SILVER SPRING, MD. — An expert panel has unanimously recommended that ustekinumab, a novel human monoclonal antibody, be approved for treating adults with moderate to severe plaque psoriasis, but said more safety data were necessary about potential long-term risks associated with treatment, particularly malignancies.
At a meeting of the Food and Drug Administration's dermatologic and ophthalmic drugs advisory panel in June, the panel voted 11 to 0 to support approval of ustekinumab, which is made by Centocor Inc.
It also unanimously agreed that more safety data in more patients treated for a longer period of time was critical, and that the potential for malignancy linked to ustekinumab was based on the theoretical risk as well as some animal data indicating an increased carcinogenic risk within the cytokines interleukin-12 (IL-12) and interleu- kin-23 (IL-23), which ustekinumab targets.
Ustekinumab is a first in class new entity that has not been approved for any other indication. The company has proposed that the first two doses of ustekinumab be administered 4 weeks apart, then every 12 weeks during maintenance treatment; it is administered by subcutaneous injection.
Two phase III studies compared two doses of ustekinumab with placebo in almost 2,000 adult patients who had had plaque psoriasis for at least 6 months, with baseline Psoriasis Area Severity Index (PASI) scores of 12 or higher. At 12 weeks, the proportion of patients with a PASI 75 response (at least a 75% improvement in PASI score), the primary efficacy end point, and the proportion who had a physician's global assessment (PGA) of cleared or minimal plaques, a secondary end point, were significantly greater in those on ustemnimab than in those on placebo, according to the FDA.
In one study, 67% of those on the 45-mg dose and 66% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 3% of those on placebo. In the second study, 67% of those on the 45-mg dose and 76% of those on the 90-mg dose achieved a PASI 75 at 12 weeks, compared with 4% of those on placebo. In the studies, the proportion of patients who achieved a PGA of cleared or minimal plaques at 12 weeks ranged from 60% to 73% of those on ustekinumab, compared with 4%–5% in those on placebo.
Because of its mechanism of action, treatment may increase the risk for malignancies, and other adverse events, such as serious infections. In the studies, rates of serious infections and malignancies were low “and consistent with the expected background rates,” said Centocor.
The FDA usually follows its advisory panels' recomendations, which are not binding. Other biologic therapies approved for psoriasis are alefacept (Amevive), efalizumab (Raptiva), infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira).