Date: 2014-07-09
Type of
information: Results
phase: 3
Announcement: results
Company: Celgene (USA - NJ)
Product: Otezla® (apremilast)
Action
mechanism:
- phosphodiesterase 4 inhibitor. Otezla® is an oral, small-molecule, selective inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. Otezla® was approved on March 21, 2014 by the 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.
Disease: ankylosing spondylitis
Therapeutic
area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country:
Trial
details:
- POSTURE is a phase III, multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate the efficacy and safety of Otezla® (apremilast), 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 of SpondyloArthritis 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 New York criteria (1984); have symptoms of active disease based on a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ? 4; and have a Total Back Pain Numerical Rating Scales (NRS) score of ?4. Subjects can take nonsteroidal anti-inflammatory drug (NSAID) therapies, disease-modifying anti-rheumatic drugs (DMARDs) or low-dose corticosteroids, as long as they are on a stable dose of these agents prior to baseline and remain on these agents at the same doses through the 24-week placebo-controlled phase. Subjects must not have prior treatment with a tumor necrosis factor (TNF) blocker or any biologic treatment for AS.
Latest
news:
- • On July 9, 2014, Celgene announced results of its phase III POSTURE study evaluating Otezla® in patients with active ankylosing spondylitis.The Otezla® arms did not achieve statistically significant improvement versus the placebo arm for the primary endpoint, the percentage of patients who achieve an ASAS (Assessment of SpondyloArthritis international Society) 20 response at week 16. However, in a prespecified analysis, meaningful efficacy was observed at Week 24 in a large subset of patients with early-stage disease. Evaluation of the efficacy results is ongoing.
- 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.
- Celgene plans to initiate another Phase III trial pending further data analysis, including the 52-week MRI data. 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.
Is
general: Yes
