Millennium
Pharmaceuticals, Inc. (Nasdaq: MLNM) announced the submission of a
supplemental new drug application (sNDA) with the U.S. Food and Drug
Administration (FDA) for VELCADE in the treatment of patients with
previously untreated multiple myeloma (MM). The filing is based on data
from the 682 patient Phase III VISTA(1) trial, one of the largest,
international, randomized clinical trials for patients in this treatment
setting. Janssen- Cilag International NV also submitted a Marketing
Authorization Application to the European Medicines Evaluations Agency.
The VISTA trial compared VELCADE, melphalan and prednisone (VcMP) to
the standard regimen of melphalan and prednisone (MP) alone. For the VcMP
treatment, there was a statistically significant improvement in all
efficacy endpoints, including complete remission (CR) rates,
time-to-disease progression (TTP) and survival.
"This submission is an important step in expanding the benefits of
VELCADE therapy from patients with relapsed disease to those with
previously untreated multiple myeloma. We will request a priority review
and, if granted, we could expect approval by mid-2008," said Deborah
Dunsire, M.D., President and Chief Executive Officer, Millennium.
(1) VELCADE as Initial Standard Therapy in multiple myeloma: Assessment
with melphalan and prednisone
About Multiple Myeloma
Multiple myeloma is the second most common hematologic 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 MM 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., 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. currently
co-promote 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
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 2 and 3 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 greater than or equal to 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 3, VELCADE plus DOXIL study.
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 millennium.
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.
Millennium Pharmaceuticals, Inc.
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