GSK announced today that the European Commission has approved a new subcutaneous (SC) formulation of Benlysta (belimumab), as an add-on therapy in adult patients with active autoantibody-positive systemic lupus erythematosus(SLE) with a high degree of disease activity (e.g. positive anti-dsDNA and low complement) despite standard therapy. SLE is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time, affecting almost any system in the body.
The approval is for a single-dose prefilled syringe and a single-dose prefilled pen (autoinjector) presentation, administered as a once weekly injection of 200mg. These SC presentations enable patients to self-administer their medicine at home, after initial supervision from their clinical team if considered appropriate. The subcutaneous version of the medicine adds to the existing intravenous (IV) formulation, which was licensed for use in Europe in 2011 and has since been used to treat thousands of patients worldwide.
Vlad Hogenhuis, Senior Vice President, Head of Specialty Care, GSK said, “We are delighted to receive today’s European approval. The impact of living with lupus forces individuals to adapt their daily personal and working lives in order to manage this complex, chronic disease. With the availability of the IV and subcutaneous formulations of Benlysta, we can now offer patients with SLE and their physicians additional choice, enabling either home or hospital administration of the medicine”.
The approval is based on results from the BLISS-SC phase III pivotal study of more than 800 patients with active SLE, published earlier this year in Arthritis & Rheumatology. The study measured reduction in disease activity at Week 52 in patients receiving Benlysta plus standard of care, versus those receiving placebo plus standard of care (assessed by SRI, a composite measure of efficacy in lupus).
The Benlysta subcutaneous formulation was approved for use in the US in July 2017 and Japan in September 2017 and further regulatory submissions are under review or planned in other countries.
The Benlysta intravenous formulation is licensed for use in over 70 countries worldwide, including the US, Japan and EU countries. It is administered by healthcare professionals to patients as a weight-based dose of 10mg/kg, via a one-hour infusion in a hospital or clinical setting every four weeks (following an initial loading phase given at Weeks 0, 2 and 4).
About Benlysta (belimumab)
Benlysta is currently the only medicine specifically developed and approved for SLE. Benlysta, a BLyS-specific inhibitor, is a human monoclonal antibody that binds to soluble BLyS. Benlysta does not bind B cells directly. By binding BLyS, Benlysta inhibits the survival of B cells, including autoreactive B cells, and reduces the differentiation of B cells into immunoglobulin-producing plasma cells.
Benlysta is available as 120 mg in a 5-mL single-use vial and 400 mg in a 20-mL single-use vial for injection, for intravenous use. Benlysta is available as a 200mg single-dose autoinjector for subcutaneous injection.
Benlysta is licensed in the European Union as an add-on therapy in adult patients with active autoantibody-positive SLE, with a high degree of disease activity (e.g. positive anti-dsDNA and low complement), despite standard therapy.
For the EU Summary of Product Characteristics for Benlysta, please visit www.ema.europa.eu
Benlysta is licensed in the US for the treatment of adult patients with active, autoantibody-positive, systemic lupus erythematosus (SLE) who are receiving standard therapy: Limitations of Use: The efficacy of Benlysta has not been evaluated in patients with severe active lupus nephritis or severe active central nervous system lupus. Benlysta has not been studied in combination with other biologics or intravenous cyclophosphamide. Use of Benlysta is not recommended in these situations.
Full US prescribing information including Medication Guide is available at: https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Benlysta/pdf/BENLYSTA-PI-MG.PDF
About systemic lupus erythematosus (SLE)
Systemic lupus erythematosus (SLE) is the most common form of lupus, affecting approximately 70 percent of an estimated 5 million people with lupus worldwide. SLE is a chronic, incurable, autoimmune disease associated with a range of symptoms that can fluctuate over time including painful or swollen joints, extreme fatigue, unexplained fever, skin rashes and organ damage.
