"Motivation for this imputation scheme was to take a very conservative approach for medication failure subjects who the clinical team did not feel would have unquestionably proceeded to be an efficacy failure had they not received the prohibited medication," the FDA’s briefing document explains.
Based on these assignments the sensitivity analysis found the results for study 1057 to be generally consistent with the primary efficacy analysis.
However, for Study 1056, the difference in treatment effect between the 10 mg/kg belimumab and placebo arms is only marginally statistically significant. This suggests that results of the primary efficacy analyses are "dependent on the disproportional occurrence of medication failures" in the placebo group of that study.
The apparently higher need for rescue medication in the placebo group can be taken as an unofficial signal of efficacy for belimumab, the agency acknowledges. But, the agency concludes, "the clinical importance of taking a prohibited medication relative to the clinical importance of the primary efficacy end point should be evaluated and kept in mind in interpreting the primary efficacy results."
Suicidality an Unexpected Addition to the Safety Issues
In addressing the safety issues that will be presented to the advisory panel, the FDA noted the somewhat unexpected increase in the risk for neuropsychiatric adverse events – suicide in particular. The safety database included 2,133 patients in the two phase III trials plus a randomized, placebo-controlled phase II study (L02).
Two suicides occurred among belimumab patients during the studies, with another in the safety extension of L02. Four cases of suicide attempts or suicidal ideation occurred in belimumab patients. Depression was the most serious adverse event in the psychiatric disorder category. '
Other safety issues to be discussed at the committee are the potential for death – a rate of 0.79 per 100 patient-years for belimumab patients versus 0.43 for those on placebo – as well as malignancies and infections, which have been recognized risks for the drug.
The advisory committee’s review of the efficacy and safety of belimumab comes in the context of Benlysta having the potential to be the first new drug for lupus in 50 years. The prescriber and patient communities are eager for a new therapy.
Elsevier Global Medical News and "The Pink Sheet" are both published by Elsevier.