[Pharmacological characteristics and clinical study results of the oral proteasome inhibitor ixazomib (NINLARO capsules; 2.3 mg, 3 mg, and 4 mg)].

Ixazomib (Ninlaro capsule) is an oral small molecule 20S proteasome inhibitor created by Millennium Pharmaceuticals, Inc (Takeda Oncology Company). Ubiquitin proteasome system is a major regulatory system for maintaining protein homeostasis, and an important mechanism for degrading proteins, such as those involved in proliferation regulation, cell cycle regulation and apoptosis, in cells. Ixazomib selectively and reversibly binds to the β5 subunit of the 20S proteasome, inhibits its chymotrypsin-like activity, and thereby accumulates ubiquitinated proteins. It induces ER stress and apoptosis of myeloma cells. The phase 3, randomized, double-blind, multicenter global study (TOURMALINE-MM1) in patients with relapsed and/or refractory multiple myeloma, who have received 1 to 3 prior lines of therapy, showed that addition of ixazomib to lenalidomide-dexamethasone (ixazomib-Rd) demonstrated significant improvement in progression-free survival (hazard ratio = 0.742, P = 0.012) versus placebo-Rd (20.6 vs. 14.7 months in the median) (data cut-off as of October 30, 2014). Ixazomib has been approved by the United States Food and Drug Administration in November 2015, and the European Medicines Agency in November 2016 for the treatment of multiple myeloma (MM) patients who have received at least one prior therapy. In Japan, ixazomib was approved for the treatment of relapsed and/or refractory MM in March, 2017. It is expected to demonstrate that the oral proteasome inhibitor ixazomib is an effective and convenient treatment option in clinical practice.