General Information

Ninlaro (ixazomib) is a proteasome inhibitor.

Ninlaro is specifically indicated for use in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Ninlaro is supplied as a capsule for oral administration. The recommended starting dose of Ninlaro is 4 mg administered orally once a week on Days 1, 8, and 15 of a 28-day treatment cycle. The recommended starting dose of lenalidomide is 25 mg administered daily on Days 1 through 21 of a 28-day treatment cycle. The recommended starting dose of dexamethasone is 40 mg administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle.

Ninlaro should be taken once a week on the same day and at approximately the same time for the first three weeks of a four week cycle. Ninlaro should be taken at least one hour before or at least two hours after food. The whole capsule should be swallowed with water. The capsule should not be crushed, chewed or opened. If a dose is delayed or missed, the dose should be taken only if the next scheduled dose is ≥ 72 hours away. A missed dose should not be taken within 72 hours of the next scheduled dose. A double dose should not be taken to make up for the missed dose. If vomiting occurs after taking a dose, the patient should not repeat the dose. The patient should resume dosing at the time of the next scheduled dose.

Please see the drug label for dosing modifications.

Clinical Results

FDA Approval

The FDA approval of Ninlaro in combination with lenalidomide and dexamethasone was evaluated in a randomized, double-blind, placebo-controlled, multicenter study in 722 patients with relapsed and/or refractory multiple myeloma who had received at least one prior line of therapy. Patients who were refractory to lenalidomide or proteasome inhibitors were excluded from the study. The subjects were randomized in a 1:1 ratio to receive either the combination of Ninlaro, lenalidomide and dexamethasone or the combination of placebo, lenalidomide and dexamethasone (N=362; placebo regimen) until disease progression or unacceptable toxicity. The efficacy of Ninlaro was evaluated by progression-free survival (PFS). The group receiving Ninlaro showed a statistically significant improvement- this group lived longer without their disease worsening (average 20.6 months) compared to subjects taking the placebo regimen (14.7 months).

Mechanism of Action

Ninlaro (ixazomib) is a proteasome inhibitor. Ixazomib preferentially binds and inhibits the chymotrypsin-like activity of the beta 5 subunit of the 20S proteasome. Ixazomib induced apoptosis of multiple myeloma cell lines in vitro. Ixazomib demonstrated in vitro cytotoxicity against myeloma cells from patients who had relapsed after multiple prior therapies, including bortezomib, lenalidomide, and dexamethasone. The combination of ixazomib and lenalidomide demonstrated synergistic cytotoxic effects in multiple myeloma cell lines. In vivo, ixazomib demonstrated antitumor activity in a mouse multiple myeloma tumor xenograft model.