MLN8237 in Phase 2 Clinical Trial featured in best of ASH presentation
CAMBRIDGE, Mass., December 19, 2011 – Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today reported the presentation of results from a phase 2 trial evaluating MLN8237, an investigational inhibitor of Aurora A kinase, in patients with aggressive B- and T-Cell non-Hodgkin lymphoma (NHL). Also presented were biomarker data from a phase 3 study comparing VELCADE® (bortezomib) and rituximab (VcR) to rituximab (R) alone in patients with relapsed or refractory follicular lymphoma (FL). These data were presented during oral presentations at the 53rd annual meeting of the American Society of Hematology (ASH), held December 10th – 13th in San Diego, California.

“At Millennium we are dedicated to researching the role of biomarkers in patient selection in lymphoma,” said Karen Ferrante, M.D., Chief Medical Officer, Millennium.

MLN8237 was the subject of three presentations at ASH 2011, including an oral presentation of a phase 2 trial evaluating MLN8237 in patients with relapsed/refractory aggressive B- and T-Cell NHL. The data were presented by Jonathan Friedberg, M.D., James P. Wilmot Cancer Center, University of Rochester, Rochester, NY.

The results from this study of VELCADE were derived from an exploratory biomarker sub-analysis of the large phase III randomized trial known as LYM-3001. These data were presented by Bertrand Coiffier, M.D., Hospices Civils de Lyon, Hematology, Pierre-Benite, France.

Multicenter Phase 2 Trial of MLN8237, an Investigational Inhibitor of Aurora A Kinase, in Patients with Aggressive B-cell and T-cell NHL (Abstract # 95)

This study evaluated the efficacy, safety and tolerability of MLN8237 in 48 patients with relapsed/refractory aggressive B-cell or T-cell NHL.

• The overall response rate (ORR) was 32% (95% CI 18%–48%)
• Of the 41 evaluable patients, the following number of patients, by histology, responded:
o Diffuse large B-cell lymphoma (DLBCL), n=3 (20%),
o mantle cell lymphoma (MCL), n=3 (23%), and
o peripheral T-cell lymphoma n=4 (57%),
o Burkitt’s lymphoma n= 1 (100%)
o Transformed follicular lymphoma n=2 (40%)
• Most common Grade 3/4 adverse events were neutropenia n=30 (63%), 7 of which were febrile neutropenia, thrombocytopenia n=15 (31%), stomatitis n=7 (15%), and fatigue n=3 (6%)
• Four patients died on study during cycle one, 2 of progressive DLBCL, 1 of sepsis and 1 sudden death, cause unknown
The study enrolled 48 patients, including 41 who were response-evaluable. Histologies included DLBCL (n=21, 44%), MCL (n=13, 27%), peripheral T- cell (n=8, 17%), transformed follicular (n=5, 10%) and Burkitt (n=1, 2%). Patients were treated with MLN8237 at a dose of 50mg twice daily for 7 days on 21 day cycles until either documented progression or unacceptable treatment-related toxicity. Two planned trials testing MLN8237 in relapsed/refractory PTCL: a planned, randomized global phase 3 trial and a phase 2 trial sponsored by SWOG.A phase 1-2 trial in DLBCL is currently enrolling patients.

Identification of Patient Subgroups Demonstrating Longer Progression-Free Survival (PFS) Benefit with Bortezomib-Rituximab Versus Rituximab in Patients with Relapsed or Refractory Follicular Lymphoma (FL): Biomarker Analyses of the Phase 3 LYM3001 Study (Abstract #265)

This post-hoc exploratory analysis showed:

• The biomarker pair of PSMB1 P11A C/G heterozygote and low CD68 expression was associated with a significantly longer median progression free survival (PFS) of 16.6 months in patients receiving VcR compared to 9.1 months for patients receiving R alone (HR=0.407, p<0.0001)
• The biomarker pair of PSMB1 P11A C/G heterozygote had a population frequency of 118 (33%) in 356 biomarker evaluable patients
• There was a significantly longer time to next therapy (TTNT) (median 33.1 vs. 14.8 months, p=0.0013) in patients with this biomarker pair receiving VcR compared to R alone
The randomized, international, phase 3 LYM3001 study enrolled 676 patients from 164 centers in 29 countries globally. 1140 pair-wise comparisons were analyzed in 356 patients with 14 identified pairs that showed differences in median PFS. The PFS difference remained significant for one biomarker pair PSMB1 P11A C/G heterozygote and low CD68. The data on primary and secondary endpoints were previously reported at ASH 2010.

About VELCADE
VELCADE is co-developed by Millennium and Janssen Pharmaceutical Companies. Millennium is responsible for commercialization of VELCADE in the U.S.; Janssen Pharmaceutical Companies are responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote VELCADE in Japan. VELCADE is approved in more than 90 countries and has been used to treat more than 300,000 patients worldwide.

Important Safety Information

VELCADE® (bortezomib) is approved for the treatment of patients with multiple myeloma. VELCADE is also approved for the treatment of patients with mantle cell lymphoma who have already received at least one prior treatment.

Patients should not receive VELCADE if they are allergic to bortezomib, boron or mannitol. Women should be advised not to take VELCADE while pregnant or breast-feeding. Patients with diabetes may require close monitoring and adjustment of their medication.

VELCADE can cause serious side effects, including:

• Lowering the levels of blood cells, which could result in a higher risk for infections or bleeding.
• Nausea, vomiting, diarrhea and constipation.
• Nerve problems, which can be severe including muscle weakness, tingling, burning, pain, or loss of feeling in the hands and feet.
• A drop in blood pressure resulting in dizziness, light headedness or fainting.
• Heart rhythm problems and heart failure including worsening of existing conditions. Symptoms may include chest pressure or pain, palpitations, swelling of the ankles or feet, or shortness of breath.
• Lung disorders, some of which have been fatal. Symptoms include cough, shortness of breath, wheezing or difficulty breathing.
• Liver failure including a yellow discoloration of the eyes and skin.
• Tumor Lysis Syndrome and Reversible Posterior Leukoencephalopathy Syndrome have been reported.
Common side effects seen in patients receiving VELCADE include: fever, decreased appetite, fatigue, insomnia and headache.

Additional information and full prescribing information is available at www.VELCADE.com.
Please see the full prescribing information for VELCADE including warnings and precautions.

For more information about VELCADE clinical trials, patients and physicians can contact the Millennium Medical Product Information Department at 1-866-VELCADE (1-866-835-2233).

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