GSK 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.
This was an open-label extension study 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).
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.
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.
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.
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.