Amgen and AstraZeneca announced that the Phase 3 AMAGINE-1TM study evaluating brodalumab in patients with moderate-to-severe plaque psoriasis met all primary and secondary endpoints for both evaluated doses. 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 ligands to the receptor. Primary endpoints were patients achieving at least a 75 percent improvement from baseline in disease severity at week 12, as measured by the Psoriasis Area Severity Index (PASI 75), and patients achieving clear or almost clear skin at week 12 according to the static Physician Global Assessment (sPGA 0 or 1).
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 to placebo. Results showed that 83.3 percent of patients in the 210 mg group and 60.3 percent of patients in the 140 mg group achieved PASI 75 responses compared to placebo (2.7 percent). Results also showed that 70.3 percent of patients in the 210 mg group and 42.5 percent of patients in the 140 mg group achieved PASI 90 responses compared to placebo (0.9 percent). Further, 41.9 percent of patients in the 210 mg group and 23.3 percent of patients in the 140 mg group achieved PASI 100 responses compared to placebo (0.5 percent). Of the 661 patients enrolled in this study, 46 percent reported prior biologic use and 28.7 percent weighed more than 100 kilograms (kg) at baseline (mean weight for the study population was 90.8 kg).
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 (i.e., a 75 percent reduction is known as PASI 75, a 90 percent reduction is known as PASI 90 and PASI 100 is total clearance of skin disease).
The most common adverse events that occurred during the placebo-controlled period in the brodalumab group (more than 5 percent of participants) were nasopharyngitis, upper respiratory tract infection and headache. Serious adverse events occurred in 1.8 percent of patients in the 210 mg group and 2.7 percent of patients in the 140 mg group compared to 1.4 percent for placebo during the placebo-controlled period.
"Data from the AMAGINE-1 study suggest that brodalumab may offer a new level of efficacy for patients with moderate-to-severe plaque psoriasis, a disease that affects more than 100 million people globally," said Sean E. Harper, M.D., executive vice president of Research and Development at Amgen. "This is the first read-out from our Phase 3 psoriasis clinical program and we look forward to obtaining additional Phase 3 data from our two head-to-head studies versus ustekinumab later this year." Psoriasis is a non-contagious chronic disease in which the immune system causes skin cells to grow at an accelerated rate.Instead of being shed, skin cells pile up, causing painful and itchy, red, scaly patches.
"Moderate-to-severe plaque psoriasis is a serious disease, and despite available treatments, there is still a significant need for more effective therapies," said Briggs W. Morrison, M.D., executive vice president of Global Medicines Development at AstraZeneca. "We are encouraged by brodalumab's emerging profile and look forward to presenting the full data in the appropriate scientific forum."