https://www.astrazeneca-us.com/media/press-releases/2023/saphnelo-data-show-patients-are-more-likely-to-achieve-and-sustain-remission-in-systemic-lupus-erythematosus-compared-to-standard-therapy-alone.html#:~:text=SAPHNELO%20data%20show%20patients%20are,compared%20to%20standard%20therapy%20alone

AstraZeneca presents new evidence from TULIP Phase III program as part of 18 total abstracts across its Immunology portfolio at ACR 2023

 

A new post-hoc analysis of the TULIP Phase III program provides evidence across four years that remission is an achievable goal with SAPHNELO (anifrolumab-fnia), a first-in-class biologic for patients living with systemic lupus erythematosus (SLE).1 This data will be presented at ACR Convergence 2023, the annual meeting of the American College of Rheumatology (ACR), in San Diego, California, from November 10th-15th, 2023.

SLE is a serious and complex autoimmune condition that can affect any organ, and patients often experience inadequate disease control.2,3 In lupus, remission is associated with reduced organ damage, fewer flares, reduced hospitalization, reduced mortality and improved health-related quality of life.4,5

Ronald van Vollenhoven, Chair of Rheumatology and Director of the Amsterdam Rheumatology Center in Amsterdam, the Netherlands and abstract lead author said: "Despite advances in therapies for systemic lupus erythematosus, few patients experience remission, and their disease activity is often not adequately controlled by standard therapy. Compared to standard therapy, with anifrolumab we're seeing higher rates of patients with no disease activity while bringing oral corticosteroid use to the guidelines-recommended threshold, a real step forward for SLE treatment."

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "This data adds to our understanding of SAPHNELO's compelling clinical profile in reducing disease activity across organ systems while lowering the use of oral corticosteroids, and now meeting a higher standard of disease control, with remission. With SAPHNELO, and across our portfolio in Immunology, we remain focused on our ambition to challenge current treatment expectations and help establish remission as an achievable treatment goal for as many patients as possible."

Remission was defined using the DORIS criteria (Definition of Remission in SLE): no disease activity assessed by two measures of disease activity across organ systems (total SLEDAI-2K, or "Systemic Lupus Erythematosus Disease Activity Index 2000" score, and the physician global assessment), oral corticosteroid (OCS) dose of <5 mg per day, and no use of restricted medicines.1

In this post-hoc analysis, a numerically greater number of patients treated with SAPHNELO achieved remission vs. standard therapy alone: At the end of the four-year TULIP program (Week 208), 33% (n=63/194) of patients treated with SAPHNELO were in remission compared with 21.4% (n=14/65) on standard therapy alone. This was an increase from 18.7% (n=45/254) of patients treated with SAPHNELO who achieved remission at the end of the first year of the TULIP program (Week 52) compared with 8.6% (n=9/108) of those on standard therapy. In addition, patients treated with SAPHNELO spent a greater percentage of time in remission (17.2% vs. 8.3%; 95% CI 3.2-14.5; p=0.0022) and were more likely to sustain remission for three or more visits compared with standard therapy alone (30.2% vs. 17.2%; 95% CI 1.2-3.6; p=0.0127). SAPHNELO is the first biologic with remission data from a four-year placebo-controlled trial.

Recent recommendations from the European Alliance of Associations for Rheumatology (EULAR) advise taking an OCS-sparing approach to the management of SLE, with early use of biologics to achieve remission or lower disease activity, preserve renal function, and reduce flares and organ damage.6

Key additional data from AstraZeneca at ACR include:

• Additional analyses from the TULIP program, showing SAPHNELO treatment was associated with reducing disease activity across multiple organ systems,7 including fewer patients with renal involvement,8 and improvements in physical, mental, and quality of life measures with long-term use;
• Positive late-breaking full results from the FASENRA (benralizumab) MANDARA Phase III trial, the first head-to-head trial of biologics to treat eosinophilic granulomatosis with polyangiitis (EGPA).10

AstraZeneca Respiratory & Immunology pipeline and portfolio highlighted in 18 abstracts at ACR Convergence 2023

Key data from AstraZeneca:

