-- First oral proteasome inhibitor to be investigated in amyloidosis --
--Trial conducted under Special Protocol Assessment (SPA) from US FDA--
CAMBRIDGE, Mass., October 19, 2012 -- Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today announced the initiation of an international phase 3 clinical trial evaluating once-weekly oral MLN9708 plus dexamethasone in patients with relapsed or refractory light chain AL amyloidosis. The multi-center study with MLN9708, an investigational oral proteasome inhibitor, plans to enroll patients in Europe, North America, Latin America and the Asia-Pacific region.
"Innovation is essential to the development of investigational therapies, especially in challenging orphan diseases such as amyloidosis," said Karen Ferrante, M.D., Chief Medical Officer, Millennium. "The MLN9708 amyloidosis trial employs a unique study design, including novel endpoints, developed by Millennium in collaboration with the FDA and the hematology community."
"There is a significant unmet medical need in the treatment of light chain amyloidosis, a rare and usually fatal disease," said Professor Giampaolo Merlini, MD, Amyloidosis Research and Treatment Center, University of Pavia, Italy. "There are currently no approved medications for light chain amyloidosis. This innovative study design may allow for earlier identification of clinical benefit for these very sick patients, and may establish a standard for future research in systemic amyloidosis."
The study known as TOURMALINE-AL1 is a prospective phase 3, randomized, controlled, open-label, multicenter study in patients with relapsed or refractory amyloidosis comparing once-weekly oral MLN9708 plus dexamethasone with investigator selected treatment. Patients in the treatment arm will receive MLN9708 (4.0 mg) orally on Days 1, 8, and 15 plus dexamethasone 20 mg/day weekly on Days 1, 8, 15, and 22 of each 28-day cycle; dexamethasone may be increased up to 40 mg/day after 4 weeks, if tolerated. Patients may continue to receive treatment until progressive disease or unacceptable toxicity, whichever comes first.
Patients in the comparator arm will receive one of the following 28-day treatment options as selected by the physician:
- Dexamethasone or, Dexamethasone plus melphalan or, Dexamethasone plus cyclophosphamide or, Dexamethasone plus thalidomide or, Dexamethasone plus lenalidomide.
The co-primary endpoints are overall hematologic response rate (ORR) including complete response (CR), very good partial response (VGPR), partial response (PR), and rate of 2-year vital organ deterioration and mortality rate. Secondary endpoints include safety, overall survival (OS), complete hematologic response CR, progression free survival (PFS), duration of response (DOR) and quality of life (QOL).
Primary AL amyloidosis occurs when the body's antibody-producing cells do not function properly and produce abnormal protein fibers known as amyloids. These amyloids can form deposits in any organ in the body. The most common organs affected are the kidney, heart, liver, and autonomic or peripheral nerves. The deposits can damage the affected organs and cause them to function less efficiently and may eventually lead to organ failure.
MLN9708 is an investigational oral, potent, proteasome inhibitor, which is being studied in multiple myeloma, various hematologic malignancies and solid tumors. It is the first oral proteasome inhibitor to enter clinical trials in patients. A global phase 3 trial, TOURMALINE-MM1, to investigate MLN9708 in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma has been initiated recently.
Editor's Note: This press release is also available under the Media section of the Company's website at: www.millennium.com/InTheNews.aspx.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company's research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)