Ninlaro (ixazomib) is an oral prescription therapy developed by Takeda for the treatment of multiple myeloma. Prescribed in combination with Revlimid (lenalidomide) and the corticosteroid dexamethasone, the medication is given to people with multiple myeloma who have had at least one prior treatment.
The trio therapy — Ninlaro, Revlimid, and dexamethasone, known as NRD — was approved by the U.S. Food and Drug Administration (FDA) in 2015 following the results of the Phase 3 TOURMALINE-MM1 clinical trial (NCT01564537). That same trial led the European Medicines Agency (EMA) to grant conditional marketing authorization for the NRD combination in 2016.
How does Ninlaro work?
Ninlaro is a proteasome inhibitor. These work by targeting cellular components called proteasomes that are required to break down and recycle damaged proteins inside cells. A functioning proteasome can help repair damaged proteins, which can promote cancer cell growth.
The inhibition of proteasomes using treatments such as Ninlaro ensures that damaged proteins, which are often the result of aggressive cell division in cancer cells, are not repaired. That then results in their accumulation, causing the death of cancer cells.
Ninlaro in clinical trials
The safety and efficacy of Ninlaro in treating multiple myeloma were demonstrated in several clinical trials.
The TOURMALINE-MM1 trial showed a very good overall response rate (ORR) of 78% in patients treated with Ninlardo compared with 72% in those treated with placebo. The results also showed a partial response rate of 48% in the Ninlardo group compared with 39% in the placebo group. The study found that treatment with Ninlardo led to significantly longer progression-free survival in the treatment group compared to the placebo group — about 20.6 months versus just 14.7 months. The study is still ongoing and is expected to be fully completed in December 2020.
A Phase 2 clinical trial (NCT02046070), completed in 2018, was designed to determine the safety and response rate of Ninlardo in combination with cyclophosphamide and dexamethasone (ICd). That study had enrolled newly diagnosed multiple myeloma (NDMM) patients, older than 65, who had not received prior therapy and were ineligible for autologous hematopoietic stem cell transplantation (AHSCT). ICd was well-tolerated in these patients with no late-onset toxicity, the study found.
A new study, currently underway, is examining the safety and efficacy of the NRD combination in 701 NDMM patients who are not eligible for AHSCT. That Phase 3 clinical trial (NCT01850524), called TOURMALINE-MM2, is expected to be completed in February 2021.
A Phase 3 clinical trial (NCT02181413) called TOURMALINE-MM3 also is underway to determine the effect of Ninlaro maintenance therapy in people with NDMM following AHSCT. Initial results have shown that Ninlaro reduced disease progression by 28% in these patients. However, about 42% of the enrolled participants reported adverse effects. The trial is expected to be completed in June 2025.
Another Phase 3 clinical trial (NCT02312258) also currently underway is called TOURMALINE-MM4. This study, expected to be completed in October 2024, is assessing the efficacy of Ninlaro as maintenance therapy in NDMM patients who have responded to initial therapy and have not undergone AHSCT. Preliminary results have shown that Ninlaro prolonged progression-free survival compared with the placebo.
The dosing cycle for NRD lasts about four weeks, with Ninlaro taken on the starting day of the week for three weeks, along with Revlimid and dexamethasone. It may take up to one month from the onset of the regimen for the first response to become evident.
The side effects of taking Ninlaro include thrombocytopenia (low platelet counts), gastrointestinal problems, nerve problems — which can include weakness, pain, numbness, and a burning sensation in the hands and feet — swelling, and skin and liver problems.
Ninlaro is should not be used by pregnant or breastfeeding women.
Last updated: Nov. 26, 2019
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