Tuesday, 11 November 2014
AstraZeneca, with its global biologics research and development arm, MedImmune, will present new data from the company’s growing inflammation and autoimmunity portfolio at the American College of Rheumatology (ACR) 2014 Annual Meeting in Boston, Massachusetts, 14-19 November 2014.
More than 15 abstracts will be featured at the ACR meeting, providing evidence of the depth and continued progress of AstraZeneca’s inflammation and autoimmunity pipeline. Positive Phase III data will be presented on lesinurad in gout, as well as earlier stage data around a number of innovative investigational medicines including sifalimumab and anifrolumab in systemic lupus erythematosus (SLE, or lupus), mavrilimumab in rheumatoid arthritis, and brodalumab in psoriatic arthritis.
Briggs Morrison, Executive Vice President, Global Medicines Development and Chief Medical Officer, AstraZeneca, said: “The breadth of research we will present at ACR reinforces our commitment to delivering medicines that could help to improve the lives of millions of patients suffering from inflammation and autoimmune diseases. This is an excellent demonstration of our pipeline delivering promising molecules with the potential to address difficult to treat diseases including gout, lupus, rheumatoid arthritis and psoriatic arthritis.
Bahija Jallal, Executive Vice President, MedImmune said: “We are pioneering innovative research and exploring new pathways in both lupus and rheumatoid arthritis. We continue to push scientific boundaries, advancing our understanding of the drivers and mechanisms of these diseases for the benefit of patients.”
Highlights of data being presented include:
• Lesinurad: Positive top-line results from CLEAR1 and CLEAR2, the pivotal Phase III clinical trials investigating the potential of lesinurad, a selective uric acid re-absorption inhibitor (SURI), as a combination therapy with xanthine oxidase (XO) inhibitor, allopurinol for the treatment of patients with symptomatic gout. The development of lesinurad is potentially important for the 40-70% of gout patients who are not reaching target levels of serum uric acid (sUA) with the current standard of care.
• Sifalimumab and anifrolumab: MedImmune is currently investigating two different anti-type 1 interferon (IFN) approaches in the clinic as potential treatments for lupus: sifalimumab, which targets IFN-α, and anifrolumab, which targets the type 1 IFN receptor. Positive results from the Phase IIb study evaluating the safety and efficacy of sifalimumab in patients with moderate-to-severe lupus will be presented in a late-breaking oral presentation. In addition, pharmacokinetic and pharmacodynamic data will be presented on both sifalimumab and anifrolumab from two trials of adult Japanese patients with lupus.
• Mavrilimumab: Positive results from the Phase IIb EARTH EXPLORER I study evaluating the efficacy and safety of mavrilimumab in patients with moderate-to-severe adult-onset rheumatoid arthritis will be presented in four abstracts, including an oral presentation. Mavrilimumab, currently in development by MedImmune, is a novel human monoclonal antibody targeting the GM-CSF receptor, a key pathway driving the rheumatoid arthritis disease process.
• Brodalumab: Data will be presented from an open-label extension of a Phase II study on the long-term efficacy and safety of brodalumab, a human anti-IL-17 receptor A monoclonal antibody for patients with psoriatic arthritis. Additionally, an analysis to evaluate the reliability and construct validity of the Psoriasis Symptom Inventory in subjects with psoriatic arthritis will also be presented. Brodalumab is being co-developed by Amgen and AstraZeneca.
Key AstraZeneca abstracts to be featured at ACR:
Gout (lesinurad) Abstracts
• #105 Morlock R, et al. Resource Use and Health Related Quality of Life Burden of Gout Exacerbated By Common Comorbidities: Results from the 2012-2013 National Health and Wellness Survey. General poster session, 8:30 AM – 4:00 PM ET Sunday, 16 November 2014.
• #180 Paraskos J, et al. Analytical Comparison Between Point of Care Uric Acid Testing Meters. General poster session 8:30 AM – 4:00 PM ET Sunday, 16 November 2014.
• #901 Morlock R, et al. Rate of Serum Uric Acid (SUA) Assessment in Gout Patients Treated with Urate-Lowering Therapy: Treating to Target? Oral presentation, 4:30 PM – 6:00 PM ET Sunday,16 November 2014.
• #1165 Morlock R, et al. Evaluation of Symptom Control Among Treated Gout Patients in the United States, United Kingdom, and Germany. General poster session 8:30 AM – 4:00 PM ET Monday, 17 November 2014.
