Takeda Announces Positive Phase III Data for NINLARO™ (ixazomib) as First-Line Maintenance Therapy in Multiple Myeloma

June 13, 2020 News /BioValleyBIOON/ -- Japanese pharmaceutical company Takeda recently announced the results of two clinical studies evaluating the oral proteasome inhibitor Ninlaro (ixazomib) for the treatment of multiple myeloma (MM) at the 25th Congress of the European Hematology Association (EHA). The studies include the Phase III TOURMALINE-MM4 study on single-agent first-line maintenance therapy, and the US MM-6 study on switching between proteasome inhibitors within the same class.

TOURMALINE-MM4 (NCT02312258) Study:is a randomized, double-blind, placebo-controlled Phase III study that enrolled a total of 706 newDiagnosisfor multiple myeloma, treatment-naïveStem CellsIn patients who had undergone transplantation and completed 6–12 months of initial therapy, achieving a partial response or better, the impact of Ninlaro as single-agent maintenance therapy versus placebo on progression-free survival (PFS) was evaluated.

The results demonstrated that the study met its primary endpoint: patients in the Ninlaro group achieved a statistically and clinically significant improvement in progression-free survival (PFS) compared with the placebo group (median PFS: 17.4 months vs. 9.4 months; HR=0.659; 95% CI; p<0.001), corresponding to a 34.1% reduction in the risk of disease progression or death. Currently, data for the secondary endpoint of overall survival (OS) are not yet mature, and follow-up is ongoing.

In this study, Ninlaro maintenance therapy demonstrated a favorable safety profile and had no adverse impact on patients' quality of life. The safety profile of Ninlaro was consistent with previously reported results from Ninlaro monotherapy, with no new safety findings identified. The most common treatment-emergent adverse events (TEAEs) were nausea, vomiting, diarrhea, rash, peripheral neuropathy (PN), and pyrexia.

36.6% of patients in the Ninlaro treatment group and 23.2% of patients in the placebo group experienced ≥ Grade 3 TEAEs. New primary malignanciesTumorThe incidence rate was 2% in the Ninlaro group and 6.2% in the placebo group. The proportion of patients who discontinued treatment due to TEAEs was low, at 12.9% in the Ninlaro group and 8% in the placebo group. During the study, the mortality rate was 2.6% in the Ninlaro group and 2.2% in the placebo group.

Meletios Dimopoulos, MD, Professor at the Medical School of the National and Kapodistrian University of Athens and principal investigator of the TOURMALINE-MM4 trial, stated: “There is a strong unmet need for additional maintenance therapy options in multiple myeloma, given the limited number of currently approved maintenance regimens. Data from this Phase III trial reinforce the role of proteasome inhibition as a maintenance therapy strategy and demonstrate that longer-duration treatment can not only prolong but also deepen responses. These findings may have significant implications for patients who currently have limited therapeutic options, typically those ineligible forStem Cellsthe situation faced by transplant patients.”

US MM-6 (NCT03173092) Study:This is an ongoing, open-label, single-arm, multicenter study in newDiagnosisConducted in patients with multiple myeloma who received a triplet induction regimen based on another proteasome inhibitor, bortezomib (administered via intravenous infusion) (bortezomib + lenalidomide + dexamethasone), this study evaluated the efficacy and safety of switching within the same drug class, specifically transitioning from the bortezomib-based triplet regimen to the Ninlaro-based triplet regimen (Ninlaro [oral administration] + lenalidomide + dexamethasone). The primary endpoint was progression-free survival (PFS), and key secondary endpoints included duration of treatment (DOT) and duration of response (DOR).

Data show that transitioning from parenteral bortezomib therapy to a Ninlaro-based regimen, administered by patients at home, allows for long-term use of proteasome inhibitors and results in an increase in the overall response rate (ORR) from 62% to 70% and in the complete response rate (CR) from 4% to 26%. These data indicate that switching within the same drug class—from intravenous bortezomib to oral Ninlaro—achieves favorable efficacy without compromising patients’ quality of life. In this study, Ninlaro demonstrated a favorable safety profile, with no unexpected safety signals identified.

TakedaTumorChristopher Arendt, Head of the Therapeutic Area, stated: “The positive results from the Phase III TOURMALINE-MM4 trial demonstrate that, in patients who are not eligible forStem CellsIn newly diagnosed multiple myeloma patients undergoing transplantation, Ninlaro as maintenance therapy significantly improved progression-free survival. Results from the US MM-6 trial demonstrated that Ninlaro is an effective, well-tolerated, and convenient treatment for multiple myeloma, enabling prolonged proteasome inhibitor therapy and achieving better therapeutic outcomes.

Ninlaro is the first oral proteasome inhibitor marketed globally, initially approved in the United States in November 2015.FDAApproved in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. To date, Ninlaro has been approved in more than 60 countries, including the United States, Japan, and the European Union, with regulatory submissions under review in more than 10 additional countries. Currently, Ninlaro is being developed for use in multiple treatment settings for multiple myeloma.

Multiple myeloma is a hematologic malignancyTumor, which originates from plasma cells, a type of white blood cell produced in the bone marrow. Normal plasma cells are responsible for producing antibodies that fight infection, whereas cancerous plasma cells—myeloma cells—proliferate extensively in the bone marrow and release an antibody known as paraprotein, which causes disease symptoms including bone pain, frequent or recurrent infections, and fatigue,AnemiaSymptoms. These malignant plasma cells can affect multiple bones in the human body and may lead to serious health issues impacting the skeletal system, immune system, kidneys, and red blood cell count. The typical clinical course of multiple myeloma includes a symptomatic phase followed by periods of remission. It is estimated that there are over 230,000 multiple myeloma patients worldwide, with 114,000 new cases diagnosed annually. (Bioon.com)

Original Source: Takeda Presents Positive Data from Clinical Trial Evaluating Oral NINLARO™ (ixazomib) in Multiple Myeloma as a First-Line Maintenance Therapy