Amgen and AstraZeneca has announced that AMAGINE-3™, a pivotal, multi-arm Phase 3 trial evaluating two doses of brodalumab in more than 1,800 patients with moderate-to-severe plaque psoriasis, met its primary endpoints when compared with both Stelara (ustekinumab) and placebo at week 12. Brodalumab was shown to be superior to Stelara on the primary endpoint of achieving total clearance of skin disease, as measured by the Psoriasis Area Severity Index (PASI 100). When compared with placebo, a significantly greater proportion of patients treated with brodalumab achieved at least a 75% improvement from baseline in disease severity at week 12, as measured by the Psoriasis Area Severity Index (PASI 75). A significantly greater proportion of patients treated with brodalumab also achieved clear or almost clear skin at week 12 compared with placebo, according to the static Physician Global Assessment (sPGA 0 or 1). All key secondary endpoints comparing brodalumab with Stelara and placebo were also met.
Results showed that 36.7% of patients in the brodalumab 210 mg group, 27.0% of patients in the brodalumab 140 mg group, 18.5% of patients in the Stelara group and 0.3% of patients in the placebo group achieved total clearance of skin disease (PASI 100). In addition, 85.1% of patients in the brodalumab 210 mg group, 69.2% of patients in the brodalumab 140 mg group, 69.3% of patients in the Stelara group and 6.0% of patients in the placebo group achieved PASI 75.
‘Despite a variety of treatment options available for psoriasis, many patients still do not meet skin clearance goals,’ said Sean E. Harper, MD., executive vice president of Research and Development at Amgen. ‘These results are of particular importance as they are the first to demonstrate superiority to Stelara in achieving total skin clearance, and the second positive pivotal Phase 3 study evaluating brodalumab in patients with moderate-to-severe plaque psoriasis.’
The most common adverse events that occurred in the brodalumab arms (more than 5% of patients in either group) were common cold, joint pain, upper respiratory tract infection and headache. Serious adverse events occurred in 1.4% of patients in the 210 mg group and 1.6% of patients in the 140 mg group compared with 0.6% for Stelara and 1.0% for placebo during the placebo-controlled period.
Brodalumab is the only investigational treatment in development that binds to the interleukin-17 (IL-17) receptor and inhibits inflammatory signaling by blocking the binding of several IL-17 cytokines (A, F, A/F and C) to the receptor. The IL-17 receptor and cytokine family play a central role in development and clinical manifestation of plaque psoriasis.
‘These results add to the growing body of evidence supporting the potential value that brodalumab may bring to the treatment of psoriasis by targeting the IL-17 receptor,’ said Briggs W. Morrison, M.D., executive vice president of Global Medicines Development at AstraZeneca. ‘We look forward to sharing results later this year from AMAGINE-2™, our remaining head-to-head study evaluating brodalumab versus Stelara.’
The AMAGINE program is composed of three Phase 3 studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. Top-line results from AMAGINE-1™, designed to assess the efficacy and safety of brodalumab compared with placebo, were released in May 2014. Detailed results from the AMAGINE-3 study will be submitted to the appropriate scientific forum for presentation and/or publication. Results from AMAGINE-2 are expected by year end.
AMAGINE-3 Study Design
AMAGINE-3 is a Phase 3 study that assessed the safety and efficacy of brodalumab given at two doses every 2 weeks via subcutaneous injection compared with placebo and Stelara in patients with moderate-to-severe plaque psoriasis. The study also assessed the safety and efficacy of four maintenance regimens of brodalumab. The primary endpoint comparing brodalumab with Stelara was the proportion of patients achieving total clearance of skin disease, as measured by PASI 100 at week 12. When comparing brodalumab with placebo, the primary endpoints included the proportion of patients achieving at least a 75% improvement from baseline in disease severity (PASI 75) at week 12, and the achievement of clear or almost clear skin, according to the sPGA (0 or 1) at week 12.
The study began with a 12-week, double-blind, active comparator- and placebo-controlled induction phase, where patients were randomized in a 2:2:1:1 ratio to receive brodalumab (210 mg or 140 mg), Stelara (per the labeled dose), or placebo. At week 12, patients originally randomized to either brodalumab arm were re-randomized 2:2:2:1 into the maintenance phase to receive brodalumab 210 mg or 140 mg at four different maintenance regimens. Patients originally randomized to Stelara continued to receive the same treatment, and those originally randomised to receive placebo began 210 mg of brodalumab every 2 weeks.
At week 52, patients entered the long-term extension portion of the study, and those who were originally randomised to receive Stelara began receiving 210 mg of brodalumab every 2 weeks. All other patients continued on treatment with brodalumab at the same dose they were being treated with at week 52. Patients may be enrolled in the study for up to 271 weeks (approximately 5 years).
A PASI score is a measure of psoriatic plaque redness, scaling and thickness and the extent of involvement in each region of the body. Treatment efficacy is often measured by the reduction of PASI from baseline (e.g., a 75% reduction is known as PASI 75, a 90% reduction is known as PASI 90 and PASI 100 is total clearance of skin disease).
sPGA is a physician’s rating of psoriasis severity at a given point in time based on plaque, scaling and redness. A physician can rate a patient’s psoriasis as clear (0), almost clear (1), mild (2), moderate (3), severe (4), or very severe (5).