Apremilast and PsA – Phase III Results Robustly Positive

Apremilast, the novel oral small-molecule phosphodiesterase4 (PDE4) inhibitor for psoriatic arthritis (PsA), may be one step closer to FDA approval with the release of new phase III clinical trial results at the 2013 annual meeting of the European League Against Rheumatism (EULAR) in Madrid, Spain.

The 52-week safety and efficacy results for 336 patients in the PALACE 1 trial show response rates at the ACR20 (20% improvement) level in up to 65% of patients on apremilast, reports principal investigator Arthur F. Kavanaugh MD, adding that "rheumatologists are excited about having additional therapeutic options for their patients with PsA.” Dr. Kavanaugh is professor of clinical medicine at the University of California-San Diego and Director of the Center for Innovative Therapy (CIT).
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PALACE 1 initially randomized 504 patients who had previously been treated with DMARDs and/or biologic agents to 20 mg or 30 mg of apremilast or an identical-appearing placebo twice a day for 24 weeks. Patients on placebo were re-randomized to 20 mg or 30 mg of the experimental drug at 16 weeks if they showed less than a 20% reduction in swollen/tender joints. At 24 weeks, all remaining placebo patients were re-randomized to 20 mg or 30 mg of apremilast. Patients initially randomized to the drug remained on their original dose.

By weeks 26 and 28, 31.3% of patients on the 20 mg dose and 40% of those on the 30 mg dose had reached ACR20, compared to 19.4% of placebo patients.

By week 52, all patients had had a minimum 28 weeks of exposure to apremilast. Exposure-adjusted incidence rates for adverse events (AEs), severe AEs, and serious AEs are comparable between 0-24 and 0-52 weeks, highlighting the "overall good tolerability of therapy," Kavanaugh says. 

There was a "low incidence" of AEs after 24 weeks, predominantly GI disturbances such as diarrhea, nausea, and vomiting. One death was reported during the first 24 weeks but no safety signals with respect to major cardiac events, malignancies, or opportunistic infections. For exposures up to 52 weeks there were no clinically meaningful laboratory findings, nor any reports of lymphoma, tuberculosis, or tuberculosis reactivations.

PALACE 1 is one of a number of randomized, placebo-controlled trials of apremilast, which modulates a network of pro- and anti-inflammatory mediators in PsA and inhibits PDE4, a cyclic adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory cells.