AstraZeneca announces start of recruitment in two new Phase III trials evaluating Saphnelo – in cutaneous lupus erythematosus (LAVENDER) and in idiopathic inflammatory myopathies (JASMINE)

Saphnelo now being investigated in four Phase III clinical trials beyond systemic
lupus erythematosus

AstraZeneca today announced the initiation of two Phase III trials, LAVENDER and JASMINE, investigating Saphnelo (anifrolumab) in two autoimmune diseases. The studies are being conducted in patients with cutaneous lupus erythematosus (CLE) and idiopathic inflammatory myopathies (IIM) (namely polymyositis and dermatomyositis) respectively.1,2 These studies follow additional Phase III trials initiated in systemic sclerosis (SSc) and lupus nephritis (LN) as part of a broad clinical development programme investigating Saphnelo in type I interferon-driven, immune-mediated diseases.3,4

High unmet need remains in all conditions being investigated as their pathology is poorly understood.5-8 In these initiated trials, the efficacy of anifrolumab is being evaluated on abnormalities in the type I interferon (IFN) immune pathway.1,2 Specifically for patients with CLE and IIM, treatment options tend to be based on broad immunosuppressants and corticosteroids, which are non-disease-specific and associated with significant side effects.9-11 Quality of life for these patients can be severely impaired, particularly with respect to emotional well-being.12,13 To date, no targeted therapeutic agents have been approved specifically for patients with CLE, and though intravenous immunoglobulin has been approved for the treatment of dermatomyositis, a targeted treatment for polymyositis has not yet been approved.6,13-15

Paula Eichenbrenner, Executive Director, The Myositis Association said: “Living with a rare autoimmune disease such as myositis can cause debilitating symptoms including muscle weakness, pain, extreme tiredness and difficulty breathing. Myositis significantly impacts quality of life for affected individuals and families. With very few treatment options currently available, our community welcomes this new research which we hope will advance standards of care."

Professor Ruth Ann Vleugels, Heidi and Scott C. Schuster Distinguished Chair in Dermatology and Director, Connective Tissue Disease Program, Brigham and Women's Hospital/Harvard Medical School said:  "With the type I interferon pathway expected to play a key role in the pathophysiology of cutaneous lupus erythematosus and idiopathic inflammatory myopathies, these new studies with anifrolumab are incredibly encouraging, and mark an important step forward in investigating the potential role of anifrolumab in treating these diseases."

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "The initiation of the LAVENDER and JASMINE Phase III trials demonstrates our ongoing commitment to address the major unmet needs in these disease areas. Saphnelo is the first and only type I interferon receptor antagonist approved for systemic lupus erythematosus, with proven increased rates of remission versus standard therapy and sparing patients from glucocorticoid use. We look forward to exploring how anifrolumab’s mechanism of action might affect other type I interferon-driven diseases."

In SLE, Saphnelo was evaluated in a long-term extension (LTE) Phase III trial. In the post hoc analysis of the LTE trial, a numerically greater number of patients treated with Saphnelo achieved remission (30.3%; n=58/194) versus those treated with standard therapy alone (18.3%; n=12/65) at Week 208.16-18 Saphnelo was generally well-tolerated and no new safety concerns were found.19

Saphnelo is also being investigated in DAISY (SSc),3 IRIS (Active Proliferative LN),4 AZALEA (SLE in China),20 and BLOSSOM (paediatric SLE),21 and continues to be studied in a Phase III trial assessing subcutaneous delivery, including an open-label extension.22 See the clinicaltrials.gov pages to find out more about these trials.

