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
In a post-hoc analysis of
No new safety signals identified through week 32 for OTEZLA
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
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
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
The LIBERATE study is ongoing.
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
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
Important Safety Information (based on US labeling)
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
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.
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.
OTEZLA® is a registered trademark and LIBERATE™ is a trademark of
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
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