Data Reported From Phase 1 Study of Once a Week MLN9708 Oral Proteasome Inhibitor in Patients with Relapsed or Refractory Systemic Light-Chain Amyloidosis

Dec. 10, 2012

Investigational MLN9708: first oral proteasome inhibitor in amyloidosis

ATLANTA--(BUSINESS WIRE)-- Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today announced the presentation of data from a phase 1 study investigating once a week MLN9708 in patients with relapsed or refractory systemic light-chain (AL) amyloidosis. The primary objectives of this open-label, dose-escalation, phase 1 study were to determine the safety, tolerability, and maximum tolerated dose (MTD) of MLN9708 in patients with relapsed or refractory AL, and to determine the dose for future development. Once the MTD was reached, two expansion cohorts were enrolled, one with proteasome inhibitor-naïve patients (n=5) and one with proteasome inhibitor-exposed patients (n=12). The data were presented at the 54th American Society of Hematology (ASH) Annual Meeting and Exposition held December 8-11, 2012 in Atlanta, GA.

"Preliminary evidence of hematologic responses and early organ responses in this heavily pre-treated population are encouraging," said Karen Ferrante, M.D., Chief Medical Officer, Millennium. "The data from this study supports the on-going TOURMALINE-AL1 phase 3 trial of MLN9708 in patients with relapsed or refractory systemic light-chain amyloidosis."

MLN9708, a Novel, Investigational Oral Proteasome Inhibitor, in Patients with Relapsed or Refractory Light-Chain Amyloidosis (AL): Results of a Phase 1 Study (Abstract #731)

At data cut-off 22 patients had been enrolled: 17 at the MTD of 4.0 mg and 5 at 5.5 mg. Fifteen of 17 patients treated at the MTD were evaluable for response (received at least one cycle of treatment and had a response assessment). Results, which were presented by Professor Giampaolo Merlini, MD, Amyloidosis Research and Treatment Center, University of Pavia, Italy, showed:

  • The MTD and dose for future development was established as 4.0 mg
  • Two patients achieved a complete response (CR)
  • Five patients achieved a very good partial response (VGPR)
  • One patient achieved a partial response (PR)
  • Duration of hematological response of up to 14.7 months has been reported to date
  • There were 3 cardiac organ responses out of 9 evaluable patients
  • Three patients experienced disease progression by the end of cycle 1
  • Median number of cycles was 3 (range 1-12); eight patients remain on treatment
  • One patient in the 4.0 mg dose cohort had a dose-limiting toxicity (DLT) of grade 3 thrombocytopenia
  • The most common Grade 3/4 adverse events across all doses were thrombocytopenia (n=4), rash (n=3), diarrhea, asthenia/fatigue and dehydration (n=2), electrolyte imbalance, hypokalemia (occurred in the same patient) and cardiac arrest (n=1)

Patients with relapsed or refractory light-chain amyloidosis received escalating doses of oral MLN9708 on Days 1, 8 and 15 of a 28-day cycle. If there was no hematologic response after completion of 3 cycles, dexamethasone was added on Days 1 to 4 of every cycle beginning with cycle 4. If there was no hematologic response after the completion of 6 cycles, patients would discontinue therapy. Hematological response and amyloid-related organ assessments were performed according to standardized criteria.

About Amyloidosis

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.

About MLN9708

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. Two global phase 3 trials, TOURMALINE-MM1, to investigate MLN9708 in combination with lenalidomide and dexamethasone in relapsed and/or refractory multiple myeloma and TOURMALINE-AL1, to investigate MLN9708 plus dexamethasone in patients with relapsed or refractory light chain AL amyloidosis were initiated in 2012. For additional information on the ongoing phase 3 studies please visit www.tourmalinetrialal1.com and www.tourmalinetrialmm1.com

Editor's Note: This press release is also available under the Media section of the Company's website at: www.millennium.com/InTheNews.aspx.

About Millennium

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.

About Takeda

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.


Manisha Pai, +1-617-551-7877
David Albaugh, +1-617-444-4456
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)
Tel: +81-3-3278-2037

Source: Millennium: The Takeda Oncology Company

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