Saphnelo is currently approved for the treatment of moderate to severe systemic lupus erythematosus (SLE) in multiple countries, including the US,23,24 Japan25 and Europe,26,27 with regulatory reviews ongoing in other countries worldwide. Saphnelo was granted Orphan Drug Designation (ODD) by the US Food and Drug Administration for the treatment of SSc in October 201328 and for myositis in December 2022.29

Notes

Cutaneous lupus erythematosus

Cutaneous lupus erythematosus (CLE) is an autoimmune disease with many subtypes caused by abnormalities in multiple immune pathways, including type I interferon.6,12,30 CLE affects approximately 70 people out of every 100,000.6 It typically manifests in the skin.6,12 Its symptoms range from limited cutaneous disease to severe and life-threatening systemic disease due to vital-organ involvement.13 It has a profoundly negative impact on patient quality of life, causing damage, disfigurement, a negative impact on mental health and fatigue.12 There is a need for newer, more effective, targeted therapies for CLE.30

Idiopathic inflammatory myopathies

Idiopathic inflammatory myopathies (IIM) refers to a group of rare acquired progressive autoimmune connective tissue disorders characterised by chronic muscle weakness, low muscular endurance, and muscle tissue inflammation.15 IIM affects 1-8 people out of every 100,000.15 These diseases have high morbidity and mortality rates, with 4 of 5 myositis patients experiencing disability in body care and mobility in the five years post-diagnosis, and disease-related deaths occurring in up to 45% of patients with IIM.31 IIM is an SLE-related disease characterised by strong type I IFN involvement.32,33 The diseases are characterised by increased type I IFN signalling34 and substantial unmet medical need for novel treatments with disease-specific mechanisms of action.31 Corticosteroids are currently the mainstay of myositis treatment, but their use is associated with significant side effects.6,15

Systemic sclerosis

Systemic sclerosis (SSc), also known as scleroderma, is a chronic progressive multi-organ disease characterised by increased type I IFN signalling, functional and structural abnormalities of small blood vessels and scarring (fibrosis) of the skin and internal organs.35,36 It has the highest mortality in rheumatology,37 and disease progression results in multi-organ damage primarily in the first six years following diagnosis.38 Currently, there are no treatments for the broader systemic manifestations of the disease.

Lupus nephritis
Lupus nephritis (LN) is a serious complication of SLE that occurs when the immune system mistakenly attacks the kidneys, which, if left untreated, can ultimately lead to kidney failure.39 LN is more common in women than in men, and there is a higher prevalence and severity of the disease among African American, Asian and Hispanic women between 15-44, who tend to develop the disease earlier and experience more serious complications.39

LAVENDER (NCT06015737)

The LAVENDER Phase III trial is a multinational, randomised, double-blind, placebo-controlled, study to evaluate the efficacy and safety of Saphnelo (anifrolumab) in adults with chronic and/or cutaneous lupus erythematosus. The primary objective of the study is to evaluate the efficacy of anifrolumab, compared to placebo, in reducing skin disease in approximately 460 adult participants.1

JASMINE (NCT06455449)

The JASMINE Phase III trial is a multinational, randomised, double-blind, placebo-controlled study expected to enrol approximately 240 patients aged between 18 to 75 years with polymyositis. The aim of the study is to evaluate the efficacy and safety of subcutaneous Saphnelo (anifrolumab) in adult patients with moderate to severe idiopathic inflammatory myopathies receiving standard of care treatment.2

IRIS (NCT05138133)
The IRIS Phase III trial is a two-year, multicentre, multinational, randomised, double-blind, placebo-controlled study expected to enrol up to 360 participants aged 18 to 70.4 The aim of the study is to evaluate the efficacy and safety of Saphnelo versus placebo when added to standard therapy (consisting of mycophenolate mofetil and glucocorticoids) in adults diagnosed with active Class III or IV LN (with or without concomitant Class V).4 Active LN will be confirmed by kidney biopsy during screening visits using the 2003 International Society of Nephrology/Renal Pathology Society criteria, and clinically active kidney disease.4

DAISY (NCT05925803)

