WASHINGTON and LONDON, November 16, 2016 /PRNewswire/ --
Results from 7-year Phase III continuation study in US patients
GSK today announced results from a 7-year safety and efficacy continuation study for Benlysta® (belimumab) in patients with active, autoantibody-positive systemic lupus erythematosus (SLE). The data being presented at the 2016 American College of Rheumatology/Association for Rheumatology Health Professionals Annual Meeting (ACR/AHRP) indicates that the long-term control of disease activity seen in patients receiving belimumab plus standard of care (SoC), shows meaningful benefits in their daily lives, including improvements in health-related quality of life (HRQoL) and fatigue, a common and debilitating symptom of SLE.
Results from the continuation study of patients who completed BLISS-76, one of the largest Phase III pivotal clinical trials conducted with intravenously administered belimumab in SLE, showed that long-term treatment with belimumab was generally well tolerated and provided effective control of patients' disease activity. By study Year 7, 75.6% of patients showed a response to treatment, as measured by the SRI4 (Systemic Lupus Responder Index). The study also assessed HRQoL using the SF-36, a measure commonly used to capture changes in quality of life across various domains of physical and mental health. By Study Year 6, the mean change from baseline in the physical (4.79 units) and mental component score (2.71 units) of the SF-36 exceeded the generally accepted minimum clinically important difference (MCID) for improvement. Furthermore, mean changes from baseline in SF-36 domain scores exceeded the MCID in 6 of the 8 domains: bodily pain, general health, physical functioning, role physical, social functioning, and vitality. Patients receiving long-term treatment with belimumab also reported continued benefits in fatigue (mean improvements of 3.70 units in FACIT-F score).
Dr. Ravi Rao, Immuno-Inflammation Medical Head, GSK, said: "Persistent disease activity can have serious long-term consequences for lupus patients, greatly impacting their day-to-day lives and affecting both their ability to function physically and socially. We have known that Benlysta is effective in reducing disease activity, but until recently data for Benlysta in SLE studies exploring the longer-term effects of treatment has been limited. These data confirm that Benlysta provides continued control of disease activity over the long-term and that this translates into meaningful benefits experienced by patients living with this chronic condition."
The incidence of adverse events remained stable or declined throughout the continuation study and were consistent with data from the Phase 2 extension study and the known profile of belimumab in patients with SLE.
About the Study
This was an open-label extension study (GSK study 112233; NCT00724867) of patients who completed BLISS-76 in the US. BLISS-76 was a randomised, controlled trial in 819 patients at 136 clinical sites in 19 countries, primarily in North America and Europe. The primary efficacy endpoint was the patient response rate at Week 52 as measured by the SLE Responder Index, a composite measure of reduction in disease activity.
In the continuation study, 268 patients comprised the modified intent-to-treat (MITT) population; 140 patients completed the study (52.2%) and 128 (47.8%) withdrew (patient request, 24.2%; AE, 19.5%). The percentage of patients who withdrew from the study did not exceed 15% in any given year interval. Overall, there were no trends of clinical concern with regard to subject withdrawal over time for any given withdrawal reason.
Patients received the same dose of belimumab as in BLISS-76 (1 or 10 mg/kg IV, every 28 days) plus SoC; patients who had previously received placebo received belimumab 10 mg/kg IV. Following licensing of belimumab, the dose for patients who received belimumab 1 mg/kg was increased to 10 mg/kg. Primary outcome measures included long-term safety, assessed by adverse event (AE) frequency and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) evaluated every 48 weeks (Study Year). Other assessments included SLE Responder Index (SRI), health-related quality of life (Short Form-36v2, Medical outcomes Survey) and fatigue (Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue).
SRI response rate is a composite measure which comprises a number of elements including:
- ≥ 4 point reduction from baseline in SELENA SLEDAI score AND
- no worsening (increase of < 0.30 points) in Physician's Global Assessment (PGA) AND
- no worsening in disease activity as measured by British Isles Lupus Assessment Group of SLE Clinics (BILAG) organ domain score (No new A or 2 new BILAG B organ domain scores compared with baseline)
About Benlysta® (belimumab), for injection, for intravenous use only
Benlysta is the first medicine specifically developed and approved for SLE in over 50 years. 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 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 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
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 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.
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, 5/673 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: Category C. Benlysta should be used during pregnancy only if the potential benefit outweighs the risk. Women of childbearing potential should use adequate contraception during treatment with Benlysta and for at least 4 months after the last dose.
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.
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.
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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 'Risk factors' in the company's Annual Report on Form 20-F for 2015.
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