SAN FRANCISCO, Dec. 8 /PRNewswire/ -- Millennium: The Takeda Oncology
Company today reported updated results from two large, multi-center,
randomized Phase III clinical trials of VELCADE based combinations for the
induction treatment of transplant-eligible patients with previously untreated
multiple myeloma (MM). Prolonged progression-free survival (PFS) was observed
in one study comparing VELCADE and dexamethasone (VcD) with vincristine,
adriamycin and dexamethasone (VAD), as well as in another study comparing
VELCADE, thalidomide and dexamethasone (VcTD) with thalidomide and
dexamethasone (TD). These data were presented at the 50th Annual Meeting of
the American Society of Hematology (ASH), held December 5-9, 2008 in San
Francisco, California.
(Logo: http://www.newscom.com/cgi-bin/prnh/20080827/NEW076LOGO )
"VELCADE based combinations continue to deliver high response rates,
including complete responses," said Nancy Simonian, M.D., Chief Medical
Officer, Millennium. "It is impressive to see that this already translates to
improved progression-free survival when VELCADE regimens are used in
conjunction with high dose therapy and stem cell transplantation."
VELCADE-Dexamethasone versus VAD as Induction Treatment Prior to ASCT in
Newly Diagnosed Multiple Myeloma: Updated Results of the IFM2005/01 Trial
(ASH/ASCO Joint Symposium)
This 482-patient Phase III trial was conducted by the Intergroupe
Francophone du Myelome (IFM) cooperative group and Nantes University Hospital
(France). The updated results, which were presented by Professor Harousseau,
showed:
-- The two year PFS was 69 percent in the VcD arm, compared with 60
percent in the VAD arm (p=0.0115).
-- Post-induction complete response (CR)/near complete response (nCR)
rates were 15 percent in the VcD arm, compared with 7 percent in the
VAD arm (p=0.0035).
-- After the first performed ASCT, CR/nCR rates were 40 percent in the VcD
arm, compared with 22 percent in the VAD arm (p=0.0001).
-- After the first performed ASCT, very good partial response (VGPR) or
better rates were 61 percent in the VcD arm, compared with 44 percent
in the VAD arm (p=0.0007).
-- Thirty-four percent of patients in the VcD arm required a second ASCT,
compared with 47 percent of patients in the VAD arm.
-- Serious adverse events were reported in 27 percent of the VcD patients,
compared with 34 percent of the VAD patients.
"The data from patients treated with VELCADE and dexamethasone prior to
transplantation showed significantly longer progression-free survival," said
Jean-Luc Harousseau, M.D., Hospital Hotel-Dieu and Principal Investigator of
the trial. "We are interested in whether this will translate into extended
overall survival for these patients with previously untreated multiple myeloma
when the follow-up duration is sufficient."
Patients in the VcD arm received VELCADE at 1.3 mg/m(2) on days 1, 4, 8
and 11 and dexamethasone at 40 mg on days 1 through 4 during cycles 1 through
4 and days 9 through 12 during only the first and second cycles. Patients in
the VAD arm received vincristine at 0.4 mg/m(2) and doxorubicin at 9 mg/m(2)
on days 1 through 4, and dexamethasone at 40 mg on days 1 through 4 during
cycles 1 through 4 and on days 9 through 12 and 17 through 20 during only the
first and second cycles.
Superior Complete Response Rate and Progression-Free Survival After
Autologous Transplantation with Up-Front VELCADE-Thalidomide-Dexamethasone
Compared with Thalidomide-Dexamethasone in Newly Diagnosed Multiple Myeloma
(Abstract #158)
In a Phase III study conducted by the Italian Myeloma Network GIMEMA,
researchers compared VcTD with TD as induction therapy in preparation for and
as consolidation after melphalan-based double ASCT in 460 patients with
symptomatic MM. The median follow-up was 15 months.
The updated results, which were presented by Michele Cavo, M.D., Seragnoli
Institute of Hematology and Medical Oncology, showed:
-- The two-year PFS was 90 percent in the VcTD arm, compared with 80
percent in the TD arm (p=0.009).
-- After three cycles of induction, CR/nCR rates were 32 percent in the
VcTD arm, compared with 12 percent in the TD arm (p<0.001).
-- After the first ASCT, CR/nCR rates were 55 percent in the VcTD arm,
compared with 32 percent in the TD arm (p<0.001).
-- After the first ASCT, VGPR or better rates were 76 percent in the VcTD
arm, compared with 58 percent in the TD arm (p<0.001).
-- Serious adverse events were recorded in 15 percent of patients in the
VcTD arm, compared with 12 percent of those in the TD arm.
Patients in the VcTD arm received 1.3 mg/m(2) of VELCADE on days 1, 4, 8
and 11; 200 mg of thalidomide daily and 40 mg of dexamethasone on days 1, 2,
4, 5, 8, 9, 11 and 12. Patients in the TD arm received 200 mg of thalidomide
daily and 40 mg of dexamethasone on days 1 through 4 and 9 through 12 for
three 21-day cycles.
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 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. VELCADE is
approved in more than 87 countries worldwide.
Important Safety Information
In the U.S., VELCADE is indicated for the treatment of patients with
multiple myeloma. VELCADE also 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 throughout therapy, cardiac and pulmonary disorders,
reversible posterior leukoencephalopathy syndrome, gastrointestinal adverse
events, thrombocytopenia, neutropenia, tumor lysis syndrome and hepatic
events. Women of childbearing potential should avoid becoming pregnant while
being treated with VELCADE. Nursing mothers are advised not to breastfeed
while receiving 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 new onset of decreased left
ventricular ejection fraction has been reported, including reports in patients
with no risk factors for decreased left ventricular ejection fraction. There
have been 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. There have been 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. Cases of acute liver failure have been reported in patients
receiving multiple concomitant medications and with serious underlying medical
conditions. Patients who are concomitantly receiving VELCADE and drugs that
are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored
for either toxicities or reduced efficacy. Patients on oral antidiabetic
medication while receiving VELCADE should check blood sugar levels frequently.
Adverse Reaction Data
Safety data from Phase II and III studies of single-agent VELCADE 1.3
mg/m(2)/dose twice weekly for 2 weeks followed by a 10-day rest period in 1163
patients with previously treated multiple myeloma (N=1008, not including the
Phase III, VELCADE plus DOXIL(R) [doxorubicin HCl liposome injection] study)
and previously treated 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%), anemia (29%), edema (23%), headache,
paresthesia and dysesthesia and headache (each 22%), dyspnea (21%), cough and
insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness
(excluding vertigo) (each 17%), pain in limb and abdominal pain (each 15%),
bone pain (14%), back pain and hypotension (each 13%), herpes zoster,
nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia
(each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%).
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%).
In the Phase III VELCADE + melphalan and prednisone study, the safety
profile of VELCADE in combination with melphalan/prednisone is consistent with
the known safety profiles of both VELCADE and melphalan/prednisone. The most
commonly reported adverse events for VELCADE in combination with MP vs MP,
respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%),
nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%),
anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%),
leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue
(29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21%
vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs
10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%),
dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in
extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%),
herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%),
hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12%
vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs
10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).
About Millennium
Millennium: 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 Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company
Ltd. ("Takeda", TSE: 4502) in May, 2008. The Company's research, development
and commercialization activities are focused in oncology. Additional
information about Millennium is available through its website,
http://www.millennium.com.
Editors' Note: This press release is also available under the Media
section of the Company's website at: http://www.millennium.com.
Contact:
Manisha Pai Karen Gobler
(617) 551-7877 (617) 444-1392
Manisha.Pai@mpi.com Karen.Gobler@mpi.com
