The statistical significance for the primary endpoint of PASI 75 at week 16 was achieved for patients receiving Apremilast 30 mg BID monotherapy in both the ESTEEM 1 and 2 phase III studies.
ESTEEM 1 and 2 are the two pivotal phase III, randomized, placebo-controlled studies evaluating Apremilast in patients with moderate to severe chronic plaque psoriasis.
Patients on Apremilast also achieved a statistically significant benefit over placebo in the major secondary endpoint, Static Physician Global Assessment ( sPGA ).
The phase III safety and tolerability data are improved over previously observed phase II psoriasis data and consistent with results from the phase III psoriatic arthritis trials. The overall psoriasis safety database includes nearly 2,000 patients to date. ESTEEM 1 and 2 are ongoing trials. Subjects are being evaluated for safety and efficacy in the long-term extension studies for up to an additional four years. Approximately one-third of the study population was treatment-naïve and two-thirds had prior exposure to either systemic and/or phototherapy; approximately one-third of the overall study population had prior biologic therapy.
ESTEEM 1 and 2 are two pivotal phase III randomized, placebo-controlled study evaluating Apremilast in subjects with a diagnosis of moderate to severe chronic plaque psoriasis for at least 12 months prior to the screening, and at baseline, and who are also a candidate for phototherapy and/or systemic therapy. Approximately 1,250 patients were randomized 2:1 to receive either Apremilast 30 mg BID or placebo for the first 16 weeks, followed by a maintenance phase from weeks 16-32 in which placebo subjects were switched to Apremilast 30 mg BID through week 32, and a randomized withdrawal phase for responders from week 32-week 52 based on their initial randomization and PASI response.
Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4 ( PDE4 ), 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 elevates intracellular cAMP levels, which in turn down-regulates the inflammatory response by modulating the expression of TNF-alfa, IL-23, and other inflammatory cytokines. Elevation of cAMP also increases other anti-inflammatory cytokines such as IL-10.
Psoriasis is an immune-mediated, non-contagious chronic inflammatory skin disorder of unknown cause. The disorder is a chronic recurring condition which varies in severity from minor localized patches to complete body coverage. Plaque psoriasis is the most common type of psoriasis. About 80% of people who develop psoriasis have plaque psoriasis, which appears as patches of raised, reddish skin covered by silvery-white scales. These patches, or plaques, frequently form on the elbows, knees, lower back, and scalp. Psoriasis occurs nearly equally in males and females. Recent studies show that there may be an ethnic link. Psoriasis is believed to be most common in Caucasians and slightly less common in other ethnic groups. Worldwide, psoriasis is most common in Scandinavia and other parts of northern Europe. About 10 to 30% of patients with psoriasis also develop a condition called psoriatic arthritis, which causes pain, stiffness and swelling in and around the joints. ( Xagena )
Source: Celgene, 2013