SILVER SPRING, MD. – The human monoclonal antibody secukinumab is expected to be the first biologic that targets interleukin-17A to be approved by the agency for treating psoriasis, with a Food and Drug Administration advisory panel’s unanimous support for the approval.
At a meeting on Oct. 20, the FDA’s Dermatologic and Ophthalmic Drugs Advisory committee voted 7-0 to recommend approval of secukinumab for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy, the indication proposed by Novartis Pharmaceuticals. Secukinumab “selectively binds and neutralizes” IL-17A, a proinflammatory cytokine “that is involved in normal inflammatory and immune responses and plays a key role in the pathogenesis of plaque psoriasis,” according to the company.
If approved, secukinumab would be the first IL-17A blocker available and would be available in a lyophilized formulation for reconstitution, and in a liquid formulation in a refilled syringe or autoinjector pen. The 300-mg dose was determined to be the best dose to achieve clear or almost clear skin, with a favorable safety profile that was comparable to that of the 150-mg dose, which was also studied in phase II and III studies, according to Novartis. The company has proposed a dose of 300 mg, administered with a subcutaneous injection, at 0, 1, 2, 3, and 4 weeks, followed by 300 mg once a month.
The panel agreed that the 300-mg dose was effective with an acceptable risk-benefit profile, but agreed that it would be useful to have the 150-mg dose, which was also effective in trials, be available as well. The panel also recommended that the 450-mg dose, which was not formally studied, be evaluated further in postmarketing studies, because it could be useful in nonresponders and for heavier patients weighing 90 kg (about 198 pounds) or more, because of evidence that the 300-mg dose was less effective in heavier patients.
Secukinumab has been studied in 10 phase II and III studies of almost 4,000 patients with psoriasis. In the two main phase III studies, the 150-mg and 300-mg doses were compared with placebo (and to a formulation of etanercept not available in the United States in one study); the primary endpoints were the Psoriasis Area and Severity Index (PASI) 75, a 75% improvement of psoriasis from baseline, and an Investigator Global Assessment (IGA) score of 0 or 1 (clear or almost clear skin).