GSK receives positive CHMP opinion for intravenous Benlysta in children with lupus aged five years and above
Issued: London, UK
GSK today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the use of intravenous (IV) Benlysta (belimumab) as an add-on therapy in children aged five years and older with active, autoantibody-positive systemic lupus erythematous (SLE) with a high degree of disease activity.
This opinion for Europe follows the recent approval by the Food and Drug Administration in April 2019 of the IV formulation of Benlysta in the US for children aged five years and above with lupus. A CHMP positive opinion is one of the final steps before a marketing authorisation decision is made by the European Commission.
If approved by the European Commission, children in Europe with lupus who are five years and older, will for the first time have a medicine specifically developed and approved to treat this challenging autoimmune disease.
Data supporting the recommendation
The recommendation is based on data from a post-approval commitment study (the ‘PLUTO’ study), assessing the efficacy, safety and pharmacokinetics of 10 mg/kg IV belimumab plus standard therapy compared with placebo plus standard therapy for one-year in 93 children aged 5 – 11 years (n=13,) and 12 – 17 years (n=80) with SLE. Patients had active SLE disease, defined as a Safety of Estrogens in Lupus Erythematosus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) score ≥6 and positive autoantibodies at screening. As paediatric lupus is an uncommon disease, a fully powered study was not feasible.
The proportion of children achieving a clinically meaningful improvement in disease activity, as assessed by the SLE responder index (SRI) response rate, was numerically higher in patients receiving belimumab plus standard therapy (52.8%) compared with placebo plus standard therapy (43.6%) at Week 52.
The proportion of patients experiencing more than one adverse event (AE) and a serious AE was 79.2% and 17.0% for the belimumab group compared to 82.5% and 35.0% for the placebo group, respectively. No new safety signals were observed in the paediatric population 12 years of age and above (n=80). Safety data in children younger than 12 years of age (n=13) are limited.
About systemic lupus erythematosus (SLE)
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. SLE is the most common form of lupus, affecting approximately 70 percent of an estimated 5 million people with lupus worldwide.
Compared with adult SLE, children with SLE often have more active disease both at the time of diagnosis and over time. SLE in children is associated with more rapid accrual of damage and a higher degree of morbidity compared with SLE in adult populations.[3,4] It is estimated that there are between 3,000 and 6,000 children aged 5-17 years old with SLE in the European Union.
About Benlysta (belimumab)
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 currently the only medicine specifically developed and approved for SLE for adults in Europe. It was approved as an IV formulation in July 2011, and as a subcutaneous (SC) formulation in November 2017.
Benlysta is indicated in the European Union 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.
For the EU Summary of Product Characteristics for Benlysta, please visit www.ema.europa.eu
The IV formulation of Benlysta was recently approved in the US in April 2019 for children with lupus from as young as five years of age. Regulatory submissions are ongoing in other parts of the world.
Benlysta is indicated in the US for the treatment of patients aged 5 years and older 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
The SC formulation of Benlysta is not approved for use in children anywhere in the world.
GSK’s commitment to immunology
GSK is focused on the research and development of medicines for immune-mediated diseases, such as lupus and rheumatoid arthritis, that are responsible for a significant health burden to patients and society. Our world-leading scientists are focusing research on the biology of the immune system with the aim to develop immunological-based medicines that have the potential to alter the course of inflammatory disease. As the only company with a biological treatment approved for adult and paediatric lupus, GSK is leading the way to help patients and their families manage this chronic, inflammatory autoimmune disease. Our aim is to develop transformational medicines that can alter the course of inflammatory disease to help people live their best day, every day.
Serving paediatric patients
We are committed to bringing our specialty biologic medicines to paediatric patients who have limited treatment options. We are currently progressing regulatory reviews of two different medicines for children with severe eosinophilic asthma and lupus, reinforcing our commitment to serving an unmet need with these medicines that are proven to be effective in adults.
Important Safety Information for belimumab
The following Important Safety Information is based on a summary of the European Summary of Product Characteristics. 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.
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.
Depression and suicidality: In controlled clinical intravenous and subcutaneous studies, psychiatric disorders (depression, suicidal ideation and behaviour including suicides) have been reported more frequently in patients receiving Benlysta. Assess the risk of depression and suicide considering the patient’s medical history and current psychiatric status before treatment with Benlysta and continue to monitor patients during treatment. Advise patients (and caregivers where appropriate) to contact their health care provider about new or worsening psychiatric symptoms. In patients who experience such symptoms, treatment discontinuation should be considered.
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.
Malignancies and lymphoproliferative disorders: Caution in patients with a history of malignancy or who develop malignancy whilst receiving treatment.
Pregnancy and lactation:
Women of childbearing potential must use effective contraception during Benlysta treatment and for at least 4 months after the last treatment. Limited data on use in pregnant women. Should not to be used unless the potential benefit justifies the potential risk to the foetus. 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, suicidal behaviour, suicidal ideation. Rare: Delayed-type, non-acute hypersensitivity reactions. See Summary of Product Characteristics for full details.
GSK is a science-led global healthcare company with a special purpose: to help people do more, feel better, live longer. For further information please visit www.gsk.com/about-us/.
- Brunner H et al. Efficacy and Safety of Intravenous Belimumab in Children with Systemic Lupus Erythematosus. American College of Rheumatology 2018 Abstract 2867
- Lupus Foundation of America. What is lupus? Available at: https:// resources.lupus.org/entry/what-is-lupus Last accessed March 2019
- Brunner HI et al. Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum 2008;58(2):556–62.
- Tucker LB et al. Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus 2008;17(4):314–22.
- GSK data on file, Characterizing the burden of childhood-onset Systemic Lupus Erythematosus (SLE) in the United States and European Union. DoF Summary DNG # 2019N415028_00. August 2019.
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 2018.