Presenting author	Abstract title	Presentation details
SAPHNELO (anifrolumab-fnia)
Furie, RA	Renal Involvement in Patients with Systemic Lupus Erythematosus Treated with Anifrolumab Compared with Placebo over a 4-Year Period	0582–0608 Poster Session A 12 November 2023 9:00-11:00 PST
Furie, RA	Efficacy of Anifrolumab in Systemic Lupus Erythematosus by Overall and Organ-Specific SLEDAI-2K Improvements: Results from the Randomized, Placebo-Controlled Phase 3 Long-Term Extension Study	0582–0608 Poster Session A 12 November 2023 9:00-11:00 PST
Strand, V	Evaluation of Anifrolumab Treatment Responses by the Short Form 36 Health Survey Version 2 in SLE: A Post Hoc Analysis of the Placebo-Controlled Phase 3 Long-Term Extension Trial	0582–0608 Poster Session A 12 November 2023 9:00-11:00 PST
Aringer, M	Real-World Treatment Patterns in Patients with Systemic Lupus Erythematosus: An Analysis of the SLE Prospective Observational Cohort Study (SPOCS)	0582–0608 Poster Session A 12 November 2023 9:00-11:00 PST
Hasni, S	Multi-Omic Profiling Reveals Immune Cell Priming Signature Linked to Systemic Lupus Erythematosus Prognosis	Abstract Session 13 November 2023 16:00-17:30 PST
Lim, SS	Using Patient Self-Reported Measures to Predict All-Cause Hospitalization in a Population-Based Lupus Cohort	1200-1220 Poster Session B 13 November 2023 9:00-11:00 PST
Lim, SS	Using Patient-Reported Disease Activity in a Population-Based Cohort to Predict Systemic Lupus Erythematous Hospitalization and Emergency Room Visits	1200-1220 Poster Session B 13 November 2023 9:00-11:00 PST
Kyttaris, V	Characteristics and Prior Treatment Journey of Systemic Lupus Erythematosus (SLE) Patients Who Were Prescribed Anifrolumab – Observations from the American Rheumatology Network (ARN) in the U.S.	1488-1512 Poster Session B 13 November 2023 9:00-11:00 PST
Vollenhoven, RV	Remission Attainment in Patients with Systemic Lupus Erythematosus Treated with Anifrolumab Compared with Placebo over a 4-Year Period	2326–2351 Poster Session C 14 November 2023 9:00-11:00 PST
Furie, RA	Organ Damage Progression in Systemic Lupus Erythematosus: An Analysis of the SLE Prospective Observational Cohort Study (SPOCS)	2257–2325 Poster Session C 14 November 2023 9:00-11:00 PST
Morand, E	Disease Activity Progression in Systemic Lupus Erythematosus: An Analysis of the SLE Prospective Observational Cohort Study (SPOCS)	2257–2325 Poster Session C 14 November 2023 9:00-11:00 PST
Jayne, D	Identification of Urine Metabolites Linked to Disease Activity That Are Modulated by Anifrolumab in a Phase 2 LN Trial Using Untargeted Metabolomics Analysis	2326–2351 Poster Session C 14 November 2023 9:00-11:00 PST
Mamani, IL	Proposal for Defining Moderate and Severe Activity States in Systemic Lupus Erythamatosus. Impact On Flares and Other Outcomes	2257-2325 Poster Session C 14 November 2023 9:00-11:00 PST
FASENRA (benralizumab)
Merkel, PA	Efficacy and Safety of Benralizumab Compared with Mepolizumab in the Treatment of Eosinophilic Granulomatosis with Polyangiitis in Patients Receiving Standard of Care Therapy: Phase 3 MANDARA Study	L14 Late-Breaking Posters 14 November 2023 9:00-11:00 PST
Keogh, KA	Disease Burden of Eosinophilic Granulomatosis with Polyangiitis (EGPA):  A Retrospective Analysis of US Health Insurance Claims Data	1534–1553 Poster Session B 13 November 2023 9:00-11:00 PST
Keogh, KA	Diagnosis Pathways in Patients with Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Retrospective Analysis of US Health Insurance Claims Data	1534–1553 Poster Session B 13 November 2023 9:00-11:00 PST
Chen, S Y	Treatment Patterns for Eosinophilic Granulomatosis with Polyangiitis (EGPA): A Retrospective Analysis of US Health Insurance Claims Data	1534–1553 Poster Session B 13 November 2023 9:00-11:00 PST
Cottin, V	Epidemiology and outcome of eosinophilic granulomatosis with polyangiitis in France	1534-1553 Poster Session B 13 November 2023 9:00-11:00 PST

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.

FASENRA IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Known hypersensitivity to benralizumab or excipients.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions
Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, rash) have occurred after administration of FASENRA. These reactions generally occur within hours of administration, but in some instances have a delayed onset (i.e., days). Discontinue in the event of a hypersensitivity reaction.

Acute Asthma Symptoms or Deteriorating Disease
FASENRA should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Reduction of Corticosteroid Dosage
Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of therapy with FASENRA. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection
It is unknown if FASENRA will influence a patient's response against helminth infections. Treat patients with pre-existing helminth infections before initiating therapy with FASENRA. If patients become infected while receiving FASENRA and do not respond to anti-helminth treatment, discontinue FASENRA until infection resolves.

ADVERSE REACTIONS

The most common adverse reactions (incidence ≥ 5%) include headache and pharyngitis.

Injection site reactions (e.g., pain, erythema, pruritus, papule) occurred at a rate of 2.2% in patients treated with FASENRA compared with 1.9% in patients treated with placebo.

