Systemic Lupus Erythematosus is a chronic inflammatory disease that affects connective tissues such as cartilage and blood vessel lining, which provide strength and flexibility to body structures. Systemic Lupus Erythematosus affects multiple organs and structures, including the skin, joints, kidneys, lungs, central nervous system, and blood-forming (hematopoietic) system, and the signs and symptoms vary between individuals. The exact cause of SLE is unknown; however, factors such as sunlight and drugs may precipitate the condition, and many studies have revealed a complex genetic basis. The risk factors for SLE include the medicines that induce lupus, age, race/ethnicity, and family history.
The severity of lupus flares ranges from moderate to severe. SLE is most common in women of reproductive age (often beginning at childbearing age), but lupus is becoming more common after 40, particularly among Europeans. As per DelveInsight estimates, the diagnosed prevalent cases of SLE were found to be 651,965 in the 7MM in 2020, with the USA accounting for the maximum prevalence. Moreover, the epidemiological analysis estimated that mild SLE cases were higher, followed by moderate SLE prevalent cases, with severe SLE accounting for the least number of SLE prevalent cases.
Systemic Lupus Erythematosus Treatment Landscape
The Systemic Lupus Erythematosus treatment is mainly based on the first-line and second-line of therapy. The first line of therapy/agents recommended for the Systemic Lupus Erythematosus treatment includes Nonsteroidal anti-inflammatory drugs (NSAIDs) (Naproxen, Celecoxib, etc.), Glucocorticoids, Antimalarial agents.
The second line of therapy/treatment recommended for Systemic Lupus Erythematosus treatment includes Intravenous Immunoglobulin (methotrexate, azathioprine, or mycophenolate), Targeted immunotherapy, Cytotoxic, and Immunosuppressive therapies (Lupkynis, Methotrexate, Azathioprine, Cyclophosphamide, Mycophenolate mofetil).
Hydroxychloroquine and BENLYSTA are the FDA-approved therapies for SLE treatment. With the approval of these therapies, the outlook for SLE patients improved from a 4-year survival rate of ~50% in 1950 to a 15-year survival rate of ~85% by 2013.
Hydroxychloroquine was first recommended for its use against malaria in 1955, but a year later it got the FDA approval to treat autoimmune disorders such as SLE and Rheumatoid Arthritis. During the coronavirus outbreak, it came into the limelight as a treatment option for Covid-19. It belongs to the class of drugs known as disease-modifying antirheumatic drugs (DMARDs). It is sold under the brand name Plaquenil and is available only by prescription. It is also available as a generic medicine. On the other hand, BENLYSTA has completely changed the SLE treatment landscape as it has been used in treating SLE patients for over a decade now.
BENLYSTA (Belimumab): First Targeted Biological Treatment for SLE
BENLYSTA is a biologic therapy that is given intravenously (IV) or subcutaneously to adults who have active Systemic Lupus Erythematosus (SLE or lupus) or active Lupus Nephritis and are taking other lupus medications. BENLYSTA (Belimumab) is developed by the pharma giant GlaxoSmithKline (GSK) and it is the first and only FDA-approved therapy for both lupus and lupus nephritis.
BENLYSTA was first approved as an Intravenous (IV) formulation in the United States and EU for SLE back in 2011 and thus making it the first-ever targeted biological treatment for SLE patients. After six years, in 2017, it was approved as a subcutaneous formulation for SLE in the United States and EU, and in the same year, it was approved as both Intravenous (IV) and subcutaneous formulation in Japan. In 2019, Belimumab became the first-ever treatment option for pediatric patients with lupus in the United States. Last year, it was approved for Lupus Nephritis in the United States. It was also recommended for adult patients with active lupus nephritis by the EMA committee. The patent expiration of BENLYSTA (Belimumab) is approaching fast. The patent will expire in the United States and Europe in 2025 and 2026, respectively.
Benlysta Sales and Annual cost of therapy (ACOT)
BENLYSTA (Belimumab) is a blockbuster drug of GSK used to treat Systemic Lupus Erythematosus and Lupus Nephritis. As per DelveInsight’s report on Benlysta (Belimumab) market forecast, the sale of Belimumab has kept on increasing year after year. In 2017, the total sale of Belimumab was USD 119 million across all three regions (the United States, Europe, and International). In 2018, it generated a whopping revenue of USD 657 million, more than five times the last year’s sales across all three regions. Since then, it came out as a blockbuster drug, owing to the launch of the subcutaneous version of BENYLSTA. It is the major contributor to this increase in sales. The maximum sale of Belimumab was observed in the United States. The drug generated USD 578 million through its sales in the US. The same was observed in 2019 and 2020. The maximum revenue generated by the drug was in the US region, i.e., USD 706 million and USD 782.5 million in 2019 and 2020, respectively. While the total revenue generated through its sales across all the regions in 2019 and 2020 was USD 809 million and USD 919.5 million, respectively. As per DelveInsight analysis, this blockbuster drug is expected to generate more than 1 billion in 2022, while the peak sale estimate of Belimumab is around USD 1.3-1.4 billion.
BENLYSTA (Belimumab) is available in two options for individuals with Lupus and Lupus Nephritis- Intravenously and Subcutaneously. The Belimumab amount recommended for the solution for SC injections is 200 mg/mL, while the recommended amount for lyophilized powder for IV infusion is 120mg/5mL and 400mg/20mL single-use vials. The average annual drug cost is USD 45,000 per year.
