AstraZeneca and Amgen today announced that AMAGINE-2™, a pivotal, multi-arm Phase III 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 210 mg given every two weeks and the brodalumab weight-based analysis group were each 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 percent 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).
Results showed that 44.4 percent of patients in the brodalumab 210 mg group, 33.6 percent of patients in the brodalumab weight-based group, 25.7 percent of patients in the brodalumab 140 mg group, 21.7 percent of patients in the Stelara group and 0.6 percent of patients in the placebo group achieved total clearance of skin disease (PASI 100). In addition, 86.3 percent of patients in the brodalumab 210 mg group, 77.0 percent of patients in the brodalumab weight-based group, 66.6 percent of patients in the brodalumab 140 mg group, 70.0 percent of patients in the Stelara group and 8.1 percent of patients in the placebo group achieved PASI 75.
“Results from AMAGINE-2 underscore that treatment with brodalumab could help a significant number of moderate-to-severe plaque psoriasis patients achieve total clearance of their skin disease, and the great majority achieve at least a 75 percent improvement in their disease,” said Sean E. Harper, Executive Vice President of Research and Development at Amgen. “AMAGINE-2 is the third and final pivotal study in our Phase III psoriasis programme and the robust data from these studies will form the basis of our global filing plan. We look forward to discussions with regulatory authorities.”
All key secondary endpoints comparing brodalumab with placebo were met. The first key secondary endpoint comparing PASI 100 for brodalumab (140 mg) with Stelara at week 12 was numerically greater but not statistically significant (p=0.078). The remaining secondary endpoints against Stelara were also numerically greater (all nominal p-values were less than 0.05), but could not be deemed statistically significant due to the sequential testing method.
The most common adverse events that occurred in the brodalumab arms (more than 5 percent of patients in either group) were common cold, upper respiratory tract infection, headache and joint pain. Serious adverse events occurred in 1.0 percent of patients in the 210 mg group, 1.2 percent of patients in the weight-based group, and 2.1 percent of patients in the 140 mg group compared with 1.3 percent for Stelara and 2.6 percent for placebo during the placebo-controlled period. There was one (0.2 percent) fatal event of stroke in the brodalumab 210 mg group during the 12-week placebo-controlled induction phase, deemed by the study investigator as unrelated to treatment.
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 and A/F) to the receptor. The IL-17 receptor and cytokine family play a central role in development and clinical manifestations of plaque psoriasis.
“These results confirm our belief that targeting the IL-17 receptor to inhibit inflammatory signaling can have significant benefit for psoriasis patients,” said Briggs Morrison, Executive Vice President, Global Medicines Development and Chief Medical Officer, AstraZeneca. “We look forward to sharing detailed results from the AMAGINE programme in upcoming scientific forums.”
The AMAGINE programme is comprised of three pivotal Phase III studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. Top-line results from AMAGINE-1™, comparing brodalumab with placebo, were released in May 2014. Top-line results from AMAGINE-3™, comparing brodalumab with Stelara and placebo, were announced in November 2014. AMAGINE-2 and AMAGINE-3 are identical in design.
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