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Positive Results Reported From Late-Stage Study of Brodalumab (AMG 827) in Patients With Plaque Psoriasis
A phase III study evaluating the human monoclonal antibody brodalumab (AMG 827, Amgen/AstraZeneca) in patients with moderate-to-severe plaque psoriasis met all primary and secondary endpoints for both evaluated doses (140 mg and 210 mg).
The AMAGINE-1 trial was one of three phase III studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. AMAGINE-2 and AMAGINE-3 are designed to evaluate the efficacy and safety of induction and maintenance regimens of brodalumab at different dose schedules in patients with moderate-to-severe plaque psoriasis compared with ustekinumab and placebo.
AMAGINE-1 assessed the safety and efficacy of brodalumab compared with placebo in patients with moderate-to-severe plaque psoriasis. Another objective of the study was to assess safety and efficacy when patients who responded to treatment with brodalumab began receiving placebo compared with patients who continued receiving brodalumab.
The phase II trial began with a 12-week, double-blind, placebo-controlled induction phase. During this phase, patients were randomly assigned to receive a subcutaneous injection of brodalumab (140 mg or 210 mg) or placebo every 2 weeks.
At week 12, patients originally assigned to receive brodalumab who achieved clear or almost clear skin, according to their static Physician Global Assessment (sPGA) score (0 or 1), were randomly assigned to receive placebo or to continue treatment with brodalumab at the current dose. Re-assigned patients losing disease control were treated with their original brodalumab dose. All patients originally assigned to receive placebo and any patient not qualifying for re-assignment (sPGA > 1) received brodalumab 210 mg every 2 weeks.
The trial’s primary endpoints were the proportion of patients achieving at least a 75% improvement from baseline in disease severity at week 12, as measured by the Psoriasis Area Severity Index (PASI 75), and the proportion of patients achieving clear or almost clear skin at week 12, as measured by the sPGA.
Of the 661 patients enrolled in the study, 46.0% reported prior biologic use, and 28.7% weighed more than 100 kg at baseline (mean weight for the study population: 90.8 kg).
A significantly higher proportion of patients treated with brodalumab achieved a PASI 75 response (primary endpoint) as well as PASI 90 and PASI 100 responses at week 12 (secondary endpoints) compared with placebo. The results showed that 83.3% of patients in the 210-mg group and 60.3% of patients in the 140-mg group achieved PASI 75 responses compared with 2.7% of the placebo group.
The results also showed that 70.3% of patients in the 210-mg group and 42.5% of patients in the 140-mg group achieved PASI 90 responses compared with 0.9% of the placebo group. Further, 41.9% of patients in the 210-mg group and 23.3% of patients in the 140-mg group achieved PASI 100 responses compared with 0.5% of the placebo group.
The most common adverse events that occurred during the placebo-controlled period in brodalumab-treated patients included included nasopharyngitis, upper respiratory tract infection, and headache. Serious adverse events occurred in 1.8% of patients in the 210-mg group and in 2.7% of patients in the 140-mg group compared with 1.4% of the placebo group during the placebo-controlled period.
Brodalumab is a human monoclonal antibody that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 ligands to the receptor. By stopping IL-17 ligands from activating the receptor, brodalumab prevents the body from receiving signals that may lead to inflammation. The IL-17 pathway plays a central role in inducing and promoting inflammatory disease processes.
In addition to the phase III trial in patients with moderate-to-severe plaque psoriasis, brodalumab is being investigated for the treatment of psoriatic arthritis in a phase III study and for the treatment of asthma in a phase II trial.
Source: Amgen; May 9, 2014.