Positive full results from the Phase III TULIP-SC trial showed the subcutaneous (SC) administration of Saphnelo (anifrolumab) demonstrated a statistically significant and clinically meaningful reduction in disease activity compared to placebo in patients with systemic lupus erythematosus (SLE).1 The results were published in Arthritis & Rheumatology.
In the TULIP-SC full analysis, 56.2% of patients who received Saphnelo achieved a reduction in disease activity at Week 52 versus 37.1% receiving placebo, as measured by the British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) (difference [95% CI]=19.1% [9.0-29.2%]; p=0.0002), which was consistent with results from previous trials.1-4 The safety profile observed in the TULIP-SC trial was consistent with the known clinical profile of Saphnelo administered as an intravenous (IV) infusion.1-4 The full results confirmed the findings from the interim analysis, which was statistically significant.1
Patients with SLE have a higher risk of early death and an estimated 50% have irreversible organ damage within five years of diagnosis due to disease activity and chronic oral corticosteroid (OCS) use.5,6 Lowering disease activity while reducing OCS use reduces the risk of long-term organ damage and helps patients avoid the debilitating effects of the disease.7 Recently revised treatment recommendations for SLE now emphasise DORIS remission attainment as the primary goal of care and strongly encourage tapering toward OCS discontinuation to minimise long-term exposure.8,9
Susan Manzi, MD, MPH, chair of the Allegheny Health Network (AHN) Medicine Institute, director of the Lupus Center of Excellence at the AHN Autoimmunity Institute and principal investigator of the TULIP-SC trial, said: "These meaningful results from the TULIP-SC trial provide confidence that the efficacy and DORIS-defined remission rates that we've seen with anifrolumab can be achieved in a new subcutaneous administration, allowing even more patients to benefit from this effective treatment. The results align with important changes in global lupus treatment recommendations, which now emphasise earlier intervention with biologics, driving remission and reduced use of oral corticosteroids as key treatment goals."
Sharon Barr, Executive Vice President, BioPharmaceuticals R&D, AstraZeneca, said: "These results reinforce Saphnelo's unique approach of targeting the type 1 interferon receptor to reduce disease activity, with the added convenience of subcutaneous self-administration. The TULIP-SC findings build on the compelling body of evidence for Saphnelo, which has helped patients achieve remission and significantly reduce reliance on oral corticosteroids - further reinforcing our ambition to transform lupus care."
In the TULIP-SC trial, Saphnelo demonstrated clinically meaningful effects across a range of outcome measures: reduction in SLE disease activity while tapering to low dose of OCS (≤7.5 mg/day), more patients achieving a BICLA response sooner, and numerically delayed time to first flare.1 In pre-specified secondary and exploratory endpoints, 29.0% of patients taking Saphnelo achieved DORIS remission and 40.1% attained low-level disease activity, as measured by the Low-Level Disease Activity Score (LLDAS).1
Subcutaneous Saphnelo was well tolerated, and the frequency of overall adverse events was balanced between the Saphnelo and placebo treatment groups.1
Saphnelo IV infusion is approved for the treatment of moderate to severe SLE in more than 70 countries worldwide including the US, EU and Japan, with regulatory reviews ongoing in other countries including China. To date, more than 40,000 patients globally have been treated with Saphnelo.10 SC administration of Saphnelo is approved in the EU and is under regulatory review in several countries around the world, including the US and Japan.
