GSK has announced results from the BLISS-SC Phase III pivotal study in patients with active, autoantibody-positive systemic lupus erythematosus (SLE). These results, which are being presented at the American College of Rheumatology/Association for Rheumatology Health Professionals Annual Meeting, showed that Benlysta® (belimumab) 200mg administered weekly via subcutaneous injection plus standard of care (SoC), showed significantly greater reductions in disease activity compared to placebo plus SoC.
For the primary efficacy endpoint (Systemic Lupus Erythematosus Responder Index (SRI) at Week 52), significantly more patients treated with belimumab administered subcutaneously plus SoC (60.8%) showed reduced disease activity compared to placebo plus SoC (48.47%, p=0.0011). SRI is a comprehensive composite endpoint measure, used in the pivotal Phase III BLISS clinical trial programme for belimumab administered intravenously. The SRI components measure reduction in disease activity defined as clinical improvement (SELENA-SLEDAI) with no significant worsening in any organ system (BILAG) and no worsening in overall patient condition (PGA).
For the two pre-specified secondary efficacy endpoints, the study showed that the time to severe flare was significantly delayed in patients receiving belimumab administered subcutaneously plus SoC (170 days, p=0.0003) compared to those on placebo plus SoC (116.5 days). In addition, in patients receiving more than 7.5mg/day of prednisone (n=503),18.2% of patients receiving belimumab administered subcutaneously plus SoC in the study were able to reduce their steroid dose by 25% or more to
"Despite use of current standard of care, such as glucocorticosteroids and immunosuppressants, about 60% of lupus patients continue to experience persistent symptoms and severe disease flares", said Paul-Peter Tak, Senior Vice-President and Head of the Immuno-Inflammation Therapy Area Unit at GSK. "This is GSK's third successful Phase III study of belimumab in patients with lupus, the results of which reinforce our belief in the BLyS pathway as a means of reducing underlying disease activity. On the basis of these data, we expect to progress towards global regulatory filings for a belimumab subcutaneous formulation, which if approved, will provide appropriate patients with a new approach to treatment administration."
The overall safety profile of belimumab in BLISS-SC was consistent with that observed in the two previous BLISS studies (BLISS-52 and BLISS-76). The overall incidence of treatment-related adverse events (AEs) was 31.3% with belimumab administered subcutaneously plus SoC vs 26.1% with placebo plus SoC [the most common of which were infections/infestations (belimumab administered subcutaneously plus SoC 18.7% vs placebo plus SoC 18.9%) and general disorders and administration site conditions, primarily injection site-related events (belimumab administered subcutaneously plus SoC 6.3% vs placebo plus SoC 3.6%)]. Incidence of AEs leading to discontinuation in the belimumab administered subcutaneously plus SoC group was 7.2% compared to 8.9% with placebo plus SoC. The percentage of patients experiencing a serious AE was 10.8% with belimumab administered subcutaneously plus SoC compared with 15.7% with placebo plus SoC. A total of 5 deaths were reported; 3 (0.5%) with belimumab administered subcutaneously plus SoC, and 2 (0.7%) with placebo plus SoC. The overall incidence of death in all the randomised controlled studies of belimumab in lupus was 0.7% for the belimumab group, which is similar to that in the placebo group (0.5%).
Belimumab subcutaneous formulation is currently not approved for use anywhere in the world.
About the BLISS-SC study
BLISS-SC builds on a robust clinical trial programme for belimumab, which is the largest conducted in SLE to date1-3. BLISS-SC is a Phase III, multi-centre, randomised, double-blind, placebo-controlled, 52-week study to evaluate the efficacy and safety of belimumab administered subcutaneously to patients with active, autoantibody-positive SLE who are receiving standard therapy. The primary efficacy endpoint is the SRI response rate at Week 52. This 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
- 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)
- Drop outs and treatment failures were included as non-responders in the primary analysis.
The two major secondary efficacy endpoints included the time to first severe flare (as measured by the modified SLE Flare Index (SFI)) and the percentage of patients whose average prednisone dose was reduced by ≥ 25% from baseline to ≤ 7.5 mg/day during weeks 40 to 52 in patients receiving greater than 7.5 mg/day at baseline. Of the 836 patients enrolled into the study, 556 were randomised to receive belimumab plus SoC and 280 were randomised to placebo plus SoC. Ninety-four percent of the overall population in the study were female.