Amgen and AstraZeneca yesterday reported positive results for brodalumab, saying it met its primary endpoints in a Phase III trial that compared the human anti-IL-17 receptor A monoclonal antibody with both Stelara® (ustekinumab) and placebo after 12 weeks in patients with moderate-to-severe plaque psoriasis.
More than 1,800 such patients were evaluated for two doses of brodalumab in the Phase III AMAGINE-2TM study. Patients taking brodalumab 210 mg every two weeks and the brodalumab weight-based analysis group each showed superiority to Stelara on the primary endpoint of achieving total clearance of skin disease, as measured by the Psoriasis Area Severity Index (PASI 100), the companies said.
Results showed that 44.4% of patients in the brodalumab 210 mg group achieved total clearance of skin disease (PASI 100), compared with 33.6% of patients in the brodalumab weight-based group, 25.7% in the brodalumab 140 mg group, 21.7% in the Stelara group, and 0.6% in the placebo group.
Also, 86.3% of patients in the brodalumab 210 mg group, achieved clear or almost clear skin at week 12 compared with placebo, according to the static Physician Global Assessment (sPGA 0 or 1). Percentages for the other patient groups were 77.0% for the brodalumab weight-based group, 66.6% for the brodalumab 140 mg group, 70.0% for the Stelara group, and 8.1% for the placebo group.
According to Amgen and AstraZeneca, 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, as were the remaining secondary endpoints against Stelara, but likewise could not be deemed statistically significant.
“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,” Sean E. Harper, M.D., Amgen’s evp of research and development, said in a statement.
Added Briggs W. Morrison, M.D., AstraZeneca’s evp of global medicines development: “These results confirm our belief that targeting the IL-17 receptor to inhibit inflammatory signaling can have significant benefit for psoriasis patients. We look forward to sharing detailed results from the AMAGINE program in upcoming scientific forums.”
The companies said they planned to submit regulatory filings for marketing approvals of brodalumab in 2015.
AMAGINE-2 is the third and final pivotal study in the company’s Phase III psoriasis program. Earlier this month, Amgen and AstraZeneca trumpeted upbeat top-line results from AMAGINE-3TM, which was identical to AMAGINE-2 in comparing brodalumab with Stelara and placebo. The companies released positive top-line results from AMAGINE-1TM, comparing brodalumab with placebo, were released in May.
In addition to moderate-to-severe plaque psoriasis, brodalumab is currently being investigated for the treatment of psoriatic arthritis (Phase III) and asthma (Phase II).
“The robust data from these studies will form the basis of our global filing plan. We look forward to discussions with regulatory authorities,” Dr. Harper added.
Brodalumab, once called AMG 827, is one of five monoclonal antibodies from Amgen's clinical inflammation portfolio that the biotech giant is jointly developing and commercializing with AstraZeneca under an April 2012 collaboration agreement.
AstraZeneca agreed to pay Amgen a $50 million upfront payment, with the companies agreeing to share both costs and profits—with an estimated 65% of costs for the 2012–2014 period funded by AstraZeneca, and the companies agreeing to equally split the costs afterward.
The collaboration agreement also allowed Amgen to book sales globally, while retaining a “low single-digit” royalty for brodalumab, as well as a “mid single-digit” royalty for the rest of the portfolio, after which the companies agreed to share profits equally.
Under that accord, Amgen agreed to lead development of brodalumab as well as AMG557/MEDI5872, a compound now under Phase Ib study for autoimmune diseases such as systemic lupus erythematosus, with AstraZeneca, through its biologics arm MedImmune, leading development of MEDI7183/AMG 181 (Phase II for ulcerative colitis and Crohn's disease), MEDI2070/AMG 139 (Phase II for Crohn's disease) and MEDI9929/AMG 157 (Phase II for asthma).