Table 1: Summary of secondary endpoints1
Key Secondary Endpoints |
Anifrolumab (120mg) (n=184) |
Placebo (n=183) |
Difference vs. Placebo / Hazard Ratio (95% CI) |
|---|---|---|---|
Key Secondary Endpoints Proportion of BICLA responders able to maintain low or reduced oral corticosteroid doses from Week 40 to Week 52 |
Anifrolumab (120mg) (n=184) 56.2% [103/184] |
Placebo (n=183) 34.0% |
Difference vs. Placebo / Hazard Ratio (95% CI) Difference [95% CI] = 22.3% (12.3-32.2) p<0.0001 |
Key Secondary Endpoints Time to BICLA response sustained through Week 52 |
Anifrolumab (120mg) (n=184) 41.5% [76/184] |
Placebo (n=183) 22.6% |
Difference vs. Placebo / Hazard Ratio (95% CI) HR [95% CI] = 2.2 (1.5-3.2) p<0.0001 |
Key Secondary Endpoints Time to flare over 52 weeks |
Anifrolumab (120mg) (n=184) 40.9% [74/184] |
Placebo (n=183) 48.5% |
Difference vs. Placebo / Hazard Ratio (95% CI) HR [95% CI] = 0.76 (0.55-1.03) p=0.0798 |
Key Secondary Endpoints Pre-specified Secondary and Exploratory Endpoints |
Anifrolumab (120mg) (n=184) Anifrolumab (n=184) |
Placebo (n=183) Placebo (n=183) |
Difference vs. Placebo / Hazard Ratio (95% CI) Difference vs. Placebo (95% CI) |
Key Secondary Endpoints DORIS remission attainment at Week 52 |
Anifrolumab (120mg) (n=184) 29.0% [53/184] |
Placebo (n=183) 14.7% [27/183] |
Difference vs. Placebo / Hazard Ratio (95% CI) Difference [95%CI] = 14.2% (5.6-22.8) nominal p=0.0012* |
Key Secondary Endpoints LLDAS attainment at Week 52 |
Anifrolumab (120mg) (n=184) 40.1% [74/184] |
Placebo (n=183) 26.0% [48/183] |
Difference vs. Placebo / Hazard Ratio (95% CI) Difference [95%CI] = 14.1% (4.6-23.6) nominal p=0.0038* |
*P-values are nominal and not adjusted for multiplicity.
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.11 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.8,9,11,12
Over 3.4 million people globally are affected by SLE.13 It is among the leading causes of death in young women in the US, and is more common amongst Asian, Black or Hispanic populations.14,15 Living with SLE can be painful, debilitating and have a profound impact on patients' mental and financial wellbeing.6,12,16-19
An estimated 50% of people with SLE have irreversible organ damage within five years of diagnosis due to long-term corticosteroid use and disease activity.5,6 Even a small reduction in daily oral corticosteroid use (for example 1mg/day) can lower the risk of organ damage.7
TULIP-SC
TULIP-SC was a Phase III, multicentre, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of a subcutaneous administration of anifrolumab versus placebo in participants aged 18 to 70 years with moderately to severely active, autoantibody-positive SLE, with both treatment groups receiving standard therapy (oral corticosteroids, antimalarial, and/or immunosuppressants).1,20
The reduction of disease activity was measured using the BICLA at week 52.1,20 The BICLA requires improvement in all organs with disease activity at baseline with no new flares.1,20
Participants (367) were randomised 1:1 to receive 120mg subcutaneous dose of anifrolumab or placebo administered via a pre-filled, single-use syringe.1,20 A pre-specified interim analysis was conducted when the first 220 participants reached week 52.1,20 The trial also includes an open-label extension period of 52 weeks for participants who completed the 52-week treatment period.1,20
The primary endpoint in the trial was the proportion of patients who attained a BICLA response at Week 52.1,20
In the interim analysis, once-weekly subcutaneous administration of Saphnelo significantly reduced SLE disease activity with 59.4% of patients who received Saphnelo achieving a BICLA response versus 43.9% receiving placebo at Week 52 ([95% CI] = 15.5% [2.3-28.6%]; p=0.0211).1
Saphnelo subcutaneous administration
Subcutaneous administration of Saphnelo was approved in the EU in December 2025. Since 2021, Saphnelo has been available in an IV infusion administered by healthcare professionals in a hospital or clinic setting. Subcutaneous administration offers patients the choice to self-administer treatment outside of the clinic and or with support from an HCP or caregiver via a simple process.
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.2,21 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
Saphnelo IV is the first biologic with remission data in SLE from a four-year placebo-controlled Phase III trial (TULIP-LTE) and was measured with the DORIS criteria for remission.28,29 DORIS is measured as clinical SLEDAI-2K, or "Systemic Lupus Erythematosus Disease Activity Index 2000" score of 0, physician global assessment <0.5, prednisolone/ equivalent dose of OCS dose of ≤5 mg per day and stable maintenance doses of immunosuppressants, including biologics.30
Saphnelo continues to be evaluated in diseases where type I IFN plays a key role, including Phase III trials in cutaneous lupus erythematosus, myositis, systemic sclerosis and lupus nephritis.31-34
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.
