Meta-Analysis of VELCADE® (bortezomib)-Based Induction Therapy Followed by Stem-Cell Transplantation Showed Significantly

  Meta-Analysis of VELCADE® (bortezomib)-Based Induction Therapy Followed by
  Stem-Cell Transplantation Showed Significantly Greater Response and Longer
  Progression-Free and Overall Survival in Patients with Multiple Myeloma

    Complete Response and near complete response significantly higher with
 VELCADE-based induction across patient subgroups, including those with high
                              risk cytogenetics

Business Wire

CAMBRIDGE, Mass. -- April 7, 2013

Millennium: The Takeda Oncology Company with its parent company Takeda
Pharmaceutical Company Limited (TSE:4502) today announced data from a
meta-analysis of VELCADE-based regimens compared to non-VELCADE-based regimens
as induction therapy prior to autologous stem cell transplant (ASCT) in
patients with previously untreated multiple myeloma (MM). These data were
reported in an oral presentation at the 14^th International Myeloma Workshop
(IMW) held April 3-7, 2013 in Kyoto, Japan.

The median progression-free survival (PFS) was significantly higher with
VELCADE-based induction therapy compared to non-VELCADE-based: 35.9 months
compared to 28.6 percent respectively (p<0.0001), at a median follow up of 37
months. The post transplant combined complete response (CR) plus near-complete
response (nCR) rate, was 38 percent (n=298) compared to 24 percent (n=182)
percent respectively (p<0.0001), odds ratio of 2.05. Anodds ratio greater
than 1 indicatesthe increased odds apatient will achieve an endpoint with
one treatment over the odds of achieving that endpoint with a
comparator-treatment. In the meta-analysis VELCADE-based induction treatment
demonstrated a 23 percent overall survival benefit compare to
non-VELCADE-based induction treatment, HR 0.81 (CI: 0.66-0.99) (P=0.04).

“This meta-analysis demonstrated that VELCADE-based induction therapy improved
progression-free survival and overall survival in multiple myeloma patients
who underwent autologous transplantation,” said Karen Ferrante, M.D., Chief
Medical Officer, Millennium. “With data from more than 1,500 patients, this
meta-analysis underscores the extensive body of evidence, both in clinical
trials and real-world experience, that exists for VELCADE.”

Bortezomib-based versus non-bortezomib-based induction prior to ASCT in
multiple myeloma: meta-analysis of phase 3 trials (Abstract #O-11)

The primary objectives of this analysis were to compare the post-transplant
CR+nCR rates and PFS of VELCADE-based induction therapy (administered IV,
twice weekly) with non-VELCADE-based induction in previously untreated
patients with MM undergoing ASCT. Secondary endpoints included overall
response rate (ORR) and overall survival (OS). This meta-analysis of three
phase 3 studies included 1,572 patients. Results, which were presented by
Pieter Sonneveld, M.D., Dept. of Hematology, Erasmus Medical Center,
Rotterdam, the Netherlands, showed:

  *The integrated analysis, across these studies, reported the
    post-transplant CR+nCR for VELCADE-based regimens was 38 percent (n=298)
    compared to 24 percent (n=182) in non-VELCADE-based regimens (p<0.0001)
  *The median PFS was 35.9 months for VELCADE-based regimens compared to 28.6
    months for non-VELCADE-based regimens (p<0.0001)
  *The ORR, post-transplant, was 79 percent (n=615) for VELCADE-based
    regimens compared to 68 percent (n=526) for non-VELCADE-based regimens
    (p<0.0001)
  *After a median follow-up of 37 months, the three year OS rates were 79.7
    percent for VELCADE-based treatment compared to 74.7 percent for
    non-VELCADE-based treatment (HR 0.81 p=0.0402). Median OS has not been
    reached in either arm
  *Most common adverse events across the integrated analysis for
    VELCADE-based induction regimens compared to non-VELCADE-based induction,
    respectively, included; peripheral neuropathy (34 percent, 17 percent),
    constipation (31 percent, 28 percent) anemia (27 percent, 29 percent),
    nausea (28 percent, 27 percent), thrombocytopenia (31 percent, 22 percent)
    and leukopenia (25 percent, 27 percent)
  *Most common adverse events ≥Grade 3, VELCADE-based induction compared to
    non-VELCADE-based induction, respectively, included; leukopenia (14
    percent, 15 percent), anemia (7 percent, 10 percent), thrombocytopenia (8
    percent, 3 percent), peripheral neuropathy (6 percent, 1 percent),
    pneumonia (5 percent, 6 percent), neutropenia (4 percent, 6 percent),
    pyrexia (3 percent, 5 percent)

Patient-level data from three large phase 3 studies were pooled in a thorough
integrated analysis of efficacy and safety. Data from a fourth study was
included in a larger meta-analysis; however patient-level data was not
available due to legal restrictions and is not included in the data reported
here with the exception of the OS. The VELCADE-based regimens included VELCADE
(Vc) plus dexamethasone (dex), Vc plus doxorubicin plus dex and Vc plus
thalidomide (T) plus dex. Non-Vc-based regimens included vincristine plus
doxorubicin plus dex, and T plus dex.

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 400,000
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. VELCADE should not be administered intrathecally. Women should
avoid becoming pregnant or breastfeeding while taking VELCADE. Patients with
diabetes may require close monitoring and adjustment of their medication.

VELCADE can cause serious side effects, including:

  *Peripheral neuropathy. Nerve problems, which can be severe including
    muscle weakness, tingling, burning, pain, or loss of feeling in the hands
    and feet.
  *Low blood pressure.  A drop in blood pressure resulting in dizziness,
    light headedness or fainting.
  *Heart problems.  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 problems, some of which have been fatal. Symptoms include cough,
    shortness of breath, wheezing or difficulty breathing.
  *Liver problems.  Liver failure including a yellow discoloration of the
    eyes and skin.
  *Posterior reversible encephalopathy syndrome (PRES). a rare, reversible
    condition involving the brain. Symptoms may include seizures, high blood
    pressure, headaches, tiredness, confusion, blindness, or other vision
    problems
  *Gastrointestinal problems. Nausea, vomiting, diarrhea and constipation.
  *Thrombocytopenia and neutropenia. Lowering the levels of blood cells,
    which could result in a higher risk for infections or bleeding.
  *Tumor lysis syndrome (TLS). TLS  is a syndrome that causes a chemical
    imbalance in the blood that could lead to heart and/or kidney problems.

Common side effects seen in patients receiving VELCADE include: fever,
decreased appetite, fatigue, rash.

These are not all of the possible side effects with VELCADE. Please see the
full Prescribing Information for VELCADE for a complete list available at
VELCADE.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.

Contact:

Millennium
Manisha Pai, +1-617-551-7877
Manisha.pai@mpi.com
or
David Albaugh, +1-617-444-4456
david.albaugh@mpi.com
or
Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)
+81-3-3278-2037
 
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