FDA approved Ninlaro (ixazomib), developed by Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. Ixazomib is the first approved oral proteasome inhibitor.

The approval was based on an improvement in progression- free survival in a multicenter, randomized, double-blind, placebo-controlled trial enrolling 722 patients with multiple myeloma who had received one to three prior lines of therapy. Patients were randomized in a 1:1 ratio to either the combination of ixazomib, lenalidomide and dexamethasone (n=360) or the combination of placebo, lenalidomide and dexamethasone (n=362). Patients continued treatment until disease progression or unacceptable toxicity.

The trial showed a statistically significant improvement in PFS. The median PFS on the combination arm of ixazomib, lenalidomide and dexamethasone was 20.6 months (95% CI: 17.0, NE) compared to a median PFS of 14.7 months (95% CI: 12.9, 17.6) on the combination arm of placebo, lenalidomide and dexamethasone (PFS HR 0.74, 95% CI: 0.59, 0.94; p=0.012).