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Pivotal Phase III Data Reported for Psoriasis Drug Apremilast
Statistical significance for the primary endpoint — a 75% reduction in the Psoriasis Area and Severity Index (PASI 75) at week 16 — was achieved for patients receiving apremilast 30 mg twice daily versus placebo in both the ESTEEM 1 and ESTEEM 2 phase III trials. ESTEEM 1 and 2 are the two pivotal phase III, randomized, placebo-controlled studies evaluating apremilast (Celgene), an oral small-molecule inhibitor of phosphodiesterase 4 (PDE4), in patients with moderate to severe chronic plaque psoriasis.
Patients treated with apremilast also achieved a statistically significant benefit versus placebo in the Static Physician Global Assessment (sPGA) — the studies’ major secondary endpoint.
A new drug application (NDA) for psoriasis, based on the ESTEEM 1 and 2 data, is expected in the second half of 2013.
The ESTEEM trials evaluated apremilast in patients who had moderate to severe chronic plaque psoriasis for at least 12 months prior to screening, and who were candidates for phototherapy and/or systemic therapy. A total of approximately 1,250 patients were randomly assigned to receive either apremilast 30 mg twice daily or placebo for the first 16 weeks. This initial treatment phase was followed by a maintenance phase lasting from week 16 to week 32, in which the placebo-treated patients were switched to apremilast 30 mg twice daily through week 32, and by a randomized withdrawal phase for responders lasting from week 32 to week 52, based on their initial randomization and PASI response.
Apremilast, a 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. The inhibition of PDE4 increases intracellular cAMP levels, which in turn down-regulates the inflammatory response by modulating the expression of tumor necrosis factor (TNF)-alpha, interleukin (IL)-23, and other inflammatory cytokines. Elevation of cAMP also increases other anti-inflammatory cytokines, such as IL-10.
Source: Celgene; January 7, 2013.