- Phase II trials report high overall response rates in relapsed patients -
ORLANDO, Fla., Dec. 11 /PRNewswire-FirstCall/ -- Millennium
Pharmaceuticals, Inc. (Nasdaq: MLNM) today reported overall response rates
(ORR) as high as 75 percent from Phase II clinical trials of VELCADE(R)
(bortezomib) for Injection combination therapy across four subtypes of
non-Hodgkin's lymphoma (NHL): follicular, marginal zone, mantle cell
lymphoma (MCL) and T-cell lymphoma. These data include positive results
from the Phase II study of VELCADE in combination with rituximab in
follicular lymphoma, which served as the basis for an ongoing Phase III
registration-enabling trial initiated earlier this year. The findings were
presented at the 48th Annual Meeting of the American Society of Hematology
(ASH) being held December 9-12, 2006, in Orlando, Fla.
(Logo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO )
"These results build on the strong single-agent activity previously
seen with VELCADE in NHL and represent a significant step forward in
accelerating and expanding the development of VELCADE in combination for
the treatment of a variety of lymphomas," said Andy Boral, M.D., Ph.D.,
Senior Medical Director, Millennium. "Our recent approval in MCL
demonstrates the ability of VELCADE to provide significant benefit to
patients, even with the most aggressive types of lymphoma, and may lead to
the establishment of a new standard of care."
VELCADE received full approval from the U.S. Food and Drug
Administration (FDA) on December 8, 2006 for treatment of patients with MCL
who have received at least one prior therapy, marking the first indication
for VELCADE in lymphoma and the first therapy to receive FDA approval in
this treatment setting.
Phase II Study of VELCADE (Bortezomib) Weekly or Twice Weekly Plus
Rituximab in Patients with Follicular or Marginal Zone Lymphoma: Final
Results (Abstract #694)
The multicenter Phase II study evaluated the safety and efficacy of
VELCADE in combination with rituximab in 81 patients with follicular or
marginal zone lymphoma. Response was evaluated by independent radiology
review and by investigator assessment using the International Workshop
Response Criteria (IWRC). Patients were randomized to receive either four
weekly VELCADE doses at 1.6 mg/m2 on a 35-day cycle or twice-weekly VELCADE
at 1.3 mg/m2 on a 21-day cycle. All patients received weekly rituximab at
its regular weekly dose of 375 mg/m2 for four weeks. Patients were treated
for a maximum of three cycles in the weekly VELCADE arm and five cycles in
the twice-weekly VELCADE arm. The data were presented by Sven de Vos, M.D.,
Ph.D., of UCLA Medical Center in Los Angeles, Calif. Final results showed:
* By investigator assessment using the IWRC:
-- ORR (complete response [CR], complete response unconfirmed [CRu] and
partial response [PR]) was 53 percent among patients treated with
once-weekly VELCADE and 57 percent among patients treated in the
twice-weekly arm
-- Median time to progression (TTP) was nine months among patients
treated with once- weekly VELCADE and 9.9 months among patients
treated with twice-weekly VELCADE
* By independent radiology review:
-- ORR was 38 percent among patients treated with weekly VELCADE and 46
percent treated with twice-weekly VELCADE
-- Median TTP was 9.7 months among patients treated with VELCADE weekly
and 5.2 months among patients treated with VELCADE twice-weekly
* The total amount of VELCADE received was similar in both arms
* Therapy was well tolerated; the most common adverse events with both
weekly and twice-weekly VELCADE were fatigue, gastrointestinal events
and peripheral neuropathy
* The weekly dosing schedule was determined to have similar efficacy to
the twice-weekly schedule with the additional benefits of fewer grade 3
and 4 toxicities and a more convenient dosing schedule
* Based on these results, a randomized Phase III trial of VELCADE in
combination with rituximab compared to rituximab alone was initiated
earlier this year under a Special Protocol Assessment with the FDA
Marked Activity of VELCADE (Bortezomib), Rituximab and Dexamethasone in
Relapsed and Refractory Mantle Cell Lymphoma (Abstract #2753)
The single-arm Phase II study evaluated the efficacy and safety of
VELCADE in combination with rituximab and dexamethasone in 12 evaluable
patients with relapsed MCL. VELCADE at 1.3 mg/m2 was administered on days
1, 4, 8 and 11, rituximab at 375 mg/m2 was administered on day 1, and oral
dexamethasone at 40 mg was administered on days one through four. Cycles
were repeated every three-weeks for six cycles. The study was presented by
Johannes Drach, M.D., of the Medical University of Vienna, Austria. Results
showed:
* ORR was 75 percent with 25 percent of patients achieving a CR
* All patients who achieved CR were progression free at 12 months
* Therapy was well tolerated; the most common adverse events included
infections, peripheral neuropathy and fatigue
Phase II Study of Proteasome Inhibitor VELCADE (Bortezomib) in Patients
with Relapsed/Refractory T-cell Lymphoma: Preliminary Results (Abstract
#2462)
The Phase II study evaluated the efficacy and safety of single-agent
VELCADE in 12 evaluable previously treated patients with peripheral T-cell
lymphoma. Response was assessed using the National Cancer Institute Working
Group criteria. VELCADE was administered at 1.3 mg/m2 on days 1, 4, 8 and
11 during a 21-day cycle for up to six cycles. The study was led by Pier
Luigi Zinzani, M.D., Unit of Cardiology and Hematology, Institute of
Hematology and Medical Oncology, University of Bologna, Bologna, Italy.
Interim results showed:
* ORR was 67 percent including 17 percent of patients achieving a CR
* Treatment was well tolerated; the most frequent adverse events were
neutropenia, thrombocytopenia and peripheral neuropathy
About Non-Hodgkin's Lymphoma
Non-Hodgkin's lymphoma (NHL) is the most common hematological cancer,
the fifth leading cause of cancer death and the second fastest growing form
of cancer in the U.S.(1) The prevalence of NHL is approximately 400,000
patients, 77,000 patients with follicular lymphoma and 10,000 with mantle
cell lymphoma. There are approximately 54,000 new cases of NHL diagnosed
per year, and 19,000 deaths are attributed to the disease annually(2,3).
Mantle cell lymphoma is an aggressive, rapidly progressive subtype of
NHL, and is not curable with standard treatment. Because there is no
generally accepted treatment approach and options often are limited, there
is a growing need for new therapies. The average life expectancy for a
patient with relapsed mantle cell lymphoma is one year.
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 also is approved in the European
Union after first relapse.
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.
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 (ARDS) 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 MM and MCL studies, the most commonly
reported adverse events were asthenic conditions (64%), nausea (55%),
diarrhea (52%), constipation (41%), peripheral neuropathy (39%),
thrombocytopenia (36%), appetite decreased, 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 (SAEs). The most
commonly reported SAEs 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. The Company'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. The Company'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.
1. 2005, American Cancer Society, Inc., Surveillance Research.
2. SEER, SARGA, and Decision Resources (for growth rate) data.
3. Federico et al., BLOOD 95(3): 783-789; 2000.
Contacts:
Jennifer Snyder (media) Kyle Kuvalanka (investors)
(617) 448-0281 (857) 498-0818
SOURCE Millennium Pharmaceuticals, Inc.
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http://www.millennium.com/
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CONTACT:
Media, Jennifer Snyder +1-617-448-0281, or
Investors, Kyle Kuvalanka, +1-857-498-0818, both for Millennium
Pharmaceuticals, Inc.
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