Date: 2014-06-11
Type of information: Publication of results in a medical journal
phase: 2
Announcement: publication of results in the New England Journal of Medicine
Company: Amgen (USA) AstraZeneca (UK)
Product: brodalumab (AMG 827)
Action
mechanism: Brodalumab is a highly-selective human monoclonal antibody that binds to and blocks signaling via the interleukin-17 (IL-17) receptor. The IL-17 pathway plays an important role in inducing and promoting inflammatory disease processes. Blocking inflammatory signaling at the IL-17 receptor may be beneficial in the treatment of moderate to severe plaque psoriasis, psoriatic arthritis, and potentially other immune-mediated diseases.
In April 2012, Amgen and AstraZeneca have announced an agreement to jointly develop and commercialize five monoclonal antibodies from Amgen\'s clinical inflammation portfolio (AMG 139, AMG 157, AMG 181, AMG 557 and brodalumab - AMG 827). 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).
Disease: psoriatic arthritis
Therapeutic area: Autoimmune diseases
Country:
Trial
details: The study was a Phase 2, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of brodalumab in psoriatic arthritis. Patients with active psoriatic arthritis were randomized to receive brodalumab (140 or 280 mg subcutaneously) or placebo at day 1 and weeks 1, 2, 4, 6, 8, and 10. At week 12, patients were offered open-label brodalumab 280 mg every two weeks.
Active psoriatic arthritis was defined by the Classification of Psoriatic Arthritis criteria (CASPAR)2 with >3 tender and >3 swollen joints.
Latest
news: * On June 11, 2014, Amgen and AstraZeneca announced that results from a Phase 2 study evaluating brodalumab in 168 patients with psoriatic arthritis were published in The New England Journal of Medicine (NEJM). These data will also be presented at the 2014 European League Against Rheumatism (EULAR) Annual Congress in Paris on June 14, 2014. 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. The IL-17 pathway plays a central role in inducing and promoting inflammatory disease processes. The study showed that treatment with brodalumab significantly improved signs and clinical symptoms associated with the disease, including tender and swollen joints, at 12 weeks as measured by a 20 percent improvement in the American College of Rheumatology response criteria (ACR20). The study also showed that many patients continued to improve, and that the improvements were sustained, through the first 52 weeks of the study reported in NEJM. The study achieved its primary endpoint with both doses of brodalumab exhibiting superiority to placebo in ACR20 responses at week 12. These responses continued to improve through 24 weeks and were sustained through the first 52 weeks of the study.1 ACR response criteria are a measure of improvement in tender and swollen joints, as well as patient and physician global assessments of disease activity, pain, disability and inflammatory markers. A 20 percent improvement from baseline in ACR response rates is known as ACR20, a 50 percent improvement from baseline is known as ACR50 and a 70 percent improvement from baseline is known as ACR70.Overall, adverse events were similar across groups with 3 percent of brodalumab-treated patients experiencing serious adverse events versus 2 percent of placebo recipients (four patients in total). Serious adverse events included skin infection (cellulitis, two cases), abdominal pain and inflammation of the gallbladder (cholecystitis). No clinically significant neutropenia (>Grade 2) was reported in this study. At 12 weeks, 37 percent of patients treated with 140 mg of brodalumab (n=21/57) and 39 percent of patients treated with 280 mg of brodalumab (n=22/56) achieved an ACR20 response compared to 18 percent of patients treated with placebo (n=10/55) (p=0.03 and p=0.02, respectively). After 12 weeks of treatment, all patients began receiving 280 mg of brodalumab every two weeks in an unblinded fashion. Improvements observed among brodalumab-treated patients in the first 12 weeks continued. At 24 weeks, 51 percent of patients treated in the first 12 weeks with 140 mg of brodalumab (n=24/47) and 64 percent of patients treated in the first 12 weeks with 280 mg of brodalumab (n=29/45) achieved ACR20 responses, compared to 44 percent of patients who switched from placebo to 280 mg of brodalumab at week 12 (n=20/46). Responses were sustained through 52 weeks. At 12 weeks, 14 percent of patients in both groups treated with brodalumab [140 mg dose (n=8/57) and 280 mg dose (n=8/56)] achieved ACR50 responses compared to 4 percent of patients treated with placebo (n=2/55) (p=0.05 for 280 mg dose vs placebo). ACR70 responses were not significantly higher in brodalumab groups than placebo groups. At 24 weeks, 33 percent of patients in both groups initially treated with brodalumab for the first 12 weeks [140 mg dose (n=16/49) and 280 mg dose (n=15/45)], followed by 280 mg of brodalumab from weeks 12 to 24, achieved ACR50 responses compared to 20 percent of patients initially treated with placebo (n=9/46). ACR50 and ACR70 response rates continued to improve through the remainder of the study. Safety endpoints included adverse events, which were overall similar across groups. Those most commonly reported in the combined brodalumab groups were upper respiratory tract infection (12 percent vs 7 percent for placebo), fatigue (7 percent vs 4 percent for placebo), diarrhea (6 percent vs 4 percent for placebo), and headache (6 percent vs 7 percent for placebo). Amgen and AstraZeneca have initiated two Phase 3 studies of brodalumab in psoriatic arthritis, AMVISION-1 and AMVISION-2, which together will provide detailed information on the impact of brodalumab on improving clinical signs and symptoms in psoriatic arthritis, as well as its ability to prevent joint damage.
