November 12, 2014
By Riley McDermid, BioSpace.com Breaking News Editor
Amgen and British drugmaker AstraZeneca said today that their Phase III trial of psoriasis drug brodalumab met its primary endpoints when compared with both Stelara (ustekinumab) and a placebo at week 12 when tested on more than 1,800 patients with moderate-to-severe plaque psoriasis.
The AMAGINE-3 study, a pivotal, multi-arm Phase 3 trial, also found 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). 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 greater proportion of patients also achieved clear or almost clear skin at week 12 compared with placebo, according to the static Physician Global Assessment (sPGA 0 or 1).
Total clearance of the skin in the treatment of psoriasis is rare and could give many patients enormous hope if a proven therapy is found, said the companies.
“Despite a variety of treatment options available for psoriasis, many patients still do not meet skin clearance goals,” said Sean Harper, 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.”
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, which prevents the body from receiving signals that may lead to inflammation. Brodalumab is also currently being investigated for the treatment of psoriatic arthritis (Phase 3) and asthma (Phase 2).
The two companies said that results showed that 36.7 percent of patients in the brodalumab 210 mg group, 27 percent of patients in the brodalumab 140 mg group, 18.5 percent of patients in the Stelara group and 0.3 percent of patients in the placebo group achieved total clearance of skin disease (PASI 100). In addition, 85.1 percent of patients in the brodalumab 210 mg group, 69.2 percent of patients in the brodalumab 140 mg group, 69.3 percent of patients in the Stelara group and 6.0 percent of patients in the placebo group achieved PASI 75.
The most common adverse events that occurred in the brodalumab arms were common cold, joint pain, upper respiratory tract infection and headache.
