- Positive data on subcutaneous administration show potential for new
option to improve convenience for patients -
- Recently FDA-approved VELCADE + DOXIL(R) (pegylated liposomal
doxorubicin) combination significantly extends time to disease progression
and is recognized as Best of ASCO -
CHICAGO, June 4 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals,
Inc. (Nasdaq: MLNM) today announced the presentation of positive data for
VELCADE, the market-leading therapy for patients with multiple myeloma (MM)
who have received at least one prior therapy. These data include results
from a Phase II trial for subcutaneous (SC) administration of VELCADE, a
new option under evaluation. Results were also presented from the
international Phase III trial of VELCADE + DOXIL, which served as the basis
for the recent U.S. approval of the combination and showed significant
improvement in time to disease progression compared to VELCADE alone, the
current standard of care. The VELCADE + DOXIL abstract was selected by the
Best of the American Society of Clinical Oncology (ASCO) Program Committee
as one of the premier abstracts at the 43rd Annual Meeting in Chicago.
(Logo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )
"We and our partner Johnson & Johnson Pharmaceutical Research and
Development L.L.C. continue to develop new clinical data that reinforce the
role of VELCADE as the U.S. market-leading therapy in previously treated
multiple myeloma," said Nancy Simonian, M.D., Chief Medical Officer,
Millennium. "These data demonstrate that VELCADE in combination with
another active agent can further strengthen the unparalleled impact of
VELCADE. We are aggressively pursuing development of a subcutaneous
delivery form to broaden alternatives for patients who prefer to receive
VELCADE treatment at home."
Prospective Comparison of Subcutaneous to Intravenous Administration of
Bortezomib in Patients with Multiple Myeloma: Pharmacokinetics, Efficacy
and Toxicity (Abstract #8046)
This randomized trial evaluated the pharmacokinetics/pharmacodynamics
(PK/PD), toxicity and response rate of VELCADE in patients treated with
either an SC or intravenous (IV) administration option. Results were
presented by Philippe Moreau, M.D., University Hospital Hotel-Dieu and
showed:
-- Similar bioavailability for the two routes of administration
-- Similar safety and tolerability profiles for the two routes of
administration with a trend favoring the SC route as evidenced by fewer
patients in this group discontinuing therapy
-- Identical response rates for the two routes of administration with both
groups of patients achieving an overall response rate (complete and
partial response) of 42 percent
The trial included 24 patients who were randomized to receive either SC
or IV injections of VELCADE at the standard dose of 1.3 mg/m2 twice weekly
for two weeks on days 1, 4, 8 and 11 with one week rest for up to eight
cycles. Blood samples were taken on days 1 and 11 to measure PK by plasma
Cmax (maximum plasma concentration), AUC (area under plasma
concentration-time curve) and Tmax (time to Cmax) values and to measure PD
by AUE (area under effect curve) and Emax (maximum effect) values. Patients
received a median number of six and five cycles in the IV and SC groups,
respectively.
Effect of the Combination of Pegylated Liposomal Doxorubicin and
Bortezomib on Time to Progression (TTP) and Overall Survival of Patients
With Relapsed/Refractory Multiple Myeloma Compared With Bortezomib Alone
(Abstract #8002)
"The combination of VELCADE + DOXIL is highly active, with the time to
disease progression the strongest in any U.S.-approved label for this
patient population," said Jean-Luc Harousseau, M.D., University Hospital
Hotel-Dieu. "Based on the Phase II trial, which showed a median overall
survival greater than 38 months, we believe that the strong efficacy of the
combination in the Phase III trial will extend to a substantial improvement
in overall survival as well."
The Phase III study compared the efficacy and safety of the combination
of VELCADE + DOXIL to VELCADE monotherapy, the standard of care in patients
with previously treated MM. Results were presented by Dr. Harousseau and
showed:
-- A survival advantage was observed for the VELCADE + DOXIL combination,
after approximately 20 percent of events occurred (p<0.05, hazard
ratio=1.406, 95 percent confidence interval [1.002; 1.972])
-- Median time to progression (TTP) of 9.3 months for the combination, a
43 percent, highly statistically significant reduction in risk of
disease progression over the control arm (p<0.00001)
-- A predictable safety profile consistent with the known toxicities of
the two agents, including thrombocytopenia, neutropenia and anemia
The trial included 646 patients who had received at least one prior
therapy. Patients were randomized in a one-to-one ratio, with 322 patients
receiving VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of the 21-day cycle
and 324 patients receiving the same dose and schedule of VELCADE with the
addition of DOXIL at 30 mg/m2 given on day 4 of each cycle. Patients were
treated for up to eight cycles. The primary endpoint of the study was TTP
as defined by the interval between the date of randomization and the date
of disease progression, including relapse after complete response or death
due to disease progression. In both arms, 66 percent of patients had
received more than two prior therapies before entering the trial. Responses
were assessed by European Group for Blood and Marrow Transplantation (EBMT)
criteria.
About Multiple Myeloma (MM)
Multiple myeloma is the second most common hematologic malignancy and
although the disease is predominantly a cancer of the elderly (the average
age of onset is 65 to 70 years of age), recent statistics indicate both
increasing incidence and younger age of onset. In the U.S., more than
50,000 individuals have MM and 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. will
co-promote VELCADE in the U.S. VELCADE is approved in more than 80
countries worldwide.
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, 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 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.
Safety Data: In 1163 patients in multiple myeloma and mantle cell
lymphoma studies, the most commonly reported adverse events were asthenic
conditions (64%), nausea (55%) in single-agent VELCADE, diarrhea (52%),
constipation (41%), peripheral neuropathy (39%), thrombocytopenia (36%),
appetite decrease, including reports of anorexia (36%), pyrexia (34%),
vomiting (33%) and anemia (29%). Twenty percent of patients reported at
least one episode of grade 4 toxicity; the most common grade 4 toxicities
were thrombocytopenia (5%) and neutropenia (3%). Fifty percent of patients
reported serious adverse events. The most commonly reported serious adverse
events were pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and
nausea, dehydration, dyspnea and thrombocytopenia (each 3%).
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.
Contacts:
Jennifer Snyder (media) Kyle Kuvalanka (investors)
(617) 448-0281 (857) 498-0818
SOURCE Millennium Pharmaceuticals, Inc.
 back to top
Related links:
http://www.millennium.com
Photo Notes:
NewsCom: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO
AP Archive: http://photoarchive.ap.org
PRN Photo Desk, photodesk@prnewswire.com
http://www.prnewswire.com/comp/114562.html /
CONTACT:
media, Jennifer Snyder, +1-617-448-0281, or
investors, Kyle Kuvalanka, +1-857-498-0818, both of Millennium
Pharmaceuticals, Inc.
|