The DAISY Phase III trial is a multinational, randomised, double-blind, placebo-controlled study expected to enrol approximately 306 patients aged between 18 to 70 years with systemic sclerosis. The aim of the study is to evaluate the efficacy and safety of subcutaneous Saphnelo (anifrolumab) in adult patients with systemic sclerosis with or without standard therapy.3

Phase III TULIP clinical programme
All three TULIP trials for Saphnelo (TULIP-1, TULIP-2, and TULIP-LTE) were randomised, double-blinded, placebo-controlled trials in patients with moderate-to-severe SLE who were receiving standard therapy. The placebo arm of the trial included at least one of the following standard therapies: oral corticosteroids, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).19,40,41

The longest placebo-controlled clinical trial performed in SLE to date,25,42 TULIP-LTE investigated the long-term safety and tolerability of Saphnelo compared with placebo in 559 enrolled patients with moderate to severe SLE who had previously completed a Phase III study for an additional three years.19 In the post hoc analysis presented at the European Lupus Meeting, 369 patients (anifrolumab 300 mg, n=257; placebo, n=112) who continued treatment in TULIP-LTE were analysed for the 4-year TULIP+LTE period.17

Saphnelo

Saphnelo (anifrolumab) is a fully human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, blocking the activity of type I IFN.24 Type I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines involved in regulating the inflammatory pathways implicated in several immune-driven diseases.43-48

Our research in, and understanding of, the association of elevated IFN-1 signalling with several immune mediated conditions is guiding investigation of anifrolumab in conditions such as SSC3 and IIM,2 where increased type I IFN signalling is observed, and patients are likely to benefit from targeted treatment.47,49

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of AstraZeneca BioPharmaceuticals is a key disease area and growth driver to the Company.

AstraZeneca is an established leader in respiratory care with a 50-year heritage and a growing portfolio of medicines in immune-mediated diseases. The Company is committed to addressing the vast unmet needs of these chronic, often debilitating, diseases with a pipeline and portfolio of inhaled medicines, biologics and new modalities aimed at previously unreachable biologic targets. Our ambition is to deliver life-changing medicines that help eliminate COPD as a leading cause of death, eliminate asthma attacks and achieve clinical remission in immune-mediated diseases.

AstraZeneca
AstraZeneca (LSE/STO/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca’s innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on social media @AstraZeneca

Contacts
For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here.

