WILMINGTON, Del.--(BUSINESS WIRE)--AstraZeneca’s SAPHNELO™ (anifrolumab-fnia) has been approved in the US for the treatment of adult patients with moderate to severe systemic lupus erythematosus (SLE) who are receiving standard therapy.
The approval by the Food and Drug Administration (FDA) was based on efficacy and safety data from the SAPHNELO clinical development program, including two TULIP Phase III trials and the MUSE Phase II trial. In these trials, more patients treated with SAPHNELO experienced a reduction in overall disease activity across organ systems, including skin and joints, and achieved sustained reduction in oral corticosteroid (OCS) use compared to placebo, with both groups receiving standard therapy.
This marks the first regulatory approval for a type I interferon (type I IFN) receptor antagonist and the only new treatment approved for SLE in more than 10 years. Type I IFN plays a central role in the pathophysiology of lupus and increased type I IFN signaling is associated with increased disease activity and severity.
Dr. Richard Furie, Chief of the Division of Rheumatology at Northwell Health, New York, US and a principal investigator in the SAPHNELO clinical development program, said: “Our treatment goals in systemic lupus erythematosus are to reduce disease activity, prevent organ damage from either the illness itself or the medications, especially steroids, and improve one’s quality of life. Today’s approval of anifrolumab represents a big step forward for the entire lupus community. Physicians will now be able to offer an effective new treatment that has produced significant improvements in overall disease activity, while reducing corticosteroid use.”
Mene Pangalos, Executive Vice President, BioPharmaceuticals R&D, said: “Today’s landmark approval of SAPHNELO is the culmination of years of AstraZeneca’s pioneering research in the type I interferon pathway, a central driver in systemic lupus erythematosus pathophysiology. This ground-breaking medicine has the potential to meaningfully improve the lives of patients living with this often-debilitating disease.”
The adverse reactions that occurred more frequently in patients who received SAPHNELO in the three clinical trials included nasopharyngitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster and cough.
SLE, the most common form of lupus affecting up to 300,000 people in the US, disproportionately affects the African-American, Hispanic and Asian populations. It is a complex autoimmune condition that can affect any organ, and people often experience debilitating symptoms, long-term organ damage and poor health-related quality of life.
Results from the TULIP-2 Phase III trial were published in The New England Journal of Medicine in January 2020, results from the TULIP-1 Phase III trial were published in The Lancet Rheumatology in December 2019 and results from the MUSE Phase II trial were published in Arthritis & Rheumatology in November 2016.
SAPHNELO is under regulatory review for SLE in the EU and Japan. The 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.
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.
IMPORTANT SAFETY INFORMATION
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
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.
Please see full Prescribing Information, including Patient Information.
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 and MUSE
All three trials for SAPHNELO (TULIP-1, TULIP-2 and MUSE) were randomized, double-blinded, placebo-controlled trials in 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 SAPHNELO versus 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 SAPHNELO or placebo every four weeks. TULIP-2 assessed the effect of SAPHNELO in 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 SAPHNELO or 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 SAPHNELO versus placebo. In MUSE, 305 adults were randomized and received a fixed-dose intravenous infusion of 300mg SAPHNELO, 1,000mg SAPHNELO or 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 SAPHNELO in a variety of diseases where type I IFN plays a key role, including lupus nephritis, cutaneous lupus erythematosus and myositis.
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 IFNs. 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.
AstraZeneca is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology 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.
US-53186 Last Updated 7/21