-- Trial results of combination therapy VELCADE, melphalan and prednisone
reported a 32 percent complete remission rate with 85 percent of patients
alive at three years --
CAMBRIDGE, Mass., March 13 /PRNewswire-FirstCall/ -- Millennium
Pharmaceuticals, Inc. (Nasdaq: MLNM) today announced the publication of
updated results of the Phase I/II clinical trial of the combination therapy
VELCADE, melphalan and prednisone (VcMP) in newly diagnosed multiple
myeloma patients, who were ineligible for stem cell transplantation.
Results of this study included one of the highest reported complete
remission (CR) rates, which is an important indicator for long-term
survival, and the highest three- year survival rate reported in the
non-transplant setting. These results provided the basis for the Phase III
VISTA trial. The Company submitted a supplemental New Drug Application
(sNDA) to the U.S. Food and Drug Administration (FDA) in December 2007 for
VELCADE expansion into newly diagnosed multiple myeloma. The FDA decision
date for the sNDA is scheduled for June 20, 2008. The Company's
co-development partner, Johnson & Johnson Pharmaceutical Research &
Development, L.L.C. (J&JPRD) also has filed a corresponding application
with the European Medicines Evaluation Agency.
(Logo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )
"These results support the strong relationship between high rates of
durable complete remissions with long-term survival in patients with newly
diagnosed multiple myeloma," said Nancy Simonian, M.D., Chief Medical
Officer, Millennium. "We are confident that VELCADE will be a key component
of the standard of care in this patient setting."
The study was pre-published online in the journal, Haematologica. Data
from the 60 patient Phase I/II trial conducted by the PETHEMA Foundation in
Spain were evaluated by the stringent European Group for Blood and Marrow
Transplantation (EBMT) criteria and results are as follows:
-- Results showed an immunofixation-negative CR rate of 32 percent and an
overall response rate (ORR) of 89 percent with VcMP.
-- The overall survival rate at 38 months was 85 percent with VcMP
compared to the 38 percent historical control with melphalan and
prednisone (MP) (p<0.0001). The median overall survival for VcMP has
not been reached compared to 26 months among the historical control
with MP.
-- The median time-to-disease progression (TTP) with VcMP of 27.2 months
compared to 20 months for the historical control with MP (p=0.001).
-- The median event-free survival (EFS) with VcMP of 25 months compared to
15 months for the historical control with MP (p=0.001).
-- VcMP was well tolerated in this elderly patient population (median age
of 75) with patients on therapy for more than nine months. The safety
profile was predictable and manageable.
Patients received VELCADE at 1.3 mg/m2 (n=54) or 1.0 mg/m2 (n=6) twice
weekly in weeks one, two, four and five for four six-week cycles (eight
doses per cycle), followed by once weekly in weeks one, two, three and four
for five, five-week cycles (four doses per cycle) in combination with
melphalan at 9 mg/m2 and prednisone at 60 mg/m2 once daily on days 1
through 4 of each cycle. Treatment continued for a maximum of 49 weeks (52
vials) with a median number of 39 weeks (42 vials) reported in the trial.
The safety profile of VcMP was as expected based on the known safety
profile of each of the individual agents in the combination, including
thrombocytopenia, neutropenia and peripheral neuropathy.
About Multiple Myeloma
Multiple myeloma is the second most common hematological malignancy and
although the disease is predominantly a cancer of the elderly (the median
age of onset is 70 years of age), recent statistics indicate both
increasing incidence and younger age of onset. In the U.S., more than
55,000 individuals have multiple myeloma and approximately 20,000 new cases
are diagnosed each year. Worldwide there are approximately 74,000 new cases
and over 45,000 deaths annually.
About VELCADE
VELCADE is being co-developed by Millennium Pharmaceuticals, Inc. and
Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium
is responsible for commercialization of VELCADE in the U.S. and
Janssen-Cilag is responsible for commercialization in Europe and the rest
of the world. Janssen Pharmaceutical K.K. is responsible for
commercialization in Japan. For a limited period of time, Millennium and
Ortho Biotech Inc. are co- promoting VELCADE in the U.S. VELCADE is
approved in 85 countries worldwide. More than 85,000 patients have been
treated with VELCADE globally.
In the U.S., VELCADE is indicated for the treatment of patients with
multiple myeloma who have received at least one prior therapy. VELCADE is
also indicated for the treatment of patients with mantle cell lymphoma who
have received at least one prior therapy. VELCADE is contraindicated in
patients with hypersensitivity to bortezomib, boron, or mannitol. VELCADE
should be administered under the supervision of a physician experienced in
the use of antineoplastic therapy. In the European Union and many other
countries worldwide, VELCADE is approved for patients with multiple myeloma
after first relapse.
