The FDA recently granted priority review status to ixazomib (Takeda) for the treatment of relapsed or refractory multiple myeloma.
The US Food and Drug Administration recently granted priority review status to ixazomib (Takeda) for the treatment of relapsed or refractory multiple myeloma.
Ixazomib is an oral proteasome inhibitor that was granted orphan drug designation for multiple myeloma in 2011. Priority review status will now allow the FDA to expedite review of the drug.
The ixazomib application for approval is based primarily on the results of the interim analysis of the phase III TOURMALINE-MM1 study. Results of this analysis were announced by the manufacturer in February and showed that the drug had met the primary endpoint of the study, improving progression-free survival.
TOURMALINE-MM1 included 722 patients with relapsed or refractory multiple myeloma who had received one to three prior therapies. Patients who relapsed after prior treatment with lenalidomide were excluded.
Patients were assigned to treatment with ixazomib plus lenalidomide and dexamethasone or to placebo plus lenalidomide and dexamethasone. According to a press release issued by Takeda, patients taking ixazomib plus lenalidomide and dexamethasone had significantly improved progression-free survival compared to patients who received placebo.
Data from the phase I and phase II evaluations of ixazomib were published in 2014 in Lancet Oncology. The phase I study was designed to establish the maximum tolerated dose of the drug. It included 65 patients with ECOG status of 0–2 and tested ixazomib plus lenalidomide and dexamethasone. Four dose-limiting toxicities occurred: one at 2.97 mg/m2 and three at 3.95 mg/m2. A dose of 2.23 mg/m2 was recommended for phase II evaluation.
In the phase II evaluation the ixazomib dose was converted to a fixed dose of 4 mg. At this dose, 37 of 64 patients had a very good partial response or better, and 17 patients had a complete response. Sixty-three percent of patients had grade 3 or higher adverse events, but grade 3 or higher peripheral neuropathy was only reported in 6% of patients.
There are currently several additional phase III trials evaluating ixazomib, including trials looking at the drug in newly diagnosed multiple myeloma, in newly diagnosed multiple myeloma as a maintenance therapy following induction therapy and stem cell transplant, and in AL amyloidosis.