Important Safety Information for belimumab
The following safety information is based on a summary of the European Summary of Product Characteristics for Benlysta. Please consult the full Summary of Product Characteristics for all the labelled safety information for Benlysta (belimumab).
Hypersensitivity to belimumab or any excipients.
Warnings and precautions:
Not recommended in patients with severe active central nervous system lupus, severe active lupus nephritis, HIV, history of/current hepatitis B or C, hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl) and patients with a history of major organ transplant or hematopoietic stem/cell/marrow transplant or renal transplant.
Concomitant use with B cell targeted therapy or cyclophosphamide: Caution in patients receiving other B cell targeted therapy or cyclophosphamide.
Malignancies and lymphoproliferative disorders: Caution in patients with a history of malignancy or who develop malignancy whilst receiving treatment.
Infusion reactions and hypersensitivity: Administration may result in hypersensitivity reactions and infusion reactions which can be severe, and fatal. In the event of a severe reaction, administration must be interrupted and appropriate medical therapy administered. Risk of hypersensitivity reactions is greatest with the first two infusions; however the risk should be considered for every infusion.
Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Premedication including an antihistamine, with or without antipyretic, may be administered before infusion of Benlysta. There is insufficient knowledge to determine whether premedication could diminish the frequency or severity of infusion reactions. Patients have been reported to develop symptoms of acute hypersensitivity several hours after the infusion has been administered.
Recurrence of clinically significant reactions after initial appropriate treatment of symptoms has also been observed. Therefore, Benlysta should be administered in an environment where resources for managing such reactions are immediately available. Patients should remain under clinical supervision for a prolonged period of time (for several hours), following at least the first 2 infusions, taking into account the possibility of a late onset reaction. Patients should be advised that hypersensitivity reactions are possible on the day of, or the day after infusion, and be informed of potential signs and symptoms and the possibility of recurrence. Patients should be instructed to seek immediate medical attention if they experience any of these symptoms. The package leaflet should be provided to the patient each time Benlysta is administered. Delayed-type, non-acute hypersensitivity reactions have also been observed and included symptoms such as rash, nausea, fatigue, myalgia, headache, and facial oedema.
Infections: The mechanism of action of Benlysta could increase the potential risk of infections, including opportunistic infections and may interfere with the response to immunisations. Severe infections, including fatal cases, have been reported in SLE patients receiving belimumab. Exercise caution when considering use in patients with chronic infections or a history of recurrent infection. Do not use in patients receiving therapy for chronic infection. Patients who develop an infection while undergoing treatment with Benlysta should be monitored closely and careful consideration given to interrupting therapy until the infection is resolved.
Progressive multifocal leukoencephalopathy: There have been reports of progressive multifocal leukoencephalopathy (PML). Be alert to symptoms that patients may not notice e.g cognitive, neurological or psychiatric symptoms or signs. Monitor for any new or worsening symptoms or signs and if these occur, refer to a neurologist. Suspend further dosing if PML is suspected until it is excluded.
Immunisation: Live vaccines should not be given for 30 days before, or concurrently with Benlysta
Pregnancy and lactation:
Limited data on use in pregnant women. Not to be used unless clearly necessary. Not known whether Benlysta is excreted in human milk or absorbed after ingestion. Maternal IgG is secreted in breast milk so recommended to either discontinue Benlysta or breast feeding.
Very common: Bacterial infections (e.g. bronchitis, urinary tract infections), diarrhoea, nausea. Common: Gastroenteritis viral, pharyngitis, nasopharyngitis, viral upper respiratory tract infection, leucopenia, hypersensitivity reactions, depression, migraine, injection site reactions, pain in extremity, infusion or injection-related systemic reactions, pyrexia. Uncommon: Anaphylactic reaction, angioedema, urticaria, rash. Rare: Delayed-type, non-acute hypersensitivity reactions. See Summary of Product Characteristics for full details.
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Cautionary statement regarding forward-looking statements
GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D ‘Principal risks and uncertainties’ in the company’s Annual Report on Form 20-F for 2016.