Regulatory Decision Summary for Benlysta

Lupus nephritis (LN) is a common manifestation of systemic lupus erythematosus (SLE) associated with high rates of progression to end-stage-renal disease despite immunosuppressive therapy with current standard of care regimens that carry risk of toxicity and/or infection.

In the pivotal trial BEL114054, the addition of Benlysta to standard of care immunosuppression (with high dose corticosteroids and mycofenolate mofetil (MMF) or cyclophosphamide (CYC) / azathioprine (AZA)) was associated with a higher rate of renal response to treatment in subjects receiving belimumab versus placebo. The sponsor provided a clinical rationale for their choice of primary efficacy endpoint of Primary Efficacy Renal Response (PERR), and efficacy data were considered sufficiently reliable. A benefit from the addition with the addition of Benlysta to standard therapy was demonstrated by PERR as well as by the key secondary efficacy measures of complete renal response and time to renal event or death. The consistent finding of a benefit across efficacy measures supports a benefit in the overall population of patients treated for LN.

Subjects treated with Benlysta experienced a frequency of infections and adverse events that were higher than observed in prior studies of Benlysta for the treatment of SLE, particularly in the first 24 weeks of treatment, after which the frequency of infections and adverse events were consistent to prior studies in the general SLE population. This was reasonable given the aggressive standard-of-care immunosuppression during induction therapy in the LN trial, and the underlying disease that predisposes these patients to complications. The most common adverse events observed amongst subjects with LN treated with Benlysta were infections. The frequency of serious infections and adverse events were similar between the placebo-treated and Benlysta-treated group. Clinical review suggests the benefits of Benlysta in improving renal response to treatment are not outweighed by additional risks.

Risk mitigation strategies include appropriate product labelling, and submission of Periodic Benefit-Risk Evaluation Report (PBRER) are considered appropriate at this time.