AstraZeneca's Saphnelo (Anifrolumab): First-in-Class Type I Interferon Receptor Antagonist Approved in the EU for Moderate to Severe Systemic Lupus Erythematosus

News on February 16, 2022 /BioValleyBIOON/ --AstraZenecaAstraZeneca recently announced,Monoclonal Antibody DrugsSaphnelo (anifrolumab) has been approved in the EU: as an add-on therapy for the treatment of moderate to severe, active, autoantibody-positive systemicSystemic Lupus Erythematosus(SLE) adult patients. In the United States, Saphnelo was approved in August 2021 for the treatment of moderate to severe SLE adult patients receiving standard therapy.

Saphnelos is the first new therapy for SLE approved in the U.S. and EU in over a decade, and it is also the only biologic agent indicated for SLE patients regardless of high disease activity.Saphnelo is a first-in-class Type I interferon receptor (IFNAR) antibody.Type I IFN plays a central role in the pathophysiology of lupus, and the increase in Type I IFN signaling is associated with increased disease activity and severity.

SLE is the most common type of lupus, with approximately 300,000 patients in the United States and about 250,000 patients in Europe, most of whom are women diagnosed between the ages of 15 and 45. The disease is complex.AutoimmuneDisease can affect any organ, and patients often experience inadequate disease control, long-term organ damage, and a poor health-related quality of life. In March 2011,GSKBenlysta (Chinese trade name: 倍力腾, generic name: belimumab, Belimumab) was approved by the United StatesFDAApproved, becoming the first treatment for SLE in nearly 60 years after hydroxychloroquine was approved in 1955. In the EU, Benlysta was approved in July 2011.

The active pharmaceutical ingredient of Saphnelo is anifrolumab.This is a fully human monoclonal antibody that binds to the type I interferon receptor subunit 1, blocking the activity of all type I interferons, including IFNα, IFNβ, and IFN-ω.Type I interferons are cytokines involved in inflammatory pathways. A type I interferon gene signature, which has been shown to correlate with disease activity, is elevated in 60%-80% of adult SLE patients. Clinical data indicate that treatment with Saphnelo significantly reduced disease activity in SLE patients by targeting the type I interferon receptor.

This approval is based on the efficacy and safety data from the Saphnelo clinical development program, including two TULIP Phase 3 trials and one MUSE Phase 2 trial. The results of the TULIP-2 trial were published in the *New England Journal of Medicine* in January 2020, the results of the TULIP-1 trial were published in *The Lancet Rheumatology* in December 2019, and the results of the MUSE trial were published in *Arthritis & Rheumatology* in November 2016.

In these trials, patients all received standard treatment,Compared with the placebo group, a higher proportion of patients in the Saphnelo treatment group experienced a reduction in disease activity across entire organ systems, including skin and joints, and achieved a sustained reduction in oral corticosteroid (OCS) use.In these three itemsClinical TrialIn China, patients receiving Saphnelo treatment more commonly experiencedAdverse ReactionsIncluding rhinitis, upper respiratory tract infection, bronchitis, infusion-related reactions, herpes zoster, and cough.

The treatment goal of SLE is to reduce disease activity, prevent damage to organs caused by the disease itself or medications, especially corticosteroids, in order to improve quality of life. Saphnelo will offer the lupus community an effective new treatment option, significantly improving overall disease activity while reducing the use of corticosteroids. This groundbreaking medication has the potential to meaningfully improve the lives of patients with SLE.

Currently, the Phase 3 trial for the Saphnelo subcutaneous formulation in treating SLE has been initiated. AstraZeneca also plans to conduct multiple Phase 3 studies to evaluate Saphnelo in treating lupus nephritis and cutaneous manifestations.Systemic Lupus ErythematosusAnd myositis.

SLE is a chronicAutoimmuneSexually transmitted diseases, where the immune system attacks the body's healthy tissues, can lead to a series of symptoms if left uncontrolled, including pain, rashes, fatigue, joint swelling, fever, long-term organ damage, and even premature death. The disease also has a significant impact on patients' physical and mental health. It is estimated that there are approximately 5 million lupus patients worldwide, with traditional treatments including steroids and immunosuppressants.

In 2011,GSKBenlysta (Belimumab), Approved in the U.S. and EU for Treating Autoantibody-Positive SLE Adult Patients, Becomes the First New Drug for SLE Treatment in Nearly 60 Years. In December 2020 and May 2021, Benlysta was approved in the U.S. and EU respectively for treating Lupus Nephritis (LN). With the approval of this new indication for LN, Benlysta has become the first and only biologic to be approved for both SLE and LN treatment.

Saphnelo has a different mechanism of action compared to Benlysta, which is the first specific inhibitor of B lymphocyte stimulator (BLyS). It blocks the binding of soluble BLyS (a B-cell survival factor) to the BLyS receptor on B cells. Benlysta does not directly bind to B cells but by binding to BLyS, it inhibits the survival of B cells (including autoreactive B cells) and reduces their differentiation into immunoglobulin-producing plasma cells. Benlysta can reduce the number of abnormal B lymphocytes that exacerbate the condition of lupus patients. These abnormal B lymphocytes cause the immune system to mistakenly attack blood vessels and other healthy tissues in the body, leading to lupus and other autoimmune diseases.

In China, Benlysta (trade name: Belimumab) received marketing approval from the NMPA in July 2019. As the world's first biologic approved for the treatment of SLE, Belimumab has been approved in China for use in combination with standard therapy for adult patients with active, autoantibody-positive SLE who have high disease activity despite standard therapy. Belimumab is a fully human monoclonal antibody administered intravenously, inhibiting B-cell proliferation and differentiation, and inducing the apoptosis of autoreactive B cells.Apoptosis, thereby reducing autoantibodies in the serum and achieving the purpose of treating SLE.

It is worth mentioning that, in March 2021, Rongchang Biopharmaceutical announced: the world's first treatment for systemicSystemic Lupus ErythematosusThe "dual-target" novel biologic drug for SLE - Tai'ai (generic name: Telitacicept) has received marketing approval from the National Medical Products Administration, and it is also the first domestically produced dual-target Class I new drug approved for marketing in China in 60 years.

What makes Telitacimab particularly noteworthy is its ability to simultaneously target two key cytokines: BLyS and APRIL. Research has shown that BLyS and APRIL are crucial factors in the abnormal maturation and differentiation of B cells, and the levels of BLyS and APRIL in patients with SLE determine the severity of the disease. By inhibiting BLyS and APRIL, it can completely block the signaling pathway of abnormal B cells, effectively reducing the body's...AutoimmuneResponse, achieving the purpose of treating SLE. (Bioon.com)

Source of the original text:Saphnelo approved in the EU for the treatment of moderate to severe systemic lupus erythematosus