Takeda said that patients treated with Ninlaro in the Phase III TOURMALINE-AL1 study failed to see a significant improvement in overall hematologic response.
Takeda discontinued a late-stage study that the Japanese pharma giant hoped would lead to a label-extension for its multiple myeloma drug, Ninlaro.
The company said Ninlaro (ixazomib) in combination with dexamethasone failed to demonstrate a significant improvement in overall hematologic response compared to standard of care in patients with relapsed or refractory systemic light-chain (AL) amyloidosis. Treatment with Ninlaro, an oral proteasome inhibitor, did not meet the first of two primary endpoints in the Phase III TOURMALINE-AL1 clinical trial, which was the hematological response. The second endpoint would have addressed organ failure. Phil Rowlands, head of Takeda’s Oncology Therapeutic Area Unit, said the company is disappointed with the failure and the Japan-based company aims to “maximize our learnings from this trial and share findings with the community in hopes of helping to improve care for patients living with this devastating disease.” He said the TOURMALINE-AL1 study is the largest ever conducted in systemic light-chain AL amyloidosis.
Primary AL amyloidosis is a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. The disorder causes misfolded immunoglobulin light chain protein to build up in and around tissues. That results in widespread organ damage, most commonly seen in the heart and kidneys. These misfolded light-chains form insoluble fibrils that aggregate as amyloid deposits in organs and tissues throughout the body, which damages and leads to death. There are currently no treatments approved for the treatment of AL amyloidosis. Patients with AL amyloidosis have a median survival time of less than 18 months following diagnosis. There are approximately 22,000 AL amyloidosis patients across the United States and parts of Europe. AL amyloidosis has a one-year mortality rate of 47 percent, 76 percent of which is caused by cardiac amyloidosis. Current standard of care includes plasma cell directed chemotherapy and autologous stem cell transplant.
While Ninlaro failed in this trial, Rowlands said the company remains confident about the efficacy the drug can have on disease. Takeda will continue to investigate Ninlaro in patient populations across the continuum of multiple myeloma care, Rowland said. Ninlaro was first approved by the U.S. Food and Drug Administration in November 2015 and is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.
The Phase III TOURMALINE-AL1 study was designed to determine whether Ninlaro in combination with dexamethasone improved hematologic response, two-year vital organ deterioration and mortality rate versus a physician’s choice of a chemotherapy regimen.
Although the Phase III was halted due to lack of efficacy, Takeda noted that an Independent Data Monitoring Committee (IDMC) did not raise any concerns about the safety profile of Ninlaro in this setting.
Takeda isn’t the only company focused on developing a treatment for light-chain (AL) amyloidosis. In January, Caelum Biosciences, a subsidiary of Fortress Biotech, and Alexion Pharmaceuticals forged an agreement to collaborate on the development of CAEL-101, a potential treatment for light chain (AL) amyloidosis.