USE IN SPECIFIC POPULATIONS

A pregnancy exposure registry monitors pregnancy outcomes in women exposed to FASENRA during pregnancy. To enroll call 1-877-311-8972 or visit www.mothertobaby.org/fasenra.

The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies such as benralizumab are transported across the placenta during the third trimester of pregnancy; therefore, potential effects on a fetus are likely to be greater during the third trimester of pregnancy.

INDICATION

FASENRA is indicated for the add-on maintenance treatment of patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype.

• FASENRA is not indicated for treatment of other eosinophilic conditions
• FASENRA is not indicated for the relief of acute bronchospasm or status asthmaticus

Please read full Prescribing Information, including Patient Information and Instructions for Use.

You may report side effects related to AstraZeneca products.

Notes

Systemic lupus erythematosus

SLE is an autoimmune disease in which the immune system attacks healthy tissue in the body.3 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.11 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.3,12

Phase III TULIP clinical program

All three TULIP trials for SAPHNELO (TULIP-1, TULIP-2, and TULIP-LTE, or long-term extension) were randomised, double-blinded, placebo-controlled trials in patients with moderate to severe SLE who were receiving standard therapy.13-15 The placebo arm of the trial included at least one of the following standard therapies: OCS, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).16-18

The longest placebo-controlled clinical trial performed in SLE to date,19 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.15 In the post-hoc analysis presented at ACR, 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.1

SAPHNELO

SAPHNELO (anifrolumab-fnia) is a first-in-class, fully human monoclonal antibody that binds to subunit 1 of the type I IFN receptor, blocking the activity of type I IFN.20,21 Type I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines involved in regulating the inflammatory pathways implicated in SLE.22-27 The majority of adults with SLE have increased type I IFN signalling, which is associated with increased disease activity and severity.22,28

SAPHNELO is approved to treat SLE in more than 60 countries worldwide including the US, EU and Japan, with reviews ongoing in other countries. SAPHNELO continues to be evaluated in the TULIP-SC Phase III trial assessing subcutaneous delivery in SLE,29 the AZALEA Phase III trial in SLE in China,30 and the IRIS Phase III trial in lupus nephritis.31 Additional Phase III trials are planned investigating SAPHNELO in diseases where type I IFN plays a key role, including cutaneous lupus erythematosus, systemic sclerosis and myositis.32,33

Eosinophilic granulomatosis with polyangiitis

EGPA, formerly known as Churg-Strauss Syndrome, is a rare, immune-mediated inflammatory disease that is caused by inflammation of small to medium-sized blood vessels.34,35 It is estimated that 118,000 people throughout the world live with EGPA.36

EGPA can result in damage to multiple organs, including lungs, skin, heart, gastrointestinal tract and nerves.34 The most common symptoms and signs include fatigue, weight loss, muscle and joint pain, rashes, nerve pain, sinus and nasal symptoms, and shortness of breath.34,37 Without treatment, the disease may be fatal.34,37

MANDARA

MANDARA was a randomised, double blind, double-dummy, active-controlled, parallel group, multicentre 52-week Phase III trial which compared the efficacy and safety of FASENRA to mepolizumab in adult patients with relapsing or refractory EGPA.38 In the blinded trial, 140 patients were randomised 1:1 (70 per treatment group) to receive either a single 30mg subcutaneous injection of FASENRA or three separate 100mg subcutaneous injections of mepolizumab once every four weeks.38

The primary endpoint was the proportion of patients who were in remission at both weeks 36 and 48.38 Remission is defined as Birmingham Vasculitis Activity Score (BVAS)=0 and OCS dose less than or equal to 4mg/day.38   

All patients who complete the 52-week double-blind treatment period may be eligible to continue into an open label extension (OLE) period, intended to allow each patient at least one year of treatment with open-label FASENRA.38

Mepolizumab is a humanized IL-5 antagonist monoclonal antibody.39

FASENRA

FASENRA (benralizumab) is a monoclonal antibody that binds directly to IL-5 receptor alpha on eosinophils and attracts natural killer cells to induce rapid and near-complete depletion of eosinophils via apoptosis (programed cell death).40,41 FASENRA is currently approved as an add-on maintenance treatment for severe eosinophilic asthma in the US, EU, Japan and other countries, and is approved for self-administration in the US, EU and other countries.42,43

The FDA granted Orphan Drug Designation for FASENRA for EGPA in 2018 and AstraZeneca continues to explore FASENRA'S potential beyond severe asthma, as a treatment across many diseases where eosinophils are expected to play a role.44-47

FASENRA was developed by AstraZeneca and is in-licensed from BioWa, Inc., a wholly-owned subsidiary of Kyowa Kirin Co., Ltd., Japan.

AstraZeneca in Respiratory and 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.