AstraZeneca Announces Anifrolumab Meets Primary Endpoint in Phase III TULIP-2 Trial for Systemic Lupus Erythematosus

Today, AstraZeneca announced that anifrolumab, its investigational monoclonal antibody for the treatment of systemic lupus erythematosus (SLE), met the primary endpoint of significantly improving disease condition in the pivotal Phase 3 clinical trial TULIP-2. Anifrolumab is a monoclonal antibody that inhibits the type I interferon signaling pathway.

Systemic lupus erythematosus (SLE) is an autoimmune disease with an incidence rate of approximately 30 cases per 100,000 people in China. Approximately 90% of SLE patients are female. The main symptoms of SLE include fatigue, arthritis, myalgia, rash, alopecia, and fever; in severe cases, it can cause damage to vital organs such as the heart, lungs, and kidneys, posing a life-threatening risk. The pathogenesis of SLE is still under investigation and involves factors such as immune system dysregulation, genetic susceptibility, environmental triggers, and the activation of both innate and adaptive immune systems. Current guidelines recommend the use of antimalarial drugs, glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressants to control lupus activity and prevent organ damage. Over the past 60 years, only one new biologic agent, belimumab, has been approved for the treatment of lupus erythematosus.

Anifrolumab binds to subunit 1 of the type I interferon receptor, thereby antagonizing all activities associated with type I interferons (IFN-α, IFN-β, and IFN-ω). Type I interferons are a class of cytokines involved in inflammatory responses. IFN-α promotes the activation and differentiation of various immune cells, including driving the differentiation of autoreactive B lymphocytes into immunoglobulin-secreting plasma cells, promoting dendritic cell maturation, and inducing their expression of B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL). Between 60% and 80% of patients with systemic lupus erythematosus (SLE) exhibit a type I interferon high-expression signature, and type I interferon levels are positively correlated with the SLE Disease Activity Index (SLEDAI) score.

▲Mechanism of Action of Anifrolumab (Image source: Reference [3])

A total of 373 patients with moderate-to-severe systemic lupus erythematosus (SLE) participated in the TULIP-2 trial. They were randomized into two groups to receive either 300 mg of anifrolumab or placebo via intravenous injection every four weeks, in addition to standard therapy. The trial results demonstrated that anifrolumab significantly improved the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) index, yielding statistically significant and clinically meaningful disease remission. Improvement in BICLA indicates amelioration of disease activity across all organ systems without any new disease flares.

Dr. Mene Pangalos, Executive Vice President of Biopharmaceuticals R&D at AstraZeneca, said, “SLE is a debilitating autoimmune disease. Over the past 60 years, only one new therapy has been approved. The results from the TULIP trials are significant. We will review the complete dataset and are committed to bringing this potential new therapy to patients.”

References:

[1]. Anifrolumab Phase III trial meets primary endpoint in systemic lupus erythematosus. Retrieved Aug. 27, 2019, from https://www.astrazeneca.com/media-centre/press-releases/2019/anifrolumab-phase-iii-trial-meets-primary-endpoint-in-systemic-lupus-erythematosus-29082019.html

[2]. Dafna D Gladman. et al. （2017）Current and future therapies for SLE: obstacles and recommendations for the development of novel treatments. Lupus Science & Medicine. http://dx.doi.org/10.1136/lupus-2017-000239

[3]. Timothy B. Niewold. et al. （2016）Targeting type I interferon in systemic lupus erythematosus. Nature reviews rheumatology. https://www.nature.com/articles/nrrheum.2016.83

[4]. Express | First! FDA Approves First Therapy for Pediatric Lupus Erythematosus Today. Retrieved Aug. 27, 2019, from https://mp.weixin.qq.com/s/aQB01xMa7aLFesweOkrLsQ

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