Anifrolumab showed early and sustained treatment benefit for patients with systemic lupus erythematosus in the TULIP clinical trial programme

3 June 2020 13:45 BST
 

New pooled analyses presented at The EULAR E-Congress of Rheumatology 2020
 

AstraZeneca’s anifrolumab, a potential new medicine for the treatment of moderate to severe systemic lupus erythematosus (SLE), showed an early and sustained reduction of SLE disease activity, as measured by the British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) in a new pooled analysis of the Phase III TULIP 1 and TULIP 2 clinical trials.1

In an additional pooled analysis, anifrolumab showed consistent clinical benefits across all measured patient subgroups, including age, sex, age at onset and race, compared to placebo.2 Furthermore, anifrolumab also showed reduced annualised flare rates and prolonged time to first flare across both trials, compared to placebo, with both arms receiving standard of care.3

These data will be presented at The European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020 taking place virtually from 3-6 June 2020.

Professor Eric F. Morand, Monash University, Australia, said: “Systemic lupus erythematosus is a heterogenous disease and by demonstrating consistent benefit across patient subgroups these data show anifrolumab has the potential to be an important new option for patients. The early yet sustained effect seen in the trials could give clinicians an important indication that the treatment is managing their patient’s condition.”

Richard Marshall, Senior Vice President and Global Head of Respiratory and Immunology Late Stage Development, BioPharmaceuticals R&D, said: “These data further demonstrate the benefit of anifrolumab in treating moderate to severe systemic lupus erythematosus. With only one therapy approved for systemic lupus erythematosus in the last 60 years, we’re working to bring this potential treatment to patients living with this debilitating condition as quickly as possible.”
 

Results from the PHASE III TULIP programme include:

Study

Summary

Early and Sustained Responses with Anifrolumab Treatment in Patients with Active Systemic Lupus Erythematosus (SLE) in 2 Phase 3 Trials.1

 

Oral Abstract Presentation Session 03 June 2020 14:00 - 15:00
  • Greater percentages of patients treated with anifrolumab were classified as having showed a BICLA response compared with placebo at week 8 (35.0% vs 22.7%) and week 12 (39.9% vs 29.7%) in the pooled analysis.
  • Results favoured anifrolumab treatment with an earlier time to onset of BICLA response sustained through week 52 vs placebo. (Hazard ratio 1.73 (95% CI 1.37–2.20). 

Efficacy of Anifrolumab in Active Systemic Lupus Erythematosus: Patient Subgroup Analysis of BICLA Response in 2 Phase 3 Trials.2

Oral Abstract Presentation, 03 June 2020 16:00 - 17:30

 
  • Consistent BICLA response rates were observed at week 52 across prespecified subgroups in TULIP 1, TULIP 2, and pooled TULIP data, compared with placebo.
  • Uniformity of response was irrespective of baseline characteristics, including disease severity, baseline oral corticosteroid use, age, sex, age of disease onset, and race.

Flare Assessments in Patients with Active Systemic Lupus Erythematosus Treated with Anifrolumab in 2 Phase 3 Trials.3

Poster Presentation: 4 June 2020
  • Fewer patients treated with anifrolumab experienced a disease flare over 52 weeks in TULIP 1 (36.1% vs 43.5%) and TULIP 2 (31.1% vs 42.3%) compared with placebo.*
  • Reductions in annualised flare rates were seen in TULIP 1 (adjusted rate ratio [ARR] 0.83 [95% CI 0.61–1.15]) and TULIP 2 (ARR 0.67 [95% CI 0.48–0.94]).*
  • A prolonged time to first flare with anifrolumab treatment was seen in TULIP 1 (Hazard ratio [HR] 0.76 [95% CI 0.55–1.06]) and TULIP 2 (HR 0.65 [95% CI 0.46–0.91]) compared with placebo.*
  • Data from a pooled analysis will be made available in the poster.

 

* Flares were defined as ≥1 new BILAG-2004 A or ≥2 new (worsening) BILAG-2004 B domain scores compared with the prior month’s visit.
 

AstraZeneca is also presenting data from a real-world observational retrospective cohort study of 802 patients with SLE in the UK that further characterise the disease burden and costs associated with SLE.4,5

Systemic lupus erythematosus

SLE is an autoimmune disease in which the immune system attacks healthy tissue in the body.6 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.7 It is associated with a greater risk of death from causes such as infection and cardiovascular disease.8 There has been only one new medicine approved for SLE in the last 60 years.9

TULIP

The pivotal TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) programme includes two Phase III clinical trials, TULIP 1 and TULIP 2, that evaluated the efficacy and safety of anifrolumab versus placebo in patients with moderately to severely active autoantibody-positive SLE who are receiving standard of care treatment.

TULIP 1, which did not meet its primary endpoint in 2018, randomised 457 eligible patients (1:2:2) to receive a fixed-dose intravenous infusion of 150mg anifrolumab, 300mg anifrolumab, or placebo every four weeks. TULIP 1 assessed the effect of anifrolumab in reducing disease activity as measured by the SLE Responder Index 4 (SRI4). Analyses of secondary endpoints show efficacy consistent with TULIP 2 on BICLA response, reduction in oral corticosteroid use, and improvement in skin disease activity.10

TULIP 2, which demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard of care11, randomised 365 eligible patients (1:1) to receive 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 BICLA.  

