Phase III POSTURE Study Did Not Achieve Primary Endpoint of ASAS 20 at Week 16
Based on Efficacy and Safety Data at Week 24, the Independent Data Monitoring Committee Recommended Continuation of the Phase III POSTURE Study Without Change
In OTEZLA Study Arms, ASAS 20 Results Continued to Improve Over Time
OTEZLA Tolerability and Safety Profile Consistent With Previous Clinical Trials
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
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 meeting.
These results are from an investigational phase III study. OTEZLA is not approved for the treatment of patients with ankylosing spondylitis in any country.
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
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
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 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
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.
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results or outcomes may differ materially from those implied by the
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