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SAPHNELO Consistently Reduces Systemic Lupus Erythematosus Disease Activity Regardless of Disease Duration and Prior Treatment

AZN | November 1, 2021

New subgroup analyses from the TULIP Phase III clinical trial program showed SAPHNELO (anifrolumab), a first-in-class type I interferon antagonist, in addition to standard therapy, resulted in a greater reduction in systemic lupus erythematosus (SLE) disease activity regardless of disease duration, standard therapy type and prior treatment, compared to standard therapy alone. The data will be presented at ACR Convergence 2021, the annual meeting of the American College of Rheumatology (ACR), from 5 to 9 November 2021.

A post-hoc analysis from the pooled TULIP-1 and -2 Phase III trials showed consistent efficacy of SAPHNELO in adult patients with moderate to severe SLE both with recently diagnosed and established disease. Treatment with SAPHNELO also resulted in a consistent reduction in disease activity, irrespective of standard therapy at baseline, including oral corticosteroids (OCS), antimalarials and/or immunosuppressants. Further, SAPHNELOprovided a consistent benefit across efficacy endpoints over standard therapy alone amongst patients with or without prior biologic exposure.

SLE is a complex autoimmune condition that can affect any organ, and patients often experience debilitating symptoms, long-term organ damage and poor health-related quality of life. Treating lupus can be difficult. It can take months, or even years, to find the right combination of treatment options. Despite advances in therapies, the control of disease activity in SLE remains suboptimal. Long-term use of OCS, often used as standard therapy to treat lupus symptoms, is associated with organ damage and significant comorbidities.

Professor Susan Manzi, Allegheny Health Network, PA, US, said: “We need to evolve how lupus is treated by considering biologics earlier and more routinely in patients with uncontrolled disease, particularly those who are taking high doses of oral corticosteroids, which can be damaging long-term. These new analyses are compelling because they demonstrate anifrolumab can consistently reduce disease activity in a range of patients with moderate to severe disease, regardless of their prior treatment or disease onset.”

Micki Hultquist, Global Franchise Head, SAPHNELO, AstraZeneca, said: “These data add to our understanding of SAPHNELO’s compelling clinical profile across a range of patients in areas of unmet need. With SAPHNELO as the first new treatment in systemic lupus erythematosus approved in over a decade, we’ve advanced the science and are focused on challenging current treatment expectations in this often-debilitating disease.”

Results* from the new pooled analyses of the Phase III TULIP program at ACR 2021 include:

Study	Summary
Anifrolumab Results in Clinical Benefit Regardless of SLE Disease Duration: Post Hoc Analysis of Data From 2 Phase 3 Trials (abstract #: 1741)	Patients diagnosed within the last two years and those with established disease experienced a similar benefit with SAPHNELO (14.4% improvement over standard therapy alone and 17.1%, respectively, as assessed by the BILAG–based Composite Lupus Assessment, or BICLA, at week 52)
SLE Treatment History and Anifrolumab Efficacy by Baseline Standard Therapies in Patients With SLE from 2 Phase 3 Trials (abstract #: 1739)	Patients were separated into subgroups depending on which standard therapies they were receiving at baseline: OCS (82.0%), antimalarials (70.2%), and/or immunosuppressants (48.2%), with most patients receiving combinations of two or more types of standard therapy SAPHNELO was associated with consistently higher BICLA response rates than standard of care alone, regardless of the type of baseline standard therapy use
Efficacy of Anifrolumab in Patients With SLE Previously Treated With Biologics: Post Hoc Analysis of Pooled Data from 2 Phase 3 Trials (abstract #: 1740)	Biologic-naïve patients in the trials who received SAPHNELO saw similar benefits across efficacy endpoints (measures of comprehensive disease activity, OCS taper and flare rate), to those previously treated with other biologics

*Analyses were descriptive only; no formal hypotheses were tested.

The adverse reactions that occurred more frequently in patients who received SAPHNELO in clinical trials included nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster and cough.

SAPHNELO is approved in the US and Japan and is under regulatory review in the EU for the treatment of SLE. A Phase III trial in SLE using subcutaneous delivery has been initiated and additional Phase III trials are planned for lupus nephritis, cutaneous lupus erythematosus and myositis.

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 (eg, 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 SAPHNELO
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 receivingstandard 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.

Notes

Financial considerations

AstraZeneca acquired global rights to SAPHNELO through an exclusive license and collaboration agreement with Medarex, Inc. in 2004. The option for Medarex to co-promote the product expired on its acquisition by Bristol-Myers Squibb (BMS) in 2009. Under the agreement AstraZeneca will pay BMS a low to mid-teens royalty for sales dependent on geography.

Systemic lupus erythematosus

SLE 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.

TULIP-1, TULIP-2, MUSE

All three trials for SAPHNELO(TULIP-1, TULIP-2 and MUSE) were randomized, double-blinded, placebo-controlled trials in adult patients with moderate to severe SLE who were receiving standard therapy.Standard therapy included at least one of the following: OCS, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).