• #L10 Saag, K, et al. Lesinurad, a Novel Selective Uric Acid Reabsorption Inhibitor, in Two Phase III Clinical Trials: Combination Study of Lesinurad in Allopurinol Standard of Care Inadequate Responders (CLEAR 1 and 2). ACR late-breaking abstract poster display, 9:00 AM – 11:00 AM ET Sunday, 16 November - Tuesday, 18 November. ACR late-breaking abstract poster presentations, 9:00 AM – 11:00 AM ET Tuesday, 18 November 2014.
• #2963 Tan P, et al. The URAT1 Uric Acid Transporter Is Important in Uric Acid Homeostasis and Its Activity May be Altered in Gout Patients and in Drug-Induced Hyperuricaemia. Oral presentation, 9:00 AM – 10:30 AM ET Wednesday, 19 November 2014.
Lupus (sifalimumab and anifrolumab) Abstracts
• #719 Morehouse C, et al. Target Modulation of a Type I Interferon (IFN) Gene Signature with Sifalimumab or Anifrolumab in Systemic Lupus Erythematosus (SLE) Patients in Two Open Label Phase 2 Japanese Trials. General poster session, 8:30 AM–4:00 PM ET, Sunday, 16 November 2014.
• #1619 Drubin D, et al. Interferon Dysregulation in an Academic SLE Cohort Is Associated with Distinct Signaling Differences in Blood Neutrophils Versus PBMCs. General poster session 8:30 AM – 4:00 PM ET Monday, 17 November 2014.
• # L4 Khamashta, M et al. Safety and Efficacy of Sifalimumab, an Anti IFN-Alpha Monoclonal Antibody, in a Phase 2b Study of Moderate to Severe Systemic Lupus Erythematosus (SLE). Late-breaking abstracts session, 3:15 PM ‒ 3:30 PM ET, Tuesday, 18 November 2014.
Rheumatoid Arthritis (mavrilimumab) Abstracts
• #1143 Kern D, et al. Preferences of Biologic Treatment Characteristics Among Rheumatoid Arthritis Patients Who Are Current Biologic Therapy Users. General poster session, 8:30 AM– 4:00 PM ET, Monday, 17 November, 2014.
• #1485 Kremer J, et al. Analysis of Patient-Reported Outcomes during Treatment with Mavrilimumab, a Human Monoclonal Antibody Targeting GM-CSFRα, in the Randomized Phase 2b Earth Explorer 1 Study. General poster session 8:30 AM–4:00 PM ET Monday, 17 November, 2014.
• #1486 McInnes I, et al. Rapid Onset of Clinical Benefit Is Associated with a Reduction in Validated Biomarkers of Disease in Patients with Rheumatoid Arthritis Treated with Mavrilimumab, a Human Monoclonal Antibody Targeting GM-CSFRα. General poster session, 8:30 AM – 4:00 PM ET Monday, 17 November 2014.
• #1496 Wu C, et al. Exposure-Response Analysis for Mavrilimumab Phase IIb Study in RA Patients with Informative Dropout. General poster session, 8:30 AM – 4:00 PM ET Monday, 17 November 2014.
• #2821 Burmester G, et al. Efficacy and Safety/Tolerability of Mavrilimumab, a Human GM‒CSFRα Monoclonal Antibody in Patients with Rheumatoid Arthritis. Oral presentation, 2:30PM – 4:00 PM ET Tuesday, 18 November 2014.
Psoriatic Arthritis (brodalumab) Abstracts
• #549 Mease P, et al. Reliability and Construct Validity of the Psoriasis Symptom Inventory in Subjects with Psoriatic Arthritis. General poster session 8:30 AM – 4:00 PM ET Sunday, 16 November 2014.
• #1557 Genovese M, et al. Clinical Response in Subjects with Psoriatic Arthritis Following One Year of Treatment with Brodalumab, an Anti-Interleukin-17 Receptor Antibody. General poster session 8:30 AM – 4:00 PM ET Monday, 17 November 2014.
NOTES FOR EDITORS
Gout is a serious condition marked by chronic and debilitating inflammatory arthritis. There were 15.3 million diagnosed cases of chronic gout in major markets in 2013, and this is forecast to grow to 17.7 million by 2021. Gout is caused by a metabolic disorder, hyperuricaemia (elevated levels of serum acid, sUA), which leads to the deposition of crystals in musculoskeletal structures including joints, the kidneys and other tissues.
