dosed since week 0, after week 16. Subjects were required to have
inadequate response, intolerance or contraindication to at least
one conventional systemic agent and no prior exposure to biologics.
The study enrolled 250 subjects who were randomized 1:1:1 to
receive OTEZLA 30 mg twice daily, etanercept 50 mg QW or placebo,
for 16 weeks. Following the first 16 weeks, all subjects were
switched to (or continued on) OTEZLA 30 mg twice daily through week
104. The primary endpoint was the proportion of subjects with
either OTEZLA 30 mg twice daily or placebo who achieved PASI-75 at
week 16. Secondary endpoints included other measures of disease
activity and quality of life for the comparison of OTEZLA 30 mg
twice daily versus placebo and the comparison of etanercept 50 mg
SC QW versus placebo.
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 which is
thought to indirectly modulate the production of inflammatory
mediators. The specific mechanism(s) by which OTEZLA exerts its
therapeutic action in patients with psoriasis or psoriatic
arthritis is not well defined.
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 and on September 23, 2014 for the treatment of
patients with moderate to severe plaque psoriasis who are
candidates for phototherapy or systemic therapy. OTEZLA was also
approved on January 16, 2015 by the European Commission (EC) in two
therapeutic indications:
- For the treatment of moderate-to-severe
chronic plaque psoriasis in adult patients who failed to respond to
or who have a contraindication to, or are intolerant to other
systemic therapy including cyclosporine, methotrexate or psoralen
and ultraviolet-A light (PUVA)
- Alone or in combination with Disease
Modifying Antirheumatic Drugs (DMARDs), for the treatment of active
psoriatic arthritis (PsA) in adult patients who have had an
inadequate response or who have been intolerant to a prior DMARD
therapy
Important Safety Information (based on US labeling)
Contraindications
Otezla® (apremilast) 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, 1.3%
(12/920) of patients treated with OTEZLA reported depression
compared to 0.4% (2/506) on placebo; 0.1% (1/1308) of OTEZLA
patients discontinued treatment due to depression compared with
none on placebo (0/506). Depression was reported as serious in 0.1%
(1/1308) of patients exposed to OTEZLA, compared to none in
placebo-treated patients (0/506). Suicidal behavior was observed in
0.1% (1/1308) of patients on OTEZLA, compared to 0.2% (1/506) on
placebo. One patient treated with OTEZLA attempted suicide; one
patient on placebo committed suicide.
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% occurred in 12%
(96/784) of patients treated with OTEZLA and in 5% (19/382) of
patients treated with placebo. Body weight loss of ≥10% occurred in
2% (16/784) of patients treated with OTEZLA compared to 1% (3/382)
of patients treated with 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 ≥5% of patients were (OTEZLA%,
placebo%): diarrhea (17, 6), nausea (17, 7), upper respiratory
tract infection (9, 6), tension headache (8, 4), and headache (6,
4).
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. 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. Follow Celgene on Twitter @Celgene, and on
Pinterest and LinkedIn.
OTEZLA® is a registered trademark and LIBERATE™ is a trademark
of Celgene Corporation. All other trademarks are the property of
their respective owners.
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.
CelgeneInvestors:Patrick E. Flanigan III, 908-673-9969Vice
President, Investor RelationsorMedia:Catherine Cantone,
732-564-3592Director, Corporate Communications
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