Celgene (CELG)'s OTEZLA® Misses Mark In Phase 3 Spinal Arthritis Study
7/9/2014 7:18:47 AM
Celgene Reports Results from the Phase III POSTURE Study Evaluating Oral OTEZLA® in Ankylosing Spondylitis
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
SUMMIT, N.J.--(BUSINESS WIRE)-- Celgene Corporation (NASDAQ:CELG) today announced results of its phase III POSTURE study evaluating OTEZLA, the company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), 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.
"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 Scott Smith, Global Head of Inflammation & Immunology at Celgene Corporation. "Ankylosing spondylitis is a chronic, debilitating disease, and despite advances over the last 15 years, there remains significant unmet need for a safe, effective, oral therapy—especially for patients early in the progression of their disease."
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 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.
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 March 21, 2014 by the U.S. Food and Drug Administration (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. To learn more about OTEZLA visit www.otezla.com.
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 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 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.
Celgene Corporation, headquartered in Summit, New Jersey, is an integrated global biopharmaceutical company engaged primarily in the discovery, development and commercialization of novel therapies for the treatment of cancer and inflammatory diseases through gene and protein regulation. For more information, please visit www.celgene.com. Follow us on Twitter @Celgene as well.
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 our other reports filed with the Securities and Exchange Commission.
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