Final efficacy and safety results from phase II continuation study
Issued: Madrid, Spain and London, UK
GSK today announced results from a 10-year continuation study, which showed that Benlysta (belimumab) plus standard of care prolonged control of disease activity in patients with active systemic lupus erythematosus (SLE). Benlysta is a biologic medicine specifically developed and approved for SLE and this is the longest study to measure efficacy and safety of an SLE therapy.
The study, presented at the Annual European Congress of Rheumatology (EULAR) 2017, showed that the percentage of those responding to treatment with belimumab increased over time, with an overall response of 65.1% (n=126) at Year 10 as measured by SRI (SLE Responder Index), a composite efficacy measure in lupus. Overall, patients were able to decrease their corticosteroid dose over time from baseline to Year 10. Of patients receiving more than 7.5 mg/day baseline prednisone, 32.6% (14/43) decreased their dose to ≤7.5 mg/day by Year 10. 9.5% (9/95) of patients receiving baseline prednisone ≤7.5 mg/day had a dose increase to more than 7.5 mg/day. Corticosteroid use is associated with significant side effects, so reduction in dose is an important goal in SLE management.
David Roth, Medicines Development Leader, R&D Immuno-Inflammation at GSK, said “In lupus, the underlying disease is always present and symptoms can erupt, or flare, without warning, making it incredibly difficult to manage everyday life. Unlike most treatments used for SLE, belimumab has a specific mode of action that targets the underlying disease process. It has consistently proven its effectiveness, with four successful pivotal trials in SLE and data now shows that the disease control is sustained, helping to stabilise day-to-day symptoms and improve outcomes for patients in the longer-term.”
The prevalence rate of AEs and SAEs also remained relatively stable over time and consistent with the known profile for belimumab.
About the study
This was a multicentre, open-label, continuation trial (BEL 112626; NCT00583362) of belimumab 10 mg/kg plus standard of care in patients who completed the phase II parent study – a double-blind, placebo-controlled, 52-week study of belimumab 1, 4 or 10 mg/kg and 24-week extension of belimumab (placebo switched to 10 mg/kg; belimumab same dose or switched to 10 mg/kg). Of 298 patients in the continuation trial, 131 (44%) remained at Year 10. Total belimumab exposure was 2,154 patient-years. Disease activity, defined by SELENA-SLEDAI score, was analysed in patients with active SLE at baseline of the initial study.
The population that entered the long-term continuation study and continued throughout 10 years was potentially enriched with patients who responded to or tolerated belimumab [i.e. these were patients who had an improvement in Physician’s Global Assessment (PGA) compared with baseline or Week 52 and had no severe SLE flare in the last 30 days of the 24-week extension period].
As there is no matched-control group, no treatment comparison for the long-term efficacy and safety data can be made.
About Benlysta (belimumab), for injection, for intravenous use only
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 only.
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 http://www.ema.europa.eu/
Benlysta is indicated 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. It is a chronic, incurable autoimmune disease producing autoantibodies that can attack almost any system in the body.
Important Safety Information for belimumab
Please consult the full Prescribing Information for all the labelled safety information for Benlysta (belimumab) for injection, for intravenous use only.
Benlysta is contraindicated in patients who have had anaphylaxis with belimumab.
WARNINGS AND PRECAUTIONS
There were more deaths reported with Benlysta than with placebo during the controlled period of the clinical trials. Out of 2133 patients in 3 clinical trials, a total of 14 deaths occurred in the following groups: 3/675 in placebo, 6/673 in Benlysta 1 mg/kg, 0/111 in Benlysta 4 mg/kg, and 6/674 in Benlysta 10 mg/kg. No single cause of death predominated. Etiologies included infection, cardiovascular disease, and suicide.
Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents, including Benlysta. Caution should be exercised when considering use in patients with a history of chronic infections. Patients receiving therapy for a chronic infection should not receive Benlysta. Consider interrupting therapy with Benlysta in patients who develop a new infection while receiving Benlysta. The most frequent serious infections included pneumonia, urinary tract infection, cellulitis, and bronchitis.
Progressive Multifocal Leukoencephalopathy (PML): Cases of JC virus-associated PML resulting in neurological deficits, including fatal cases, have been reported in patients with SLE receiving immunosuppressants, including Benlysta. Patients presenting with new-onset or deteriorating neurological signs and symptoms should be evaluated for PML by an appropriate specialist. If PML is confirmed, consider stopping immunosuppressant therapy, including Benlysta.
