June 02, 2021: “A new post-hoc analysis of pooled data from the TULIP Phase III clinical trials being presented at the annual European Congress of Rheumatology (EULAR 2021) showed anifrolumab was consistently associated with improvements in both skin rash and arthritis across three different disease measures each, compared to placebo, in patients with moderate to severe systemic lupus erythematosus (SLE).
The analysis examined disease manifestations in the two most commonly impacted organ domains in SLE.
Anifrolumab is a potential first-in-class type I interferon inhibitor.
For skin rash, the difference in response rates for anifrolumab versus placebo at week 52 were 13.5% SLE Disease Activity Index (SLEDAI), 15.5% British Isles Lupus Assessment Group index (BILAG) and 15.6% modified Cutaneous Lupus Erythematosus Disease Area and Severity Index (mCLASI).
For arthritis, differences in response rates were 8.2% SLEDAI, 11.8% BILAG and 12.6% joint response.
Joan Merrill, Oklahoma Medical Research Foundation, Arthritis & Clinical Immunology Research Program, US, said: “Arthritis and rash are the most common and persistent problems in lupus and often have a significant impact on a person’s life.
The strength of the data from this analysis is that anifrolumab was found to be consistently effective using three different ways of looking at rash and three different approaches to arthritis.
Capturing multiple aspects of improvement increases confidence that anifrolumab may be an important option for patients.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “The data being presented at EULAR add to the growing body of evidence for anifrolumab that demonstrate a compelling clinical profile with the potential to address significant unmet medical needs in this debilitating disease.
With no new systemic lupus erythematosus treatments in over a decade, we’re working to make this new medicine available as soon as possible.”
The most frequently reported adverse events for anifrolumab in the TULIP-1 and TULIP-2 trials were upper respiratory tract infection, bronchitis, infusion-related reactions and herpes zoster.
AstraZeneca’s application for anifrolumab in SLE is under review by regulatory authorities in the US, EU and Japan, with decisions anticipated in the second half of 2021. Anifrolumab is not currently approved in any country.
Systemic lupus erythematosus
Systemic lupus erythematosus is an autoimmune disease in which the immune system attacks healthy tissue in the body.
It is a chronic and complex disease with a variety of clinical manifestations that can impact many organs and can cause a range of symptoms including pain, rashes, fatigue, swelling in joints and fevers.
More than 50% of patients with SLE develop permanent organ damage, caused by the disease or existing treatments, which exacerbates symptoms and increases the risk of mortality.
At least five million people worldwide have a form of lupus.
No new treatments have been approved for SLE in over 10 years.
TULIP-1, TULIP-2 in SLE
The pivotal TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) Phase III programme includes two trials, TULIP-1 and TULIP-2, that evaluated the efficacy and safety of anifrolumab versus placebo.
Both were randomised, double-blinded, placebo-controlled trials in patients with moderate to severe autoantibody-positive SLE who were receiving standard therapy.
Standard therapy consisted of oral corticosteroids (OCS), antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil, known as MMF).
TULIP-2 demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard therapy.
In the trial, 362 eligible patients were randomised (1:1) and received a fixed-dose intravenous infusion of 300mg anifrolumab or placebo every four weeks.
TULIP-2 assessed the effect of anifrolumab in reducing disease activity as measured by the BILAG-Based Composite Lupus Assessment (BICLA) scale.
In TULIP-1, 457 eligible patients were randomised (1:2:2) and received a fixed-dose intravenous infusion of 150mg anifrolumab, 300mg anifrolumab or placebo every four weeks, in addition to standard therapy.
The trial did not meet its primary endpoint based on the SLE Responder Index 4 (SRI4) composite measure.
In SLE, along with the pivotal TULIP Phase III programme, anifrolumab continues to be evaluated in a long-term extension Phase III trial.
A Phase II trial of anifrolumab in SLE using subcutaneous delivery has been completed.
In addition, AstraZeneca is exploring the potential of anifrolumab in a variety of diseases where type I interferon plays a key role, including lupus nephritis, cutaneous lupus erythematosus and myositis.
The analysis presented at EULAR included three different disease measures per organ domain.
Anifrolumab is a fully human monoclonal antibody that binds to subunit 1 of the type I interferon receptor, blocking the activity of type I interferons.
Type I interferons such as IFN-alpha, IFN-beta and IFN-kappa are cytokines involved in regulating the inflammatory pathways implicated in lupus.
The majority of adults with lupus have increased type I interferon signalling, which is known to be associated with disease activity and severity.
AstraZeneca acquired global rights to anifrolumab through an exclusive license and collaboration agreement with Medarex, Inc. in 2004.
Medarex was acquired by Bristol-Myers Squibb in 2009.
AstraZeneca in Respiratory & Immunology
Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s three therapy areas and is a key growth driver for the Company.
AstraZeneca is an established leader in respiratory care with a 50-year heritage.
The Company aims to transform the treatment of asthma and COPD by focusing on earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death.
The Company’s early respiratory research is focused on emerging science involving immune mechanisms, lung damage and abnormal cell-repair processes in disease and neuronal dysfunction.
With common pathways and underlying disease drivers across respiratory and immunology, AstraZeneca is following the science from chronic lung diseases to immunology-driven disease areas.
The Company’s growing presence in immunology is focused on five mid- to late-stage franchises with multi-disease potential, in areas including rheumatology (including systemic lupus erythematosus), dermatology, gastroenterology, and systemic eosinophilic-driven diseases.
AstraZeneca’s ambition in Respiratory & Immunology is to achieve disease modification and durable remission for millions of patients worldwide.”