Multiple Clinical Trials of VELCADE(R) (Bortezomib) for Injection Based
Therapies Demonstrate High Complete Remission Rates in Patients with Newly
Diagnosed Multiple Myeloma
CHICAGO, May 31 /PRNewswire/ -- Millennium Pharmaceuticals, The Takeda
Oncology Company, today announced the presentation of results from three
clinical trials of VELCADE based therapies that showed consistently high
complete remission(1) (CR) rates in patients with newly diagnosed multiple
myeloma (MM). CR is one of the best predictors of long-term survival. These
three studies were selected for oral presentation at the American Society of
Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, May 30 - June 3,
2008. Highlights included:
-- VELCADE, cyclophosphamide, and dexamethasone (CyBorD) demonstrated a
CR rate of 46 percent prior to transplant and 72 percent
post-transplant
-- VELCADE, DOXIL and dexamethasone (PAD or VcDD) prior to transplant
showed a CR rate of 21 percent which increased to 59 percent
post-transplant
-- VELCADE, lenalidomide and dexamethasone (VRD) showed a CR rate of 35
percent at maximum planned dose and a 100 percent overall response
rate.
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"The goal of first-line therapy is to rapidly achieve the deepest and most
durable response possible," said Nancy Simonian, M.D., Chief Medical Officer,
Millennium. "VELCADE based combinations produce among the highest CR rates
that are similar to those achieved by high dose therapy and transplantation.
These very strong results underscore the critical role of VELCADE in patients
with newly diagnosed multiple myeloma."
Efficacy of Induction with CyBorD in Newly Diagnosed Multiple Myeloma
(Abstract #8517)
This study of CyBorD was designed to determine response in patients with
newly diagnosed multiple myeloma. The results showed the status of 28
evaluable patients, who received cyclophosphamide at 300 mg/m2 on days 1, 8,
15, 22, VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11, and dexamethasone at 40
mg on days 1 through 4, 9 through 12, and 17 through 20 of a 28-day schedule.
A total of four cycles was planned with a goal of proceeding on to stem cell
transplant (SCT). Results were presented by Craig Reeder, M.D., Assistant
Professor of Medicine, Mayo Clinic College of Medicine, and showed a CR rate
of 46 percent prior to transplant, a CR rate of 72 percent post-transplant and
an overall response rate (partial response or better) of 95 percent. Side
effects included thrombocytopenia, neutropenia, hyperglycemia and peripheral
neuropathy.
VELCADE, Pegylated-Lyposomal-Doxorubicin and dexamethasone (PAD or VcDD)
as Induction Therapy Prior to Reduced Intensity ASCT Followed by Lenalidomide
and Prednisone (LP) as Consolidation and Lenalidomide Alone as Maintenance
(Abstract #8518)
This study of PAD (VcDD) was designed to evaluate the VELCADE combination
as induction therapy prior to SCT in patients with newly diagnosed multiple
myeloma. The results showed the status of 86 evaluable patients who received
VELCADE at 1.3 mg/m2 on days 1, 4, 8, 11, DOXIL at 30 mg/m2 on day 4 and
dexamethasone at 40 mg on days 1 through 4, 8 through 11, 15 through 18 for
one cycle and on days 1 through 4 for cycles two through four.
Cyclophosphamide at 3 g/m2 and G-CSF were used to harvest stem cells. Patients
were then conditioned with two courses of melphalan at 100 mg/m2 (MEL100).
Following SCT, patients received lenalidomide at 25 mg/day on days 1 through
21 plus prednisone at 50 mg every other day for four, 28-day LP cycles. This
was followed by lenalidomide alone at 10 mg/day on days 1 through 21 every 28
days. Results were presented by Antonio Palumbo, M.D., Chief of the Myeloma
Unit; Department of Hematology, University of Torino and showed 94 percent of
patients achieved at least a partial response, including a CR rate of 21
percent after four cycles of VcDD. Post transplant, the CR rate increased to
59 percent. After median follow up of 13.6 months, median progression-free
survival and overall survival have not been reached. Side effects were
manageable and included hematologic toxicity and peripheral neuropathy.
Safety and Efficacy of Lenalidomide, VELCADE and dexamethasone in Patients
with Newly Diagnosed Multiple Myeloma: A Phase I/II Study (Abstract #8520)
This Phase I/II study of VcRD combination therapy was designed to
determine the maximum tolerated dose (MTD) and efficacy in previously
untreated MM patients. The preliminary analysis included 66 evaluable
patients, who received VELCADE at 1.0 mg/m2 or 1.3 mg/m2 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 or 20 mg on the day of and day
after each VELCADE dose. Patients were treated for up to eight cycles at four
planned dose levels. Maximum planned dose was VELCADE 1.3 mg/m2, lenalidomide
25 mg and dexamethasone 20 mg. Response was assessed by modified EBMT criteria
and International Myeloma Working Group criteria. Results were presented by
Paul Richardson, M.D., Associate Professor of Medicine, Harvard Medical
School; Clinical Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber
Cancer Institute, Boston and showed a CR rate of 35 percent at maximum planned
dose and a 100 percent overall response rate (CR + partial response). Side
effects were manageable and included lymphopenia, thrombocytopenia,
hypophosphatemia and neutropenia. No grade 4 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 median age
of onset is 70 years), 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, The Takeda
Oncology Company, 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 100,000 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.
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, The Takeda Oncology Company, 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 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. Additional information about
Millennium is available through its website, 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. 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: www.millennium.com
(1) Complete remission includes both immunofixation positive and negative
readouts
Media Contacts:
Jennifer Snyder Karen Gobler
(617) 444-1439 (617) 444-1392
SOURCE Millennium Pharmaceuticals, Inc.
Jennifer Snyder, +1-617-444-1439, or Karen Gobler, +1-617-444-1392, both for
Millennium Pharmaceuticals, Inc.
