-- 100 percent response rate achieved with VELCADE, lenalidomide and
dexamethasone --
KOS, Greece, June 28 /PRNewswire-FirstCall/ -- Millennium
Pharmaceuticals, Inc. (Nasdaq: MLNM) today reported on the presentation of
results from four clinical trials of VELCADE based therapies that showed
consistently high survival and complete remission / complete response(1)
(CR) rates in newly diagnosed multiple myeloma (MM) patients. These data
were presented at the prestigious 11th International Myeloma Workshop (IMW)
in Kos, Greece. Highlights included:
(Logo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )
-- VELCADE, melphalan and prednisone (VMP) demonstrated a CR(1) rate of
43 percent, the strongest rate ever reported for a melphalan
prednisone combination therapy. At 38 months, 85 percent of patients
were alive. This is the highest reported three-year survival rate in
the front-line treatment setting.
-- VELCADE, adriamycin and dexamethasone (referred to as VcAD or PAD)
showed a CR(1) rate of 29 percent prior to stem cell transplantation
(SCT), which further improved to 57 percent following SCT. At one
year, 100 percent of patients were alive, and at two years, 95 percent
of patients were alive. This is the highest reported two-year
survival rate in the front-line treatment setting. Median overall
survival (OS) has not yet been reached after four years.
-- VELCADE, DOXIL(R) (pegylated liposomal doxorubicin) and dexamethasone
(VDD) showed a CR(1) rate of 43 percent prior to SCT, which increased
to 65 percent following SCT. At 16 months, 100 percent of patients
were alive.
-- VELCADE, lenalidomide and dexamethasone (VRD) showed an overall
response rate (ORR) of 100 percent, including a CR(1) rate of 20
percent.
"These spectacular results underscore the crucial role of VELCADE in
front-line multiple myeloma," said Sagar Lonial, M.D., Emory University.
"VELCADE has consistently delivered survival rates that are among the
highest seen to date in this disease setting. These high survival rates
were driven by the substantial complete remission rates seen when VELCADE
has been added to multiple therapies. Oncologists generally use the most
efficacious agents as front-line treatment to maximize outcomes for
patients, and as such, VELCADE will be a leading therapy in this disease
setting."
Frontline VMP in Elderly Multiple Myeloma Patients: Extended Follow-Up
(Abstract #PO-718)
"The addition of VELCADE has produced the best complete remisssion and
three-year survival rates ever reported with a melphalan prednisone
therapy, providing results that are as powerful as stem cell
transplantation without the associated side effects, recovery time and
expense," said Maria-Victoria Mateos, M.D., Ph.D., Grupo Espanol de
Multiple Myeloma. "With VELCADE added to this combination, we now are able
to offer all patients, including those who historically could not have a
transplant, an alternative that provides complete remission and prolongs
lives."
The Phase I / II study evaluated efficacy and safety of VMP combination
therapy in untreated MM patients aged 65 years or older with a median age
of 75 years. The study included 54 evaluable patients ineligible for SCT.
Patients received VELCADE at 1.0 mg/m(2) or 1.3 mg/m(2) on days 1, 4, 8,
11, 22, 25, 29 and 32 for four six-week cycles, then on days 1, 8, 15 and
22 for five five-week cycles. Patients also received melphalan at 9 mg/m(2)
and prednisone at 60 mg/m(2) on days 1 through 4 of each cycle. Response
was assessed using the European Group for Blood and Marrow Transplant
(EBMT) criteria. Results were presented by Dr. Mateos and showed a CR rate
of 43 percent. At 38 months, 85 percent of patients were alive. Side
effects were predictable and manageable, similar to those seen in previous
VELCADE clinical trials.
Long Term Follow-Up of VcAD (or PAD) for Untreated Multiple Myeloma
(Abstract #PO-725)
The open-label Phase I / II study investigated the efficacy of VcAD
combination therapy in untreated MM patients. The trial included 40
evaluable patients, who were treated for four cycles prior to SCT. Patients
received either VELCADE at 1.3 mg/m(2) (VcAD-1) or 1.0 mg/m(2) (VcAD-2) on
days 1, 4, 8 and 11 of a 21-day schedule. Patients also received
doxorubicin at 9 mg/m(2) on days 1 through 4 and dexamethasone at 40 mg on
days 1 through 4, 8 through 11, and 15 through 18 during cycle one and on
days 1 through 4 during cycles two through four. Responses were classified
using the EBMT criteria. Results were presented by Rakesh Popat, M.D., St.
Bartholomew's Hospital, and showed in the VcAD-1 arm a CR rate of 29
percent prior to SCT, which improved to 57 percent following SCT. At one
year, 100 percent of patients were alive with 95 percent of patients alive
at two years. Median OS has not yet been reached after four years. Side
effects, including peripheral neuropathy, were predictable and manageable,
similar to those seen in previous VELCADE clinical trials.
Combination Therapy with VELCADE, DOXIL and Dexamethasone in Newly
Diagnosed Myeloma: Updated Results of a Phase II Clinical Trial (Abstract
#PO- 721)
The Phase II trial evaluated the efficacy of VDD combination therapy in
untreated MM patients. The trial enrolled 40 patients, who received VELCADE
at 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day schedule. Patients also
received DOXIL at 30 mg/m(2) on day 4 and dexamethasone at 40 mg on days 1
through 4 or 20 mg corresponding with the VELCADE schedule. After four
cycles of VDD, patients proceeded to SCT or continued VDD maintenance
therapy. Responses were determined based on the EBMT criteria. Results were
presented by Andrzej Jakubowiak, M.D., Ph.D., University of Michigan
Comprehensive Cancer Center, and demonstrated a CR rate of 43 percent prior
to SCT, which improved to 65 percent following SCT. At 16 months, 100
percent of patients were alive. Side effects were predictable and
manageable, similar to those seen in previous VELCADE clinical trials.
Phase I / II Study of Upfront VELCADE, Lenalidomide and Dexamethasone
in Multiple Myeloma: Early Results (Abstract #PO-715)
This Phase I / II study of VRD combination therapy was designed to
determine the maximum tolerated dose (MTD) and efficacy in untreated MM
patients. The preliminary analysis included 15 evaluable patients, who
received VELCADE at 1.0 mg/m(2) or 1.3 mg/m(2) on days 1, 4, 8 and 11 of a
21- day schedule. Patients also received lenalidomide at 15, 20 or 25 mg on
days 1 through 14 and dexamethasone at 40 mg corresponding with the VELCADE
schedule. Patients were treated for up to eight cycles at four planned dose
levels. MTD has not yet been reached. Response was assessed by modified
EBMT criteria. Results were presented by Paul Richardson, M.D., Dana-Farber
Cancer Institute, and showed an ORR (CR + partial response + minor
response) of 100 percent, including a CR rate of 20 percent. Side effects
were manageable and included hypophosphatemia, infections and
thrombocytopenia. No grade 3 or higher peripheral neuropathy was observed.
About Multiple Myeloma
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 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 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.
(1) Complete remission / complete response includes both immunofixation
positive and negative readouts
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 (857) 498-0818
SOURCE Millennium Pharmaceuticals, Inc.
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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, +1-617-444-1439,
Investors, Kyle Kuvalanka, +1-857-498-0818, both of Millennium
Pharmaceuticals, Inc.
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