Systemic Lupus Erythematosus Pipeline Overview
There are several SLE therapies in the pipeline that are under investigation in different phases of clinical trials for the treatment of Systemic Lupus Erythematosus. Several pharmaceutical companies including AstraZeneca, Biogen, Roche, and others are evaluating their drug candidates with novel MoA that can be used as first-line or second-line therapy to treat SLE and are expected to join the market in the upcoming years.
|Drug||Molecule||Phase||Company||MoA||LOT||Expected Launch Year|
|Anifrolumab||Monoclonal antibody||–||AstraZeneca||Type I IFN receptor blocker||First-line||Approved|
|Dapirolizumab pegol||Fab antibody||Phase III||UCB Pharma/Biogen||CD40 ligand (CD40L) blocker||Second-line||2024|
|Baricitinib||Small molecule||Phase III||Eli Lilly and Company/Incyte Corporation||JAK1 and JAK2 Inhibitor||Second-line||2023|
|Lupuzor (forigerimod)||Peptide||Phase III||ImmuPharma||Auto-reactive T-cells activation and immune cascade modulator||Second-line||2022|
|Gazvya (Obinutuzumab)||Monoclonal antibody||Phase II||Roche||Type I anti-CD20 antibodies||Second-line||2026|
Market Potential of the Upcoming Systemic Lupus Erythematosus Therapies
As per DelveInsight analysis, the SLE market size was USD 1,462.5 million in the 7MM in 2020, which is expected to increase by 2030 owing to the launch of emerging therapies. Currently, the SLE therapeutics market revolves around only one drug, i.e., Belimumab. It is the top-selling medication in the market. Several pharmaceutical companies such as AstraZeneca, Eli Lilly and Company, Incyte Corporation, ImmuPharma, and others are now gearing up to compete with this drug by launching their lead assets into the market.
Saphnelo (anifrolumab-fnia) (formerly MEDI-546), developed by AstraZeneca, is a first-in-class type I interferon (IFN) receptor antagonist approved for the treatment of adult patients with moderate to severe Systemic Lupus Erythematosus (SLE). Anifrolumab produced a significant response when compared to placebo in the TULIP-1 and TULIP-2 trials. Additionally, the drug reduced overall disease activity reduced corticosteroid use and improved skin manifestations. The FDA approved the drug for the treatment of adults with moderate to severe SLE who are receiving standard of care treatment in August 2021. Saphnelo is also being evaluated for SLE in the European Union and Japan. It is the only new therapy in over a decade for patients with Systemic Lupus Erythematosus. As per the DelveInsight forecast analysis, the market size of Anifrolumab is estimated to be approximately USD 1000-1100 million in 2028. According to the analyst report, Anifrolumab can become the blockbuster drug by 2030 and give strong competition to GlaxoSmithKline’s Benlysta. The drug is also in development for other indications such as Lupus nephritis, Rheumatoid arthritis.
Baricitinib, also known as LY3009104 or INCB028050, is a novel orally bioavailable inhibitor of the tyrosine-protein kinase JAK1 or JAK2. It is being developed and investigated in Phase III studies by Eli Lilly and Company in collaboration with Incyte Corporation for Systemic Lupus Erythematosus treatment. According to the findings of the study, 67 percent of patients in the 4-mg group achieved the SLE Disease Activity Index-2K response, compared to 53 percent in the placebo group. As per the DelveInsight sales forecast, the market size of Baricitinib for the year 2028 is expected to be between USD 700-750 million. Baricitinib got the approval for Rheumatoid Arthritis in Japan and EU in 2017, and in 2018 it was approved for the same in the United States. It is in development for other indications such as Atopic Dermatitis, Alopecia Areata, Juvenile Idiopathic Arthritis, Psoriasis, Diabetic Kidney Disease, Aicardi Goutieres Syndrome, Uveitis, Polymyalgia Rheumatic (PMR), Idiopathic Inflammatory Myopathies.
Lupuzor (Forigerimod / IPP-201101)
Lupuzor, a potential treatment for Lupus, is ImmuPharma’s flagship drug. Lupuzo is a medication that specifically modulates the immune system of lupus patients by changing the behavior of some of the essential cells involved in the disease’s pathogenesis. The unique mechanism of action of Lupuzor consists in modulating the activation of auto-reactive T-cells. Other attempts to modulate the immune response in SLE, with little success to date, have been made further downstream in the immune cascade, most notably in B-cell regulation. Lupuzor, on the other hand, presents a novel approach to modulating this unwanted autoimmunity by targeting upstream T-cell activation. Previous data showed statistically significant reductions in disease activity (71.1 percent versus 48.8 percent) compared to placebo plus standard of care (“comparator group”) in 79 patients (60.8 percent) who were anti-dsDNA autoantibody-positive (“Antibody Positive”). The US FDA has granted it ‘Gold Standard’ approval for its Phase III program, including a Special Protocol Assessment (SPA) and fast track designation. As per DelveInsight forecast analysis, Lupuzor is expected to gain a USD 950-1000 million market size in 2028.
There are numerous aspects of SLE disease pathogenesis and clinical outcomes that remain unknown. Because of the disease’s unexplained aspects, management of the disease remains a clinical challenge for the scientific community. Another challenge for treating SLE patients is the lack of approved therapies. There is a significant unmet medical need for effective treatments with a favorable safety profile for improved clinical outcomes.