Celgene Corporation has announced that results from its ongoing phase III LIBERATE trial evaluating Otezla® (apremilast), the Company's oral, selective inhibitor of phosphodiesterase 4 (PDE4), in patients with moderate to severe plaque psoriasis were presented at a late-breaker presentation at the 73rd Annual Meeting of the American Academy of Dermatology (AAD) in San Francisco, California.
The LIBERATE study evaluated the clinical efficacy and safety of either oral OTEZLA 30 mg twice daily or weekly subcutaneous (SC) etanercept 50 mg compared with placebo at week 16 in 250 patients who had no prior exposure to a biological therapy. It also examined the relative safety of a switch from etanercept to OTEZLA after week 16.
At week 16, patients receiving OTEZLA 30 mg twice daily demonstrated statistically significant and clinically meaningful improvement when compared with placebo, as measured by the Psoriasis Area and Severity Index (PASI)-75 response [primary endpoint; 40 percent with OTEZLA (n=33/83), 12 percent with placebo (n=10/84), P
A post-hoc analysis revealed no significant difference between OTEZLA and etanercept (P=0.2565) in PASI-75 at week 16. LIBERATE was not designed or powered to directly compare OTEZLA to etanercept. Treatment with OTEZLA also resulted in statistically significant and clinically meaningful improvement versus placebo at week 16 in secondary endpoints, including static physician global assessment (sPGA) of clear or almost clear and Dermatology Quality of Life Index (DLQI) score change.
Among patients randomized to OTEZLA at baseline, more patients achieved a PASI-75 response at week 32 than at week 16 [53 percent (n=44/83) vs. 40 percent (n=33/83), respectively]. Among patients who switched from etanercept to OTEZLA at week 16, more patients achieved a PASI-75 response at week 32 than at week 16 [61 percent (n=51/83) vs. 48 percent (n=40/83), respectively].
The safety and tolerability data for OTEZLA observed in the LIBERATE study were consistent with previously reported data from six other phase III studies of OTEZLA in psoriatic arthritis or psoriasis; no new safety signals were observed. Adverse events reported in at least five percent of patients taking OTEZLA in the LIBERATE study were diarrhea, nausea, vomiting and headache (including tension headache). No new safety or tolerability issues were observed between weeks 16 and 32 in patients who switched from etanercept to OTEZLA at week 16.
"Nearly half of psoriasis patients are not satisfied with their current treatment," said Kristian Reich, M.D., SCIderm Research Institute and Dermatologikum Hamburg, Germany. "The positive results from a third OTEZLA phase III psoriasis trial demonstrating efficacy and consistent safety of OTEZLA through 32 weeks further supports the potential for this therapy to have an impact on the needs of patients suffering from this chronic and debilitating disease."
The LIBERATE study is ongoing.
LIBERATE (PSOR-010; EvaLuatIon from a PlaceBo-controllEd Study of ORal ApremilasT and Etanercept in Plaque Psoriasis) is a phase IIIb, multicenter, randomized, placebo-controlled, double-blind, double- dummy study of the efficacy and safety of OTEZLA, etanercept and placebo, in subjects with moderate to severe plaque psoriasis. The primary objective of the LIBERATE study was to evaluate the clinical efficacy and safety of oral OTEZLA 30 mg twice daily compared with placebo at week 16. Secondary objectives of the study included: the evaluation of the clinical efficacy and safety of etanercept 50 mg SC once weekly (QW) compared with placebo at week 16 and the evaluation of the relative safety of a crossover from etanercept to OTEZLA 30 mg twice daily, as compared with OTEZLA dosed since week 0, after week 16. Subjects were required to have inadequate response, intolerance or contraindication to at least one conventional systemic agent and no prior exposure to biologics. The study enrolled 250 subjects who were randomized 1:1:1 to receive OTEZLA 30 mg twice daily, etanercept 50 mg QW or placebo, for 16 weeks. Following the first 16 weeks, all subjects were switched to (or continued on) OTEZLA 30 mg twice daily through week 104. The primary endpoint was the proportion of subjects with either OTEZLA 30 mg twice daily or placebo who achieved PASI-75 at week 16. Secondary endpoints included other measures of disease activity and quality of life for the comparison of OTEZLA 30 mg twice daily versus placebo and the comparison of etanercept 50 mg SC QW versus placebo.