References

  1. Clinicaltrials.gov. A 2-stage, Phase III Study to Investigate the Efficacy and Safety of Anifrolumab in Adults With Chronic and/​or Subacute Cutaneous Lupus Erythematosus (LAVENDER). Available at: https://clinicaltrials.gov/study/NCT06015737 [Last accessed: August 2024].
  2. Clinicaltrials.gov. A Study to Investigate the Efficacy and Safety of Anifrolumab Administered as Subcutaneous Injection and Added to Standard of Care Compared With Placebo Added to Standard of Care in Adult Participants With Idiopathic Inflammatory Myopathies (Polymyositis and Dermatomyositis) (JASMINE). Available at: https://clinicaltrials.gov/study/NCT06455449 [Last accessed: August 2024].
  3. Clinicaltrials.gov. Determine Effectiveness of Anifrolumab In SYstemic Sclerosis (DAISY). Available at: https://clinicaltrials.gov/study/NCT05925803 [Last accessed: August 2024].
  4. ClinicalTrials.gov. Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis (IRIS). Available at: https://www.clinicaltrials.gov/ct2/show/NCT05138133. [Last accessed: August 2024].
  5. Lundberg IE, et al. Idiopathic Inflammatory Myopathies. Nat Rev Dis Primers. 2021;7:87.
  6. Petty AJ, et al. Cutaneous Lupus Erythematosus: Progress and Challenges. Curr Allergy Asthma Rep. 2020;20:12.
  7. Kuhn A, et al. The skin in autoimmune diseases–Unmet needs. Autoimmun Rev. 2016;15:948-954.
  8. Meyer A, et al. Idiopathic inflammatory myopathies: state of the art on clinical practice guidelines. RMD Open. 2019;4(Suppl 1):e000784.
  9. Okon LG & Werth VP. Cutaneous Lupus Erythematosus: Diagnosis and treatment. Best Pract Res Clin Rheumatol. 2013;27:391-404.
  10. Shi H, et al. Treatment of cutaneous lupus erythematosus: current approaches and future strategies. Curr Opin Rheumatol. 2020;32:208-214.
  11. Barsotti S & Lundberg IE. Current Treatment for Myositis. Curr Treat Options in Rheum. 2018;4:299-315.
  12. Werth VP et al. Trial of Anti-BDCA2 Antibody Litifilimab for Cutaneous Lupus Erythematosus. N Engl J Med. 2022;387:321-331.
  13. Vale ESCD and Garcia LC. Cutaneous lupus erythematosus: a review of etiopathogenic, clinical, diagnostic and therapeutic aspects. An Bras Dermatol. 2023;98:355-372.
  14. FDA. Octagam 10% Prescribing Information. Available at: https://www.fda.gov/media/70911/download. [Last accessed: August 2024].
  15. Sarwar A, et al. Polymyositis. [Updated 2023 Feb 7]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan. Available from: https://www.ncbi.nlm.nih.gov/books/NBK563129/ [Last accessed: August 2024]
  16. AstraZeneca plc. AstraZeneca presents new post-hoc analysis from Phase III TULIP long-term extension trial at the European Lupus Meeting 2024. Available at: https://www.astrazeneca.com/media-centre/medical-releases/saphnelo-demonstrates-higher-rates-of-remission-in-patients-with-systemic-lupus-erythematosus-compared-to-standard-therapy-alone-over-4-year-period.html [Last accessed: August 2024]
  17. Vollenhoven RV, et al. DORIS remission in patients with SLE treated with anifrolumab or placebo during the 4-year TULIP-LTE trial: Post hoc analysis [Poster]. Presented at the European Lupus Meeting 2024 (19-22 March 2024).
  18. AstraZeneca Data on File REF-216754.
  19. ClinicalTrials.gov. Long Term Safety of Anifrolumab in Adult Subjects With Active Systemic Lupus Erythematosus (TULIP SLE LTE). Available at: https://clinicaltrials.gov/study/NCT02794285 [Last accessed: August 2024].
  20. ClinicalTrials.gov. Anifrolumab Asian PhIII Efficacy Study for Systemic Lupus Erythematosus (SLE). Available at: https://clinicaltrials.gov/ct2/show/NCT04931563. [Last accessed: August 2024].
  21. ClinicalTrials.gov. An Efficacy and Safety Study of Intravenous Anifrolumab to Treat Systemic Lupus Erythematosus in Pediatric Participants (SLE). Available at: https://clinicaltrials.gov/study/NCT05835310. [Last accessed: August 2024].
  22. ClinicalTrials.gov. Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC). Available at: https://clinicaltrials.gov/study/NCT04877691 [Last accessed: August 2024].
  23. AstraZeneca. Saphnelo (anifrolumab) approved in the US for moderate to severe systemic lupus erythematosus. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-approved-in-the-us-for-sle.html# [Last accessed: August 2024].
  24. FDA. Saphnelo Prescribing Information. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761123s003lbl.pdf [Last accessed: August 2024]