Risks associated with VELCADE therapy include new or worsening
peripheral neuropathy, hypotension observed throughout therapy, cardiac and
pulmonary disorders, gastrointestinal adverse events, thrombocytopenia,
neutropenia and tumor lysis syndrome. Women of childbearing potential
should avoid becoming pregnant while being treated with VELCADE. Cases of
severe sensory and motor peripheral neuropathy have been reported. The
long-term outcome of peripheral neuropathy has not been studied in mantle
cell lymphoma. Acute development or exacerbation of congestive heart
failure, and/or new onset of decreased left ventricular ejection fraction
has been reported, including reports in patients with few or no risk
factors for decreased left ventricular ejection fraction. There have been
rare reports of acute diffuse infiltrative pulmonary disease of unknown
etiology such as pneumonitis, interstitial pneumonia, lung infiltration and
Acute Respiratory Distress Syndrome in patients receiving VELCADE. Some of
these events have been fatal. A higher proportion of these events have been
reported in Japan. There have been rare reports of Reversible Posterior
Leukoencephalopathy Syndrome (RPLS) in patients receiving VELCADE. RPLS is
a rare, reversible, neurological disorder which can present with seizure,
hypertension, headache, lethargy, confusion, blindness, and other visual
and neurological disturbances. VELCADE is associated with thrombocytopenia
and neutropenia. There have been reports of gastrointestinal and
intracerebral hemorrhage in association with VELCADE. Transfusions may be
considered. Complete blood counts (CBC) should be frequently monitored
during treatment with VELCADE. Rare cases of acute liver failure have been
reported in patients receiving multiple concomitant medications and with
serious underlying medical conditions.
Integrated Safety Data: Safety data from Phase II and III studies of
single-agent VELCADE 1.3 mg/m2/dose twice weekly for 2 weeks followed by a
10- day rest period in 1163 patients with multiple myeloma (N=1008) and
mantle cell lymphoma (N=155) were integrated and tabulated. In these
studies, the safety profile of VELCADE was similar in patients with
multiple myeloma and mantle cell lymphoma. In the integrated analysis, the
most commonly reported adverse events were asthenic conditions (including
fatigue, malaise, and weakness) (64%), nausea (55%), diarrhea (52%),
constipation (41%), peripheral neuropathy NEC (including peripheral sensory
neuropathy and peripheral neuropathy aggravated) (39%), thrombocytopenia
and appetite decreased (including anorexia) (each 36%), pyrexia (34%),
vomiting (33%), and anemia (29%). Twenty percent (20%) of patients
experienced at least 1 episode of >/= Grade 4 toxicity, most commonly
thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients
experienced serious adverse events (SAEs) during the studies. The most
commonly reported SAEs included pneumonia (7%), pyrexia (6%), diarrhea
(5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia
(each 3%). Adverse events thought by the investigator to be drug-related
and leading to discontinuation occurred in 22% of patients. The reasons for
discontinuation included peripheral neuropathy (8%), asthenic conditions
(3%) and thrombocytopenia and diarrhea (each 2%). In total, 2% of the
patients died and the cause of death was considered by the investigator to
be possibly related to study drug: including reports of cardiac arrest,
congestive heart failure, respiratory failure, renal failure, pneumonia and
sepsis. This integrated analysis does not include the Phase III, VELCADE
plus DOXIL study.
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).
About Millennium
Millennium Pharmaceuticals, Inc., a leading biopharmaceutical company
based in Cambridge, Mass., markets VELCADE, a novel cancer product, and has
a robust clinical development pipeline of product candidates. Millennium's
research, development and commercialization activities are focused in two
therapeutic areas: oncology and inflammation. By applying its knowledge of
the human genome, understanding of disease mechanisms and industrialized
drug discovery platform, Millennium is developing an exciting pipeline of
innovative product candidates. Millennium's website is http://www.millennium.com.
This press release contains "forward-looking statements," including
statements about the Company's growth and development of products. Various
important risks may cause the Company's actual results to differ materially
from the results indicated by these forward-looking statements, including:
adverse results in its drug discovery and clinical development programs;
failure to obtain patent protection for its discoveries; commercial
limitations imposed by patents owned or controlled by third parties; the
Company's dependence upon strategic alliance partners to develop and
commercialize products and services based on its work; difficulties or
delays in obtaining regulatory approvals to market products and services
resulting from its development efforts; product withdrawals; competitive
factors; difficulties or delays in manufacturing the Company's products;
government and third-party reimbursement rates; the commercial success of
VELCADE and INTEGRILIN(R) (eptifibatide) Injection; achieving revenue
consistent with internal forecasts; and the requirement for substantial
funding to conduct research and development and to expand commercialization
activities. For a further list and description of the risks and
uncertainties the Company faces, see the reports it has filed with the
Securities and Exchange Commission. The Company disclaims any intention or
obligation to update or revise any forward- looking statements, whether as
a result of new information, future events or otherwise.
Editors' Note: This press release is also available under the Media
section of the Company's website at: http://www.millennium.com
Contacts:
Jennifer Snyder (media) Kyle Kuvalanka (investors)
(617) 444-1439 (617) 761-4734
SOURCE Millennium Pharmaceuticals, Inc.
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Related links:
http://www.millennium.com
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CONTACT:
Media: Jennifer Snyder, +1-617-444-1439;
Investors: Kyle Kuvalanka, +1-617-761-4734, both for Millennium
Pharmaceuticals, Inc.
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