AstraZeneca Pharmaceuticals LP

03/21/2024 | Press release | Distributed by Public on 03/21/2024 13:42

SAPHNELO® demonstrates higher rates of remission in patients with systemic lupus erythematosus compared to standard therapy alone over 4-year period

PUBLISHED21 March 2024

AstraZeneca presents new post-hoc analysis from Phase III TULIP long-term extension trial at the European Lupus Meeting 2024

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

These data will be presented today at the 14th European Lupus Meeting of the European Lupus Society, in Bruges, Belgium.

In this new post-hoc analysis of the TULIP long-term extension (LTE) trial, a numerically greater number of patients treated withSAPHNELO achieved remission vs. those treated with standard therapy alone. At the end of the four-year TULIP program (Week 208), 30.3% (n=58/194) of patients treated withSAPHNELO were in remission compared with 18.3% (n=12/65) of those in the standard therapy alone group. This was an increase from 19.7% (n=49/251) of patients treated with SAPHNELO who achieved remission at the first LTE visit (Week 64) compared with 9.9% (n=10/104) of those in the standard therapy alone group.1,2 SAPHNELO is the first biologic with remission data in SLE from a four-year placebo-controlled trial.

In this new analysis, remission was defined using the DORIS criteria (Definition of Remission in SLE): total clinical SLEDAI-2K, or "Systemic Lupus Erythematosus Disease Activity Index 2000" score of 0 (sum of all SLEDAI-2K items except increased DNA binding and low complement), physician global assessment <0.5, oral corticosteroid (OCS) dose of ≤5 mg per day, stable maintenance doses of immunosuppressants, no use of restricted medicines, and no premature discontinuation of SAPHNELO, as well as clinical labs.1

An initial analysis of the TULIP-LTE trial presented at ACR Convergence 2023 calculated clinical SLEDAI-2K excluding all laboratory measures. Results were similar when all laboratory parameters or only serology parameters were excluded.3

SLE is a serious and complex autoimmune condition that can affect any organ, and patients often experience inadequate disease control.4,5 In lupus, remission is associated with reduced organ damage, fewer flares, reduced hospitalization, reduced mortality and improved health-related quality of life.6,7

Ronald van Vollenhoven, Chair of Rheumatology and Director of the Amsterdam Rheumatology & Immunology 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. With anifrolumab, we now have a strong body of evidence that shows sustained remission can be achieved, representing a real step forward for SLE treatment."

Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "These data add to our understanding of SAPHNELO'scompelling 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 sustained long-term 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."

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.8

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

Systemic lupus erythematosus

SLE is an autoimmune disease in which the immune system attacks healthy tissue in the body.5 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.9 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.5,10

Phase III TULIP clinical program

All three TULIP trials for SAPHNELO(TULIP-1, TULIP-2, and TULIP-LTE) were randomized, double-blinded, placebo-controlled trials in patients with moderate-to-severe SLE who were receiving standard therapy.11-13 The placebo arm of the trial included at least one of the following standard therapies: OCS, antimalarials and immunosuppressants (methotrexate, azathioprine or mycophenolate mofetil).14-16

The longest placebo-controlled clinical trial performed in SLE to date,17 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.13 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 analyzed for the 4-year TULIP+LTE period.

SAPHNELO

SAPHNELO (anifrolumab) is a first-in-class, fully human monoclonal antibody that binds to subunit 1 of the type I interferon (IFN) receptor, blocking the activity of type I IFN.18,19 Type I IFNs, such as IFN-alpha, IFN-beta and IFN-kappa, are cytokines involved in regulating the inflammatory pathways implicated in SLE.20-25 The majority of adults with SLE have increased type I IFN signaling, which is associated with increased disease activity and severity.20,26

SAPHNELOis approved to treat SLE in more than 60 countries worldwide including the US, EU and Japan, with reviews ongoing in other countries.3 SAPHNELO continues to be evaluated in the TULIP-SC Phase III trial assessing subcutaneous delivery in SLE,27 the AZALEA Phase III trial in SLE in China,28 and the IRIS Phase III trial in lupus nephritis.29 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.30,31

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.

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. Please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

Contacts

Brendan McEvoy +1 302 885 2677
Jillian Gonzales +1 302 885 2677

US Media Mailbox: [email protected]