  25. AstraZeneca. Saphnelo approved in Japan for systemic lupus erythematosus. Available at: https://www.astrazeneca.com/media-centre/press-releases/2021/saphnelo-approved-in-japan-for-sle.html# [Last accessed: August 2024].
  26. AstraZeneca. Saphnelo approved in the EU for the treatment of moderate to severe systemic lupus erythematosus. Available at: https://www.astrazeneca.com/media-centre/press-releases/2022/saphnelo-approved-in-eu-for-sle.html# [Last accessed: August 2024].
  27. Saphnelo. Summary of Product Characteristics 2022. Available at: https://www.ema.europa.eu/en/documents/product-information/saphnelo-epar-product-information_en.pdf [Last accessed: August 2024].
  28. US Food and Drug Administration, Orphan Drug Designations and Approvals. Available from: https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=299209. [Last accessed: August 2024]
  29. US Food and Drug Administration, Orphan Drug Designations and Approvals. Available from https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=876522. [Last accessed: August 2024]
  30. Sprow G, et al. Emerging Therapies in Cutaneous Lupus Erythematosus. Front Med. 2022;9:968323.
  31. Bronner IM, et al. Long-term outcome in polymyositis and dermatomyositis. Ann Rheum Dis. 2006;65:1456-1461.
  32. Pauling JD, et al. The clinicoserological spectrum of inflammatory myopathy in the context of systemic sclerosis and systemic lupus erythematosus. Indian J Rheumatol. 2020;15(6):81-90. doi:10.4103/injr.injr_136_20.
  33. Walsh RJ, et al. Type I interferon-inducible gene expression in blood is present and reflects disease activity in dermatomyositis and polymyositis. Arthritis Rheum. 2007;56(11):3784-92
  34. Crow MK, et al. Type I Interferons in Autoimmune Disease. Annu Rev Pathol. 2019;14:369-393.
  35. Papadimitriou TI, et al. Therapeutic Options for Systemic Sclerosis: Current and Future Perspectives in Tackling Immune-Mediated Fibrosis. Biomedicines. 2022;10(2):316.
  36. Adigun R, et al. Systemic Sclerosis. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK430875/ [Last accessed August 2024].
  37. Editorial. Systemic sclerosis: advances and prospects. The Lancet. 2017;390:1624
  38. Tay T, et al. Early Accrual of Organ Damage in Systemic Sclerosis: Rationale for Development of a Disease Damage Index. J Scleroderma Relat Disord. 2017;2(2):127-134. doi:10.5301/jsrd.5000239
  39. The Lupus Foundation of America. What is Lupus Nephritis? Available at: https://www.lupus.org/resources/what-is-lupus-nephritis [Last accessed: August 2024]
  40. ClinicalTrials.gov. Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus. Available at: https://clinicaltrials.gov/study/NCT02446912 [Last accessed: August 2024].
  41. ClinicalTrials.gov. Efficacy and Safety of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus. Available at: https://clinicaltrials.gov/study/NCT02446899 [Last accessed: August 2024].   
  42. AstraZeneca. Saphnelo demonstrates higher rates of remission in patients with systemic lupus erythematosus compared to standard therapy alone over 4-year period. Available at: https://www.astrazeneca.com/media-centre/medical-releases/saphnelo-demonstrates-higher-rates-of-remission-in-patients-with-systemic-lupus-erythematosus-compared-to-standard-therapy-alone-over-4-year-period.html [Last accessed: August 2024].
  43. Lauwerys BR, et al. Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatol. 2014;53:1369-1376.
  44. Sarkar MK, et al. Photosensitivity and type I IFN responses in cutaneous lupus are driven by epidermal-derived interferon kappa. Ann Rheum Dis. 2018;77:1653-1664.
  45. Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol. 2019;10:325.
  46. Mai L, et al. The baseline interferon signature predicts disease severity over the subsequent 5 years in systemic lupus erythematosus. Arthritis Res Ther. 2021;23:29.
  47. López de Padilla CM, et al. The Type I Interferons: Basic Concepts and Clinical Relevance in Immune-mediated Inflammatory Diseases. Gene. 2016;576 (101):14-21.
  48. Rönnblom L, et al. Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med. 2019;6(1):e000270.
  49. Kakkar V, et al. Type 1 interferon activation in systemic sclerosis: a biomarker, a target or the culprit. Curr Opin Rheumatol. 2022;34(6):357-364.

Veeva ID: Z4-68777
Date of Preparation: September 2024