The results from ESTEEM 1 for the treatment of psoriasis were presented at the American Academy of Dermatology annual meeting. ESTEEM 1 evaluated efficacy and safety 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 PASI-75 at week 16 than did placebo patients ( 33.1% vs 5.3%; P less than 0.0001 ). Significantly higher PASI-75 scores at week 16 were demonstrated across all patient segments enrolled in this study, including systemic-naïve and biologic-naïve patients receiving Apremilast 30 mg BID compared with placebo ( 38.7% vs 7.6%; P less than 0.0001 and 35.8% vs 5.9%; P less than 0.0001 respectively ). Apremilast demonstrated maintenance of effect over time, as measured by the Mean Percent Change from Baseline in 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, Static Physician Global Assessment ( sPGA ) of clear or almost clear (P less than 0.0001), and other key secondary endpoints ( change in BSA, Pruritus VAS, DLQI ), as well as in assessments of difficult to treat areas ( nail and scalp psoriasis ).

The overall safety and tolerability profile was consistent with results from previously reported phase III psoriatic arthritis trials. No cases of tuberculosis or lymphoma were observed through week 16, and there was no increased risk of cardiovascular events or serious opportunistic infection. Apremilast was generally well tolerated. The most common adverse events ( AEs ) greater than placebo were diarrhea, nausea and headache. Greater than 96% of patients in the study reported no AEs or mild to moderate adverse events. A similar percentage of patients reported both serious AEs and severe AEs in the Apremilast 30 mg BID treatment group compared to placebo ( 2.1% vs 2.8% and 3.6% vs 3.2%, respectively ).

ESTEEM 1 & 2 are two pivotal phase III randomized, placebo-controlled studies 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 were also candidates 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 Apremilast randomization and PASI response.

Apremilast, an oral small-molecule inhibitor of phosphodiesterase 4 ( PDE-4 ), works intracellularly to modulate a network of pro-inflammatory and anti-inflammatory mediators.

Source: Celgene, 2013

XagenaMedicine2013