Apremilast Meets Primary Endpoint in Phase III Psoriasis Trial
Drug significantly more effective than placebo in chronic plaque psoriasis (Mar. 2)
Positive results from the ESTEEM 1 trial — a phase III study of apremilast (Celgene Corporation) in patients with chronic plaque psoriasis — were reported at the annual meeting of the American Academy of Dermatology, held in Miami, Florida. Apremilast is an oral small-molecule inhibitor of phosphodiesterase-4 (PDE4).
The ESTEEM 1 trial evaluated the efficacy and safety of apremilast in a range of patients. Approximately one-third of the study population was systemic and/or phototherapy treatment-naïve. Nearly 30% percent of the overall study population had prior biologic therapy, which included biologic failures.
In the ESTEEM 1 study, a significantly higher percentage of apremilast-treated patients demonstrated a 75% reduction on the Psoriasis Area and Severity Index (PASI-75) at week 16 compared with placebo-treated patients (33.1% vs. 5.3%, respectively; P < 0.0001). Significantly higher PASI-75 scores at week 16 were demonstrated across all patient groups enrolled in the study, including systemic-naïve and biologic-naïve patients receiving apremilast 30 mg twice daily compared with placebo (38.7% vs. 7.6%; P < 0.0001 and 35.8% vs. 5.9%; P < 0.0001, respectively). Apremilast demonstrated maintenance of effect over time, as measured by the mean percent change from baseline in the PASI score over 32 weeks, with apremilast demonstrating a 54.9% reduction at week 16 and a 61.9% reduction at week 32.
Statistical significance at week 16 was also demonstrated in the major secondary endpoint, the Static Physician Global Assessment (sPGA) of “clear” or “almost clear” (P < 0.0001), and in other key secondary endpoints, as well as in assessments of difficult-to-treat areas (i.e., nail and scalp psoriasis).
Apremilast was generally well tolerated. The most common adverse events (AEs) with an incidence greater than that of the placebo group were diarrhea, nausea, and headache. More than 96% of the patients in the study reported no AEs or mild-to-moderate AEs. Similar percentages of patients reported both serious AEs and severe AEs in the group treated with apremilast 30 mg twice daily compared with the placebo group (2.1% vs. 2.8% and 3.6% vs. 3.2%, respectively).
Apremilast, an oral small-molecule PDE4 inhibitor, works intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators. PDE4 is a cyclic adenosine monophosphate (cAMP)-specific PDE and the dominant PDE in inflammatory cells. PDE4 inhibition increases intracellular cAMP levels, which in turn down-regulates the inflammatory response by modulating the expression of tumor necrosis factor-alpha (TNF-alpha), interleukin-23 (IL-23), and other inflammatory cytokines. Elevation of cAMP also increases anti-inflammatory cytokines, such as IL-10.
A new drug application (NDA) for apremilast is expected to be submitted to the FDA in the second half of 2013.
Source: Celgene; March 2, 2013.