The pivotal TULIP (Treatment of Uncontrolled Lupus via the Interferon Pathway) Phase III program included two trials, TULIP-1 and TULIP-2, that evaluated the efficacy and safety of SAPHNELOversus placebo. TULIP-2 demonstrated superiority across multiple efficacy endpoints versus placebo with both arms receiving standard therapy. In the trial, 362 eligible patients were randomized (1:1) and received a fixed-dose intravenous infusion of 300mg SAPHNELOor placebo every four weeks. TULIP-2 assessed the effect of SAPHNELOin reducing disease activity as measured by the BILAG-Based Composite Lupus Assessment (BICLA) scale. In TULIP-1, 457 eligible patients were randomized (1:2:2) and received a fixed-dose intravenous infusion of 150mg SAPHNELO,300mg SAPHNELOor 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.

The MUSE Phase II trial evaluated the efficacy and safety of two doses of SAPHNELOversus placebo. In MUSE, 305 adults were randomized and received a fixed-dose intravenous infusion of 300mg SAPHNELO, 1,000mg SAPHNELOor placebo every four weeks, in addition to standard therapy, for 48 weeks. The trial showed improvement versus placebo across multiple efficacy endpoints with both arms receiving standard therapy.

In SLE, along with the pivotal TULIP Phase III program, SAPHNELO continues to be evaluated in a long-term extension Phase III trial and a Phase III trial assessing subcutaneous delivery. In addition, AstraZeneca is exploring the potential of SAPHNELOin a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus and myositis.

Post-hoc TULIP subgroup analysis will be presented at ACR 2021: Clinical benefit of anifrolumab regardless of SLE disease duration

Efficacy endpoint

Results by disease onset subgroup

SAPHNELO added to standard therapy versus placebo plus standard therapy (95% CI; nominal p-value)

Recent onset (<2 years)

Established

BICLA response at Week 52

SAPHNELO: 47.6%

Placebo: 33.2%

∆14.4% (-2.2-31.1; p=0.090)

SAPHNELO: 47.4%

Placebo: 30.3%

∆17.1% (9.3-24.8; p<0.001)

Post-hoc TULIP subgroup analyses will be presented at ACR 2021: SLE treatment history and anifrolumab efficacy by baseline standard therapies

Baseline therapy subgroup	BICLA results SAPHNELO added to standard therapy versus placebo plus standard therapy (95% CI; nominal p-value)
Overall	SAPHNELO: 47.5% Placebo: 30.8% ∆16.6% (9.7-23.6; p<0.001)
OCS only	SAPHNELO: 45.5% Placebo: 23.7% ∆21.8% (2.4-41.2; p=0.028)
Antimalarial only	SAPHNELO: 43.8% Placebo: 28.9% ∆14.9% (-7.4-37.2; p=0.189)
Immunosuppressant only	SAPHNELO: 78.4% Placebo: 27.6% ∆50.8% (-0.07-100.0; p=0.053)
OCS + antimalarial	SAPHNELO: 45.1% Placebo: 33.8% ∆11.3% (-2.0-24.6; p=0.096)
OCS + immunosuppressant	SAPHNELO: 46.0% Placebo: 28.9% ∆17.1% (-1.4-35.7; p=0.070)
Antimalarial + immunosuppressant	SAPHNELO: 40.0% Placebo: 33.0% ∆6.9% (-24.0-37.9; p=0.660)
OCS + antimalarial + immunosuppressant	SAPHNELO: 53.6% Placebo: 32.2% ∆21.4% (7.4-35.4; p=0.003)

Post-hoc TULIP subgroup analyses will be presented at ACR 2021: Efficacy of anifrolumab in patients with SLE previously treated with biologics

Efficacy endpoint

Results by biologic treatment subgroup

SAPHNELO added to standard therapy versus placebo plus standard therapy (95% CI)

Biologic experienced

Biologic naïve

BICLA response at Week 52

SAPHNELO: 44.1%

Placebo: 24.6%

∆19.4% (4.2-34.6)

SAPHNELO: 49.1%

Placebo: 32.4%

∆16.6% (8.8-24.5)

SRI(4) response at Week 52

SAPHNELO: 53.4%

Placebo: 28.1%

∆25.3% (9.9-40.7)

SAPHNELO: 52.3%

Placebo: 43.2%

∆9.1% (1.0-17.2)

Sustained OCS reduction at Week 40-52

SAPHNELO: 52.9%

Placebo: 28.2%

∆24.7% (2.0-47.4)

SAPHNELO: 50.0%

Placebo: 32.5%

∆17.5% (6.6-28.4)

Annualized flare rate through Week 52

SAPHNELO: 0.48

Placebo: 0.74

*0.65 (1.05-0.41)

SAPHNELO: 0.51

Placebo: 0.64

*0.78 (1.02-0.60)

∆ = treatment difference, percentage points; * = rate ratio
CI: confidence interval
BICLA: British Isles Lupus Assessment Group (BILAG)-based combined lupus assessment
SRI(4): SLE Responder Index

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. Type I IFNs such as IFN-alpha, IFN-beta and IFN-kappa are cytokines involved in regulating the inflammatory pathways implicated in SLE. The majority of adults with SLE have increased type I IFN signaling, which is associated with increased disease activity and severity.

AstraZeneca in Respiratory & Immunology

Respiratory & Immunology, part of BioPharmaceuticals, is one of AstraZeneca’s main disease 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.

About 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 100 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 Twitter @AstraZenecaUS.

Z4-38947 Last Updated 10/21