The impact of treatment with Benlysta on the development of malignancies is not known. The mechanism of action of Benlysta could increase the risk of malignancies.
HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS) AND INFUSION REACTIONS
Acute hypersensitivity reactions, including anaphylaxis and death, have been reported with Benlysta. These events generally occurred within hours of the infusion; however, they may occur later. Non-acute hypersensitivity reactions including rash, nausea, fatigue, myalgia, headache, and facial edema, have been reported and typically occurred up to a week following the most recent infusion. Hypersensitivity, including serious reactions, has occurred in patients who have previously tolerated infusions of Benlysta. Patients with a history of multiple drug allergies or significant hypersensitivity may be at increased risk. Some patients received premedication; however, there is insufficient evidence to determine whether premedication diminishes the frequency or severity of these reactions.
Healthcare providers should be aware of the risk of hypersensitivity reactions, which may present as infusion reactions, and monitor patients closely. Manifestations of hypersensitivity included hypotension, angioedema, urticaria or other rash, pruritus, and dyspnea. In the event of a serious hypersensitivity reaction, discontinue Benlysta immediately and administer appropriate medical therapy. Infusion-associated adverse events were also reported. Serious infusion reactions included bradycardia, myalgia, headache, rash, urticaria, and hypotension. In the event of an infusion reaction, the infusion rate may be slowed or interrupted.
Patients should be informed of the signs and symptoms of an acute hypersensitivity reaction and be instructed to seek immediate medical care should a reaction occur.
In clinical trials, psychiatric events (primarily depression, insomnia, and anxiety) were reported more frequently with Benlysta than with placebo. Serious psychiatric events, serious depression, and two suicides were also reported. It is unknown if treatment with Benlysta is associated with increased risk for these events. Patients should be instructed to contact their healthcare provider if they experience new or worsening depression, suicidal thoughts, or other mood changes.
Live vaccines should not be given for 30 days before or concurrently with Benlysta. Benlysta may interfere with the response to immunisations.
USE WITH BIOLOGIC THERAPIES OR IV CYCLOPHOSPHAMIDE
Benlysta has not been studied in combination with other biologic therapies, including B-cell targeted therapies, or IV cyclophosphamide. Therefore, use of Benlysta is not recommended in combination with these therapies.
The most common serious adverse reactions were serious infections (6.0% and 5.2% in patients receiving Benlysta and placebo, respectively). Adverse reactions, regardless of causality, occurring in at least 3% of patients with SLE who received Benlysta 10 mg/kg and placebo respectively and, at an incidence at least1% greater than that observed with placebo in the 3 controlled studies were: nausea 15% and 12%; diarrhea 12% and 9%; pyrexia 10% and 8%; nasopharyngitis 9% and 7%; bronchitis 9% and 5%; insomnia 7% and 5%; pain in extremity 6%, and 4%; depression 5% and 4%; migraine 5% and 4%, pharyngitis 5% and 3%; cystitis 4% and 3%; leukopenia 4% and 2%; viral gastroenteritis 3% and 1%.
Other Important Information for Benlysta
USE IN SPECIFIC POPULATIONS
Pregnancy: There are insufficient data on use of Benlysta in pregnant women to determine whether there is drug-associated risk for major birth defects or miscarriage. Women of childbearing potential should use effective contraception during treatment and for at least 4 months after the final treatment.
Lactation: There is no information available on the presence of belimumab in human milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Benlysta and any potential adverse effects on the breastfed child from Benlysta or from the underlying maternal condition.
Populations not studied
Benlysta has not been studied in the following patient groups, and is not recommended in patients with:
- severe active central nervous system lupus
- severe active lupus nephritis
- a history of, or current, hepatitis B or C
- hypogammaglobulinaemia (IgG <400 mg/dl) or IgA deficiency (IgA <10 mg/dl)
- a history of major organ transplant or hematopoietic stem /cell /marrow transplant or renal transplant.
Effect in black/African American patients: In exploratory analyses of 2 Phase III trials, response rates were lower for black patients (N=148) in the groups receiving Benlysta relative to black patients in the placebo group. In the Phase II trial, black patients (N=106) in the groups receiving Benlysta did not appear to have a different response than the rest of the study population. Although no definitive conclusions can be drawn from these analyses, caution should be used when considering Benlysta for black/African American patients.
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