News R
elease
FOR RELEASE JANUARY 23, 2012
FDA Approves Subcutaneous Administration of VELCADE® In All Approved Indications
Study met primary efficacy endpoint of non-inferiority between subcutaneous and intravenous
administration
Study results also indicated overall similar safety profile w
with differences in incidence of peripheral
neuropathy
CAMBRIDGE, Mass., January 23, 2012Millennium: The Takeda Oncology Company with its parent
company Takeda Pharmaceutical Company Limited (TSE:4502) today announced that the U.S. Food and
Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for
VELCADE®(bortezomib), which updates the label to include the subcutaneeous method of administration
in all approved indications: multiple myeloma and mantle cell lymphoma after at least one prior therapy.
The approval was based on results from a randomized, phase 3, open-labell, international, non-inferiority
trial conducted in 222 bortezomib-naïve patients with relapsed multiple myeloma (MM). The primary
(non-inferiority) objective of the trial was to demonstrate that single agent subcutaneous VELCADE
retained at least 60 percent of the overall response rate (ORR) after 4 cycles relative to single agent
intravenous VELCADE. Patients in both arms who did not obtain an optimal response (less than complete
response (CR)) to therapy with VELCADE alone after 4 cycles were allowed to receive 20 mg of oral
dexamethasone daily on the day of and after VELCADE administration. The secondary endpoints of the
study included safety and tolerability, ORR and CR rate after 8 cycles, time to progression (TTP),
progression free survival (PFS), and one-year overall survival (OS) of the two routes of administration.
Subcutaneous Administration
The pivotal study, published in the Lancet Oncology in May 2011, met its primary efficacy endpointt.
Patients receiving VELCADE subcutaneously achieved a 4-cycle ORR of 43 percent and CR rate of 7
percent, while patients receiving VELCADE intravenously achieved an ORR of 42 percent and a CR rate
of 8 percent. The overall safety profile was similar between the two arms. However, differences were
observed in the incidence of peripheral neuropathy (PN). In the subcutaneous arm of the trial, 6 percent of
patients experienced PN of grade 3 or higher, compared with 16 percent in the intravenous arm. In the
subcutaneous arm, 38 percent of patients experienced PN of all grades, compared with 53 percent of
patients in the intravenous arm.
"Subcutaneous VELCADE is yet another advance in the management of patients with multiple myeloma
or relapsed mantle cell lymphoma," said Karen Ferrante, M.D., Chief Medical Officer, Millennium. "The
consistency in efficacy findings, and observed differences in peripheral neuropathy, allow physicians to
tailor VELCADE treatment for their patients."
"Considering this new subcutaneous route of administration for VELCADE is important for our patients,
including those with poor vein access and those with pre-existing peripheral neuropathy or a high risk of
developing peripheral neuropathy," said Noopur Raje, M.D. director of the Center for Multiple Myeloma
at Massachusetts General Hospital Cancer Center. "It's important to have a range of treatment options to
provide the best possible care to each individual patient."
Additional study results at 8 cycles of treatment for subcutaneous and intravenous VELCADE,
respectively, included:
ORR 53 percent and 51 percent
CR rate 11 percent and 12 percent
Additional study results at 11.8-month median follow-up for subcutaneous and intravenous VELCADE,
respectively, included:
TTP 10.4 months and 9.4 months
PFS 10.2 months and 8.0 months
OS at 1 year 72.6 percent and 76.7 percent
Grade 3 and above adverse events with differences greater than 5 percent between routes of
administration were:
Peripheral neuropathy, subcutaneous 6 percent, intravenous 16 percent
Thrombocytopenia, subcutaneous 13 percent, intravenous 19 percent
Neuralgia, subcutaneous 3 percent, intravenous 9 percent
New Contraindication for Intrathecal Administration
The updated label also includes a contraindication for intrathecal administration as fatal events have
occurred with the inadvertent intrathecal administration of VELCADE. VELCADE is for intravenous or
subcutaneous use only.
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. VELCADE
should not be administered intrathecally. 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:
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.
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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.
Nausea, vomiting, diarrhea and constipation.
Lowering the levels of blood cells, which could result in a higher risk for infections or
bleeding.
Tumor lysis syndrome and reversible posterior leukoencephalopathy syndrome have been
reported.
Liver failure including a yellow discoloration of the eyes and skin.
Common side effects seen in patients receiving VELCADE include: fever, decreased appetite, fatigue,
insomnia and headache.
These are not all of the possible side effects with VELCADE. Please see the full Prescribing Information
for VELCADE for a complete list also available at www.VELCADE.com.
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).
# # #
Editors' 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 biopharmaceuticaal 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-baased global company with its main focus on
pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of th
he
industry, Takeda is committed to strive towards better health for patients worldwide thro
ough leading
innovation in medicine. Additional information about Takeda is available through its corporate website,
www.takeda.com.
Contacts:
Millenniu
um: The Takeda Oncology Company
Manisha Pai
+1-617-551-7877
manisha.pai@mpi.com
David Albaugh
+1-617-444-4456
david.albaugh@mpi.com
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Takeda Pharmaceutical Company Limited
Corporate Communications Dept. (PR/IR)
Tel: +81-3-3278-2037
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