GSK announced positive efficacy and safety data from a pivotal study of patients with systemic lupus erythematosus (SLE) in Northeast Asia (Japan, China and South Korea). In the study, being presented at the 2016 American College of Rheumatology/Association for Rheumatology Health Professionals Annual Meeting (ACR/AHRP), Benlysta achieved the primary and all four pre-specified secondary endpoints with statistical significance. The information obtained will be used to submit files for the regulatory approval of belimumab in Japan and China in the next few months.
For the primary efficacy endpoint (SLE Responder Index at Week 52), significantly more of the patients on belimumab 10mg/kg administered intravenously (54%) achieved reduced disease activity compared to those on placebo (40%) (Odds Ratio: 2.03; 95% CI: 1.43-2.88; p<0.0001). SRI is a comprehensive composite endpoint measure, the components of which measure reduction in disease activity defined as clinical improvement (4-point improvement in SELENA-SLEDAI, [SS]) with no significant worsening in any organ system (BILAG) and no worsening in overall patient condition (PGA).
The benefits of belimumab were also seen for all the secondary endpoints in the study. The key secondary endpoint relating to average steroid reduction in patients with baseline dose of >7.5mg/day prednisone was significant (p=0.0228), favouring belimumab. In addition 56% of patients on belimumab achieved a =4 point reduction in SS at Week 52 (versus 42% on placebo, p=0.0001); 33% of belimumab patients achieved an SRI7 response rate (versus 23% on placebo, p=0.0099); and the belimumab group had a 50% lower risk of experiencing a severe flare versus placebo, as measured by the Severe Flare Index (p=0.0004).
The safety profile of belimumab observed in the study was consistent with that observed in previous IV and subcutaneous belimumab studies, with the overall incidence of adverse events being similar in both the belimumab (75%) versus placebo (76%) groups. Fewer serious adverse events occurred in the belimumab group compared to the placebo group (12% versus 18%). There were no deaths in the belimumab group and 1 in the placebo group. No new safety issues were identified.
David Roth, Project Lead for Benlysta at GSK, said, “Outside of South Korea, where Benlysta has already been granted approval, there is currently no approved biologic treatment option for lupus patients in Northeast Asia, so in the context of the unmet medical need in the region, this study result is extremely important. The data also reinforces our belief that the belimumab mechanism of action is central to disease activity in SLE and we are pleased that the benefit/risk profile remains favourable for patients. Based on this data and subsequent regulatory submissions, we hope to be able to make Benlysta available to more patients living with lupus in this region.”
A total of 707 patients in Japan, China and South Korea with SLE who were at least 18 years of age , with a SELENA SLEDAI score of = 8 were recruited into the phase 3, randomized, placebo-controlled, 52-week study to evaluate the efficacy and safety of 10mg/kg belimumab administered intravenously (IV) in addition to standard of care (SoC) relative to placebo. Patients received 14 doses of study medication over 48 weeks and were then evaluated at week 52 for the primary efficacy endpoint. Ninety-three per cent of the patients in both the belimumab and placebo arms of the study were female with Median disease duration of 5 years. The primary endpoint was the SLE responder index (SRI) response rate at Wk 52 (reduction =4 points in SS score; no worsening (<0.3 increase) in Physician’s Global Assessment (PGA); no new British Isles Lupus Assessment Group (BILAG A domain score or 2 new BILAG B domain scores vs baseline. Secondary endpoints included percent of patients with =4 point reduction in SS score over baseline at Wk 52, SRI7 responders (SRI where the reduction in SS is =7 points reduction rather than 4) at Wk 52, number of days of daily prednisone dose =7.5mg and/or reduced by 50% over 52 wks, and time to first severe SLE flare (using the modified SLE Flare Index).
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.
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.
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%.