The goal of all urate lowering treatments is to reduce sUA concentrations to the recommended targets. International treatment guidelines from the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) recommend achieving an sUA target at a minimum of <6.0 mg/dL in all gout patients and often to <5.0 mg/dL in gout patients with greater disease severity and urate burden, such as those with tophi (visible deposits of monosodium serum urate crystals, which can appear around the joints and in other tissues).
About Systemic Lupus Erythematosus
Lupus is an autoimmune disease in which the immune system produces antibodies that, instead of targeting viruses or other foreign invaders, attack healthy tissue in the body, including skin, joints, the brain and blood vessels. SLE can cause a range of symptoms, including pain, rashes, fatigue, swelling in joints, and fevers. It is associated with a greater risk of death from causes such as infection and cardiovascular disease.
About Rheumatoid Arthritis
Rheumatoid arthritis is a painful, systemic, chronic inflammatory autoimmune disease that causes damage to the joints and vital organs. The disease affects approximately one in 100 people worldwide. If not adequately treated, RA is a major cause of disability leading to diminished work capacity and is associated with reduced life expectancy.
About Psoriatic Arthritis
Psoriatic arthritis is a chronic disease of the immune system that causes joint pain, stiffness, and swelling that can become progressively worse over time. It may also include red patches of skin topped with silvery scales. The progressive, irreversible joint damage, pain and swelling, coupled with painful, scaly and red skin patches, can disrupt a patient’s ability to perform daily activities, such as using their hands, standing for long periods or walking. PsA affects 30 to 50 percent of approximately 125 million people worldwide who have psoriasis.
Lesinurad is an investigational agent for gout being studied as a selective uric acid reabsorption inhibitor (SURI) that inhibits the URAT1 transporter. URAT1 is responsible for the majority of the reabsorption of filtered uric acid from the renal tubular lumen. By inhibiting URAT1, lesinurad increases uric acid excretion and thereby lowers sUA. Lesinurad also inhibits OAT4, a uric acid transporter involved in diuretic-induced hyperuricaemia. Lesinurad is being developed as an oral, once-daily combination treatment for chronic gout.
About Sifalimumab and Anifrolumab
Sifalimumab (formerly MEDI-545) is an investigational human monoclonal antibody that targets IFN-α, a type of inflammatory cytokine in the body known to play a role in the development of SLE. Previous studies have shown that elevated levels of type I IFN-α are correlated with more severe disease activity in SLE patients and early studies of sifalimumab have demonstrated that this agent inhibits signaling of interferon alpha subtypes.
Anifrolumab (formerly MEDI-546) is an investigational human monoclonal antibody that binds to subunit 1 of the Type I IFN receptor, inhibiting the activity of all Type I IFNs including IFN-IFN- and IFN-. Anifrolumab is the only anti-Type I IFN receptor approach currently in development for SLE. It is being studied in an ongoing Phase IIb clinical study in patients with moderate to severe SLE, with full results anticipated to be presented in 2015.
Mavrilimumab (formerly CAM-3001) is a first-in-class, fully human monoclonal antibody that targets the alpha receptor for the cytokine granulocyte-macrophage colony-stimulating factor (GM‒CSF). Through the targeted blockade of the GM-CSF receptor on the macrophage, a key cell in the pathogenesis of rheumatoid arthritis, mavrilimumab could add a significant new treatment option for RA patients.
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 psoriatic arthritis (Phase III), brodalumab is currently being investigated for the treatment of moderate to severe plaque psoriasis (Phase III) and asthma (Phase II).
About the Amgen and AstraZeneca Collaboration
In April 2012, Amgen and AstraZeneca formed a collaboration to jointly develop and commercialise five monoclonal antibodies from Amgen’s clinical inflammation portfolio. With oversight from joint governing bodies, Amgen leads clinical development and commercialisation for brodalumab (Phase III for moderate-to-severe plaque psoriasis and psoriatic arthritis, Phase II for asthma) and AMG 557/MEDI5872 (Phase Ib for autoimmune diseases such as systemic lupus erythematosus). AstraZeneca, through its biologics arm MedImmune, leads clinical development and commercialisation for 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).
MedImmune is the global biologics research and develoment arm of AstraZeneca. MedImmune is pioneering innovative research and exploring novel pathways across key therapeutic areas, including respiratory, inflammation and autoimmunity; cardiovascular and metabolic disease; oncology; neuroscience; and infection and vaccines. The MedImmune headquarters is located in Gaithersburg, Md., one of AstraZeneca’s three global R&D centers. For more information, please visit www.medimmune.com.
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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