FDA approved ixazomib (Ninlaro, Takeda) in combination with lenalidomide and dexamethasone in November 2015 to treat patients with multiple myeloma who have received at least one prior therapy. Ixazomib was granted priority review and orphan drug designations by FDA.
When treating patients with relapsed multiple myeloma, 3-drug regimens have been shown to be superior to 2-drug regimens. Yet current treatment options often have many bothersome and dose-limiting side effects. Ixazomib is the first FDA-approved oral proteasome inhibitor. Ixazomib inhibits proteasomes that affect multiple myeloma cell growth and survival. Combined with lenalidomide and dexamethasone, this approval provides an all oral-drug regimen for patients with refractory or relapsed multiple myeloma.
Ixazomib approval was based on a double blind, placebo-controlled, phase 3 trial that enrolled 722 patients who had relapsed, refractory, or relapsed and refractory multiple myeloma.1 Of note, patients who had refractory disease to lenalidomide or proteasome inhibitor-based therapy were not eligible. Patients received either oral ixazomib 4 mg or placebo on days 1, 8, and 15 of a 28-day cycle: both groups also received 25 mg of oral lenalidomide on days 1 through 21 and 40 mg of oral dexamethasone on days 1, 8, 15, and 22.
The primary endpoint—median progression-free survival—was measured at 20.6 months in the ixazomib group and 14.7 months in the placebo group. The hazard ratio for disease progression or death was 0.74 (95% confidence interval, 0.59 to 0.94; P=0.01). 129 events of disease progression or death occurred in the ixazomib group vs 157 in the placebo group. Subgroup analyses showed similar progression-free survival times in patients with a poor prognosis, high-risk cytogenetic abnormalities, and other high risk features.