Amgen And AstraZeneca Announce Positive Results From Second Pivotal Phase 3 Study Of Brodalumab In Patients With Moderate-To-Severe Plaque Psoriasis

Amgen(NASDAQ: AMGN) and AstraZeneca (NYSE: AZN) today announced thatAMAGINE-3(TM) , a pivotal, multi-arm Phase 3 trial evaluating two doses ofbrodalumab in more than 1,800 patients with moderate-to-severe plaquepsoriasis, met its primary endpoints when compared with both Stelara(R)(ustekinumab) and placebo at week 12. Brodalumab was shown to be superior toStelara on the primary endpoint of achieving total clearance of skindisease, as measured by the Psoriasis Area Severity Index (PASI 100). Whencompared with placebo, a significantly greater proportion of patientstreated with brodalumab achieved at least a 75 percent improvement frombaseline in disease severity at week 12, as measured by the Psoriasis AreaSeverity Index (PASI 75). A significantly greater proportion of patientstreated with brodalumab also achieved clear or almost clear skin at week 12compared with placebo, according to the static Physician Global Assessment(sPGA 0 or 1). All key secondary endpoints comparing brodalumab with Stelaraand placebo were also met. Results showed that 36.7 percent of patients in the brodalumab 210 mg group,27.0 percent of patients in the brodalumab 140 mg group, 18.5 percent ofpatients in the Stelara group and 0.3 percent of patients in the placebogroup achieved total clearance of skin disease (PASI 100). In addition,85.1 percent of patients in the brodalumab 210 mg group, 69.2 percent ofpatients in the brodalumab 140 mg group, 69.3 percent of patients in theStelara group and 6.0 percent of patients in the placebo group achieved PASI75. "Despite a variety of treatment options available for psoriasis, manypatients still do not meet skin clearance goals," said Sean E. Harper, M.D.,executive vice president of Research and Development at Amgen. "Theseresults are of particular importance as they are the first to demonstratesuperiority to Stelara in achieving total skin clearance, and the secondpositive pivotal Phase 3 study evaluating brodalumab in patients withmoderate-to-severe plaque psoriasis." The most common adverse events that occurred in the brodalumab arms (morethan 5 percent of patients in either group) were common cold, joint pain,upper respiratory tract infection and headache. Serious adverse eventsoccurred in 1.4 percent of patients in the 210 mg group and 1.6 percent ofpatients in the 140 mg group compared with 0.6 percent for Stelara and 1.0percent for placebo during the placebo-controlled period. Brodalumab is the only investigational treatment in development that bindsto the interleukin-17 (IL-17) receptor and inhibits inflammatory signalingby blocking the binding of several IL-17 cytokines (A, F, A/F and C) to thereceptor. The IL-17 receptor and cytokine family play a central role indevelopment and clinical manifestation of plaque psoriasis. "These results add to the growing body of evidence supporting the potentialvalue that brodalumab may bring to the treatment of psoriasis by targetingthe IL-17 receptor," said Briggs W. Morrison, M.D., executive vice presidentof Global Medicines Development at AstraZeneca. "We look forward to sharingresults later this year from AMAGINE-2(TM) , our remaining head-to-headstudy evaluating brodalumab versus Stelara." The AMAGINE program is composed of three Phase 3 studies designed to assessthe efficacy and safety of brodalumab in patients with moderate-to-severeplaque psoriasis. Top-line results from AMAGINE-1(TM) , designed to assessthe efficacy and safety of brodalumab compared with placebo, were releasedin May 2014. Detailed results from the AMAGINE-3 study will be submitted tothe 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 ofbrodalumab given at two doses every two weeks via subcutaneous injectioncompared with placebo and Stelara in patients with moderate-to-severe plaquepsoriasis. The study also assessed the safety and efficacy of fourmaintenance regimens of brodalumab. The primary endpoint comparingbrodalumab with Stelara was the proportion of patients achieving totalclearance of skin disease, as measured by PASI 100 at week 12. Whencomparing brodalumab with placebo, the primary endpoints included theproportion of patients achieving at least a 75 percent improvement frombaseline in disease severity (PASI 75) at week 12, and the achievement ofclear 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- andplacebo-controlled induction phase, where patients were randomized in a2:2:1:1 ratio to receive brodalumab (210 mg or 140 mg), Stelara (per thelabeled dose), or placebo. At week 12, patients originally randomized toeither brodalumab arm were re-randomized 2:2:2:1 into the maintenance phaseto receive brodalumab 210 mg or 140 mg at four different maintenanceregimens. Patients originally randomized to Stelara continued to receive thesame treatment, and those originally randomized to receive placebo began 210mg of brodalumab every two weeks. At week 52, patients entered the long-term extension portion of the study,and those who were originally randomized to receive Stelara began receiving210 mg of brodalumab every two weeks. All other patients continued ontreatment with brodalumab at the same dose they were being treated with atweek 52. Patients may be enrolled in the study for up to 271 weeks(approximately five years). A PASI score is a measure of psoriatic plaque redness, scaling and thicknessand the extent of involvement in each region of the body. Treatment efficacyis often measured by the reduction of PASI from baseline (e.g., a 75 percentreduction is known as PASI 75, a 90 percent reduction is known as PASI 90and PASI 100 is total clearance of skin disease). sPGA is a physician's rating of psoriasis severity at a given point in timebased on plaque, scaling and redness. A physician can rate a patient'spsoriasis as clear (0), almost clear (1), mild (2), moderate (3), severe(4), or very severe (5).