Positive Results Reported for Psoriasis Drug Secukinumab in Phase III Trials
Data show superiority over etanercept
Positive results from two pivotal phase III studies evaluating the interleukin-17A (IL-17A) inhibitor secukinumab (Novartis) have been published online in the New England Journal of Medicine.
Secukinumab met all primary and key secondary endpoints at week 12 in the ERASURE and FIXTURE trials, demonstrating superiority over etanercept (Enbrel, Amgen) in improving moderate-to-severe plaque psoriasis symptoms in the FIXTURE study, and superiority over placebo in both studies.
More than half of patients treated with secukinumab 300 mg experienced clear (Psoriasis Area and Severity Index [PASI] 100) or almost clear (PASI 90) skin by week 12 (59.2% in the ERASURE trial and 54.2% in the FIXTURE trial; P < 0.001). In comparison, 20.7% of patients treated with etanercept experienced PASI 90 or PASI 100 in the FIXTURE study.
The patients’ response to treatment with secukinumab 300 mg continued to improve from week 12, with more than 70% experiencing clear or almost clear skin by week 16 (72.4% and 36.8% with PASI 90 and PASI 100, respectively) in the FIXTURE study, which was maintained in most patients up to week 52 with continued treatment.
Secukinumab-treated patients also had their symptoms resolve more quickly than did those treated with etanercept in the FIXTURE trial. Clinically relevant differences were observed as early as week 2, and on average patients treated with secukinumab 300 mg had their symptoms halved by week 3, compared with week 7 for etanercept-treated patients.
The ERASURE (Efficacy of Response And Safety of Two Fixed SecUkinumab REgimens in Psoriasis) and FIXTURE (Full-Year Investigative EXamination of Secukinumab vs. ETanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis) studies are part of the largest phase III program in moderate-to-severe plaque psoriasis completed to date, involving more than 3,300 patients in more than 35 countries.
ERASURE and FIXTURE assessed the efficacy, safety, and tolerability of induction-period treatment (at week 12) and maintenance therapy (at week 52) with subcutaneous secukinumab 150 mg or 300 mg in patients with moderate-to-severe plaque psoriasis. Both studies were multicenter, randomized, double-blind, placebo-controlled (FIXTURE: also active-controlled), parallel-group, phase III trials involving 738 patients and 1,306 patients with moderate-to-severe plaque psoriasis, respectively. Each study consisted of a 1- to 4-week screening period, a 12-week induction period, a 40-week maintenance period, and an 8-week follow-up period.
Secukinumab is a fully human monoclonal antibody that selectively binds to and neutralizes IL-17A — a key cytokine (messenger protein) involved in the development of psoriasis. Research has shown that IL-17A plays an important role in driving the body’s autoimmune response in disorders such as moderate-to-severe plaque psoriasis and is a preferred target for investigational therapies.
Regulatory submission for secukinumab in the U.S. was completed in 2013.
Source: Novartis; July 9, 2014.