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 program 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 effect 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. SAPHNELOisthe 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, SAPHNELOwas 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),³IRIS (Active Proliferative LN),⁴AZALEA (SLE in China),²⁰ and BLOSSOM (pediatric 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,^23,24Japan²⁵ 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

SAPHNELO IMPORTANT SAFETY INFORMATION

CONTRAINDICATION

Known history of anaphylaxis with SAPHNELO.

WARNINGS AND PRECAUTIONS

• Serious Infections: Serious and sometimes fatal infections have occurred in patients receiving immunosuppressive agents, including SAPHNELO. SAPHNELO increases the risk of respiratory infections and herpes zoster. Use caution in patients with severe or chronic infections. Avoid initiating treatment during an active infection and consider interrupting therapy in patients who develop a new infection during treatment
• Hypersensitivity Reaction Including Anaphylaxis: Serious hypersensitivity reactions (including anaphylaxis) have been reported following SAPHNELO administration. Events of angioedema have also been reported. Other hypersensitivity reactions and infusion-related reactions have occurred following administration of SAPHNELO. SAPHNELO should be administered by healthcare providers prepared to manage hypersensitivity reactions, including anaphylaxis and infusion-related reactions, if they occur. Immediately interrupt administration and initiate appropriate therapy if a serious infusion-related or hypersensitivity reaction (e.g., anaphylaxis) occurs
• Malignancy: There is an increased risk of malignancies with the use of immunosuppressants. The impact of SAPHNELO on the potential development of malignancies is not known
• Immunization: Avoid the use of live or live-attenuated vaccines in patients treated with
• Use With Biologic Therapies: SAPHNELO is not recommended for use in combination with other biologic therapies, including B-cell targeted therapies

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥5%) are nasopharyngitis, upper respiratory tract infections, bronchitis, infusion-related reactions, herpes zoster and cough.

In the controlled clinical trials, the incidence of infusion-related reactions was 9.4% in patients while on treatment with SAPHNELO and 7.1% in patients on placebo. Infusion-related reactions were mild to moderate in intensity; the most common symptoms were headache, nausea, vomiting, fatigue, and dizziness.

USE IN SPECIFIC POPULATIONS

Pregnancy: A pregnancy exposure registry monitors pregnancy outcomes in women exposed to SAPHNELO during pregnancy. For more information about the registry or to report a pregnancy while on SAPHNELO, contact AstraZeneca at 1-877-693-9268.

There are insufficient data on the use of SAPHNELO in pregnant women to establish whether there is drug-associated risk for major birth defects or miscarriage. Advise female patients to inform their healthcare provider if they intend to become pregnant during therapy, suspect they are pregnant or become pregnant while receiving SAPHNELO.

Lactation: No data are available regarding the presence of SAPHNELO in human milk, the effects on the breastfed child, or the effects on milk production.

Pediatric Use: The safety and efficacy of SAPHNELO in pediatric patients less than 18 years of age has not been established.

INDICATION

SAPHNELO is indicated for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE), who are receiving standard therapy.

Limitations of Use: The efficacy of SAPHNELO has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Use is not recommended in these situations.

Please see full Prescribing Information, including Patient Information.

You may report side effects related to AstraZeneca products.

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. 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.

AstraZeneca
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

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