###

References

  1. 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).
  2. AstraZeneca Data on file. 2024. REF-216754.
  3. AstraZeneca.com. Saphnelo data show patients more likely to achieve and sustain remission in systemic lupus erythematosus compared to standard therapy alone. Available at: Saphnelo data show patients more likely to achieve and sustain remission in systemic lupus erythematosus compared to standard therapy alone (astrazeneca.com) [Last accessed: March 2024].
  4. Medscape. Systemic Lupus Erythematosus (SLE). Available at: https://emedicine.medscape.com/article/332244-overview [Last accessed: March 2024].
  5. Bruce IN, et al. Factors associated with damage accrual in patients with systemic lupus erythematosus: results from the systemic lupus international collaborating Clinics (SLICC) inception cohort. Ann Rheum Dis. 2015;74:1706-1713.
  6. Ugarte-Gil MF, et al. Achieving remission or low disease activity is associated with better outcomes in patients with systemic lupus erythematosus: a systematic literature review. Lupus Sci Med. 2021;8:e000542. doi:10.1136/lupus-2021-000542.
  7. Kandane-Rathnayake R, et al. Lupus low disease activity state and remission and risk of mortality in patients with systemic lupus erythematosus: a prospective, multinational, longitudinal cohort study. Lancet Rheumatol. 2022;4(12):e822-e830.
  8. Fanouriakis A, et al. EULAR recommendations for the management of systemic lupus erythematosus: 2023 update. Ann Rheum Dis. 2024;83:15-29.
  9. American College of Rheumatology. Guidelines for referral and management of systemic lupus erythematosus in adults. Arthritis & Rheumatology. 1999;42:1785-1796. 
  10. Segura BT, et al. Damage accrual and mortality over long-term follow-up in 300 patients with systemic lupus erythematosus in a multi-ethnic British cohort. Rheumatol. 2020;59(3):524-533. 
  11. 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?term=NCT02446912&rank=1 [Last accessed: March 2024].
  12. 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: March 2024].
  13. 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: March 2024].
  14. Furie R, et al. Type I interferon inhibitor anifrolumab in active systemic lupus erythematosus (TULIP-1): a randomised, controlled, phase 3 trial. Lancet Rheumatol. 2019;1(4):e208-e219.
  15. Morand EF, et al. Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 2020;382(3):211-221.
  16. AstraZeneca Clinical Study Protocol. A Multicentre, Randomised, Double-blind, Placebo-Controlled Phase 3 Extension Study to Characterise the Long-term Safety and Tolerability of Anifrolumab in Adult Subjects with Active Systemic Lupus Erythematosus. Available at: https://storage.googleapis.com/ctgov2-large-docs/85/NCT02794285/Prot_000.pdf [Last accessed: March 2024].
  17. Kalunian KC, et al. A Randomized, Placebo-Controlled Phase III Extension Trial of the Long-Term Safety and Tolerability of Anifrolumab in Active Systemic Lupus Erythematosus. Arthritis Rheumatol. 2023;75(2):253-265. doi:10.1002/art.42392.
  18. Riggs JM, et al. Characterisation of anifrolumab, a fully human anti-interferon receptor antagonist antibody for the treatment of systemic lupus erythematosus. Lupus Sci Med. 2018;5(1):e000261.
  19. Furie R, et al. Anifrolumab, an Anti-Interferon‐α Receptor Monoclonal Antibody, in Moderate‐to‐Severe Systemic Lupus Erythematosus. Arthritis Rheumatol. 2017;69(2):376-386.
  20. Lauwerys BR, et al. Type I interferon blockade in systemic lupus erythematosus: where do we stand? Rheumatol. 2014;53:1369-1376.
  21. 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.
  22. Jefferies CA. Regulating IRFs in IFN Driven Disease. Front Immunol. 2019;10:325.
  23. 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.
  24. 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.
  25. Rönnblom L, et al. Interferon pathway in SLE: one key to unlocking the mystery of the disease. Lupus Sci Med. 2019;6(1):e000270.
  26. Crow MK. Type I Interferon in the Pathogenesis of Lupus. J Immunol. 2014;192(12):5459-5468.
  27. ClinicalTrials.gov. Subcutaneous Anifrolumab in Adult Patients With Systemic Lupus Erythematosus (Tulip SC). Available at: https://clinicaltrials.gov/study/NCT04877691 [Last accessed: March 2024].
  28. ClinicalTrials.gov. Anifrolumab Asian PhIII Efficacy Study for Systemic Lupus Erythematosus (SLE). Available at: https://clinicaltrials.gov/study/NCT04931563 [Last accessed: March 2024].
  29. ClinicalTrials.gov. Phase 3 Study of Anifrolumab in Adult Patients With Active Proliferative Lupus Nephritis (IRIS). Available at: https://clinicaltrials.gov/study/NCT05138133 [Last accessed: March 2024].
  30. AstraZeneca.com. First patients dosed in IRIS Phase III trial evaluating Saphnelo in lupus nephritis. Available at: https://www.astrazeneca.com/media-centre/medical-releases/first-patients-dosed-in-iris-phase-iii-trial-evaluating-saphnelo-in-lupus-nephritis.html [Last accessed: March 2024].
  31. AstraZeneca.com. Determine effectiveness of Anifrolumab In SYstemic sclerosis (DAISY) - DAISY. Available at: https://www.astrazenecaclinicaltrials.com/study/D3460C00002/ [Last accessed: March 2024].