Celgene Corp (SUMMIT, New Jersey), an integrated global pharmaceutical company, announced positive clinical data from a phase II study of apremilast (CC-10004), its lead orally bioavailable, small molecule inhibitor of TNF/PDE4, in patients with moderate-to-severe plaque psoriasis.

Previously reported results from the 260 patient, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose comparison study demonstrated that 24% of psoriasis patients receiving 20 mg of oral apremilast twice-daily (BID) achieved >e;75% reduction in their baseline Psoriasis Area and Severity Index (PASI 75) score after 84 days (P = .023), compared with a 10% reduction in baseline for placebo patients. Patients achieving >e;50% reduction in their baseline PASI score represented 57% of patients in the apremilast arm (P <.001) compared with 23% of patients in the placebo arm. Those patients achieving >e;90% reduction represented 14% in the apremilast arm (P = .113) compared with 5.7% in the placebo arm. The PASI 90 response for the compound is comparable to Enbrel® (etanercept, Amgen/Wyeth Pharmaceuticals) 25 mg by subcutaneous injection twice-weekly. Patients receiving CC-10004 continued to improve throughout the 12-week treatment regimen.

Newly reported results demonstrated that patients in the 20 mg BID apremilast arm achieved a mean improvement in their Dermatology Life Quality Index (DLQI) score of 7 points (P <.001) compared with 2.7 points in the placebo arm. An improvement of >e;5 points is considered clinically meaningful. Apremilast was found safe and well-tolerated, with no serious infections, deaths, or serious adverse events reported.

Based on these results, Celgene is expanding both the dosing level of apremilast up to 30 mg BID and the dosing duration up to 6 months. Additionally, the company is accelerating its clinical and regulatory strategies for the agent in psoriasis and psoriatic arthritis, and is embarking on exploratory clinical trials in rheumatoid arthritis, rheumatic, dermatologic, and inflammatory diseases.

Apremilast is a member of a proprietary pipeline of novel small molecules with anti-inflammatory activities that impedes the production of multiple pro-inflammatory mediators by inhibiting PDE4 resulting in reductions in TNF-α as well as interleukin (IL)-2, IL-17, IL-23, interferon-gamma, leukotrienes, and nitric oxide synthase. Celgene's second oral PDE4 inhibitor, CC-11050, which has completed phase I trials, may also prove to be effective in a number of inflammatory conditions and the company is moving forward with that compound's development.