In addition to the pivotal Phase III TULIP programme, anifrolumab is being evaluated in a Phase III long-term extension trial in SLE and a Phase II trial in lupus nephritis.

Anifrolumab

Anifrolumab is a fully human monoclonal antibody that binds to subunit 1 of the type I interferon receptor, blocking the activity of all type I interferons including IFN-alpha, IFN-beta and IFN-omega.12 Type I interferons are cytokines involved in the inflammatory pathways.13 Between 60% and 80% of adults with SLE have an increased type I interferon gene signature, which has been shown to correlate with disease activity.13,14

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 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, and our inhaled and biologic medicines reached more than 53 million patients in 2019. Building on a 50-year heritage, the Company aims to transform the treatment of asthma and chronic obstructive pulmonary disease (COPD) by driving earlier biology-led treatment, eliminating preventable asthma attacks, and removing COPD as a top-three leading cause of death. Our 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 lupus), 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.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of diseases in three therapy areas - Oncology, Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative medicines are used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Twitter @AstraZeneca.

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References

1. Morand E, Furie R, Bruce I, et al. Early and Sustained Responses With Anifrolumab Treatment in Patients With Active Systemic Lupus Erythematosus (SLE) in 2 Phase 3 Trials [oral]. Presented at: The European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020; 3-6 June 2020. Abstract ID: OP0003.

2. Morand E, Furie R, Tanaka Y, et al. Efficacy of Anifrolumab in Active Systemic Lupus Erythematosus: Patient Subgroup Analysis of BICLA Response in 2 Phase 3 Trials [oral]. Presented at: The European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020; 3-6 June 2020. Abstract ID: OP0049.

3. Furie R, Morand E, Askanase A, et al. Flare Assessments in Patients With Active Systemic Lupus Erythematosus (SLE) Treated With Anifrolumab in 2 Phase 3 Trials [Poster]. Presented at: The European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020); 3-6 June 2020. Abstract ID: SAT0174.

4. Samnaliev M, Barut V, Weir S, et al. Health Care Utilization and Costs in Adults With Systemic Lupus Erythematosus in the United Kingdom: A Real-World Observational Retrospective Cohort Study.  [Poster]. Presented at: The European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020; 3-6 June 2020. Abstract ID: THU0550.

5. Langham J, Barut V, Samnaliev M, et al. Disease Severity, Comorbid Conditions, Treatment Patterns, and Flares in Adults With Systemic Lupus Erythematosus in the United Kingdom: A Real-World Observational Retrospective Cohort Analysis. [Poster] Presented at: The European League Against Rheumatism, EULAR, European E-Congress of Rheumatology 2020; 3-6 June 2020. Abstract ID: SAT0216.

6. The Lupus Foundation of America. What is Lupus?. Available at https://www.lupus.org/resources/what-is-lupus. Accessed June 2020.

7. ACR. Guidelines for referral and management of systemic lupus erythematosus in adults. American College of Rheumatology Ad Hoc Committee on Systemic Lupus Erythematosus Guidelines. Arthritis & Rheumatism. 1999; 42; 1785-1796. Accessed June 2020.

8. Nossent J, Cikes N, Kiss E, et al. Current causes of death in systemic lupus erythematosus in Europe, 2000-2004: relation to disease activity and damage accrual. Lupus. 2007; 16:309-317.

9. Mahieu, M. A., Strand, V, Simon, Lee, S.S et al. A critical review of clinical trials in systemic lupus erythematosus. Lupus. 2016;25(10);1122–1140. Accessed June 2020.

10. Furie R, Morand E, Bruce I, et al. Anifrolumab: Type I Interferon Inhibitor Anifrolumab in Active Systemic Lupus Erythematosus (TULIP-1): a Randomised, Controlled Phase 3 Trial, Lancet Rheumatology 2019; doi.org/10.1016/S2665-9913(19)30076-1. Accessed June 2020.

11. Morand E, Furie R, Tanaka Y, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. New England Journal of Medicine. 2020;382:211-221. doi: 10.1056/NEJMoa1912196. Accessed June 2020.

12. Furie R, Khamashta M, Merrill J T, et al. Anifrolumab, an Anti–Interferon‐α Receptor Monoclonal Antibody, in Moderate‐to‐Severe Systemic Lupus Erythematosus. Arthritis & Rheumatology. 2017;69(2);376-386. Accessed June 2020.

13. Lauwerys BR, Ducreux J, Houssiau FA. Type I interferon blockade in systemic lupus erythematosus: where do we stand?. Rheumatology. 2013;53(8);1369-1376.

14. Crow, M. K, Type I Interferon in the Pathogenesis of Lupus, The Journal of Immunology. 2014;192(12);5459-5468. Accessed June 2020.