Study Evaluating Novel Investigational IL-17 Receptor Antibody Meets All Primary and Secondary Endpoints
THOUSAND OAKS, Calif. and LONDON, May 9, 2014 /PRNewswire/ -- Amgen (NASDAQ: AMGN) and AstraZeneca today 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."
AMAGINE-1 is one of three Phase 3 studies designed to assess the efficacy and safety of brodalumab in patients with moderate-to-severe plaque psoriasis. AMAGINE-2 and AMAGINE-3 are designed to evaluate the efficacy and safety of induction and maintenance regimens of brodalumab at different dose schedules in patients with moderate-to-severe plaque psoriasis compared to ustekinumab and placebo.
AMAGINE-1 Study Design
AMAGINE-1 assessed the safety and efficacy of brodalumab given every two weeks via subcutaneous injection at two doses (140 mg or 210 mg) compared to placebo in patients with moderate-to-severe plaque psoriasis. Another purpose of the study was to assess safety and efficacy when patients treated with brodalumab, who responded to treatment, began receiving placebo compared to the patients who continued receiving brodalumab.
The Phase 3 study began with a 12-week, double-blind, placebo-controlled induction phase. During this phase, patients were randomized in a 1:1:1 ratio to receive 210 mg of brodalumab, 140 mg of brodalumab or placebo every two weeks.
At week 12, patients originally randomized to receive treatment with brodalumab who achieved clear or almost clear skin according to their sPGA (0 or 1) were rerandomized 1:1 to receive placebo or continued treatment with brodalumab at the current dose. Rerandomized patients losing disease control were treated with their original brodalumab dose. All patients originally randomized to placebo and any patient not qualifying for rerandomization (sPGA > 1) received 210 mg of brodalumab every two weeks.
sPGA is a physician's rating of psoriasis severity at a given point in time based on plaque, scaling and redness. A physician can rate a patient's psoriasis as clear (0), almost clear (1), mild (2), moderate (3), severe (4) or very severe (5).
About Brodalumab (AMG 827)
Brodalumab is a novel 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. By stopping IL-17 ligands from activating the receptor, brodalumab prevents the body from receiving signals that may lead to inflammation. The IL-17 pathway plays a central role in inducing and promoting inflammatory disease processes. In addition to moderate-to-severe plaque psoriasis (Phase 3), brodalumab is currently being investigated for the treatment of psoriatic arthritis (Phase 3) and asthma (Phase 2).
About the Amgen and AstraZeneca Collaboration
In April 2012, Amgen and AstraZeneca formed a collaboration to jointly develop and commercialize five monoclonal antibodies from Amgen's clinical inflammation portfolio. With oversight from joint governing bodies, Amgen leads clinical development and commercialization for brodalumab (Phase 3 for moderate-to-severe plaque psoriasis and psoriatic arthritis, Phase 2 for asthma) and AMG 557/MEDI5872 (Phase 1b for autoimmune diseases such as systemic lupus erythematosus). AstraZeneca, through its biologics arm MedImmune, leads clinical development and commercialization for MEDI7183/AMG 181 (Phase 2 for ulcerative colitis and Crohn's disease), MEDI2070/AMG 139 (Phase 2 for Crohn's disease) and MEDI9929/AMG 157 (Phase 2 for asthma).
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology.
Amgen focuses on areas of high unmet medical need and leverages its biologics manufacturing expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be the world's largest independent biotechnology company, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential.
AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases. AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. For more information please visit: www.astrazeneca.com.
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