Celgene reported Phase III study results Wednesday demonstrating that its oral PDE4 inhibitor Otezla (apremilast) failed to significantly improve symptoms in patients with ankylosing spondylitis (AS) at 16 weeks, compared with placebo, but displayed “meaningful efficacy” at 24 weeks in a “large subset” of patients with early-stage disease. The company said that, based on the data obtained for the longer treatment period, an independent Data Monitoring Committee (DMC) recommended that the trial proceed without any changes.
The POSTURE study involved 490 adults diagnosed with definite AS who had scores of at least 4 for both the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Total Back Pain Numerical Rating Scales (NRS). Participants were randomised to receive one of two doses of Otezla or placebo twice daily for 24 weeks. Patients were permitted to take non-steroidal anti-inflammatory drugs, disease-modifying anti-rheumatic drugs or low-dose corticosteroids, as long as they were on stable doses of the therapies prior to baseline and remained that way throughout the trial, but they could not have had previous treatment with a TNF blocker or any biologic treatment for AS.
The study’s primary endpoint is the proportion of patients achieving at least 20-percent improvement in the Assessment of SpondyloArthritis international Society criteria (ASAS 20 response) at week 16, while secondary objectives include other measures of function, disease activity and quality of life. Celgene indicated that the safety and tolerability data seen in the trial so far are “consistent with previously reported Phase II data in AS, as well as six late-stage studies of Otezla in psoriatic arthritis or psoriasis,” and that no new safety signals were observed. Evaluation of safety and efficacy in the treatment arms is ongoing and results from the study will be presented at an upcoming medical meeting, the company said.
Scott Smith, global head of inflammation and immunology at Celgene, remarked that the drugmaker is “encouraged by these preliminary results, especially in patients with shorter disease duration.” Celgene said that according to the study’s protocol, magnetic resonance imaging (MRI) data will be collected in a subgroup of patients at week 52 and at additional time points, while radiographs will be taken on all patients at week 104 and at additional time points. Smith added that based on the company’s evaluation of the POSTURE study, “we plan to initiate another Phase III trial pending further data analysis, including the 52-week MRI data.”
Otezla was approved by the FDA in March for the treatment of psoriatic arthritis, and Celgene said it filed an EU application in the fourth quarter of last year to market the drug for psoriatic arthritis and psoriasis. The medicine is also being tested as a potential therapy in other indications, including Behçet’s disease, for which Celgene announced positive Phase II study results last year, and Crohn’s disease. The company projects revenue in the range of $1.5 billion to $2 billion for the drug in 2017. For this year, analysts anticipate sales of about $130 million for Otezla (for related analysis, see ViewPoints: Pricing strategy seen as integral to uptake of Celgene’s latest new drug approval).