�Millennium: The Takeda
Oncology Company proclaimed the publication of results from the 682
patient role, randomized, Phase III VISTA(1) trial in this week's edition of the
New England Journal of Medicine. The results showed a significant natural selection
benefit and a 30 percent nail remission (CR) rate with VELCADE,
alkeran and meticorten (VcMP) compared to 4 percent for melaphalan and
prednisone (MP) alone in previously untreated multiple myeloma patients.
Multiple myeloma is the second most common blood cancer.
"These data demonstrate that treatment with VELCADE asset melphalan and
prednisone leads to a survival benefit and a high nail remission in
previously untreated patients with multiple myeloma," said Professor Jesus
San Miguel, M.D., Ph.D., Hematology Department Head, University Hospital of
Salamanca and Principal Investigator of the test. "The combination of
VELCADE plus alkeran and meticorten is an important fresh option for these
patients."
These data originally were presented at the 2007 American Society of
Hematology (ASH) Annual Meeting. Based on these positive tribulation results, the
U.S. Food and Drug Administration approved VELCADE for patients with
previously untreated multiple myeloma on June 20, 2008. The Phase III VISTA
trial was conducted by Millennium and its co-development partner Johnson &
Johnson Pharmaceutical Research & Development, L.L.C. in 151 centers
worldwide.
"We are proud to have these information published in such a highly honored
journal," said Nancy Simonian, M.D., Chief Medical Officer, Millennium.
"We're delighted that previously untreated multiple myeloma patients now
can benefit from this VELCADE based therapy as have patients in the
relapsed and refractory settings since 2003."
(1) VELCADE as Initial Standard Therapy in multiple myeloma: Assessment
with alkeran and prednisone
VISTA Trial Results
Patient responses were evaluated by the stringent European Group for
Blood and Marrow Transplantation (EBMT) criteria:
-- A CR rate of 30 percent in the VcMP arm compared to 4 percent with
MP (p
-- VcMP demonstrated statistical significance in overall survival with
a 39 percent reduction in danger of death (Hazard ratio= 0.61; p=0.008) with
a follow-up of 16.3 months
-- The median treatment continuance was 46 weeks for the VcMP arm compared
to 39 weeks for the control arm and discontinuation ascribable to inauspicious events
was similar in both arms
Patients in the VcMP arm received VELCADE at 1.3 mg/m2 twice weekly in
weeks one, two, four and basketball team for foursome six-week cycles (eight doses per
bike), followed by once weekly on weeks one, 2, four and five for up to
five six-week cycles (four doses per cycle) in combination with melphalan
at 9 mg/m2 and liquid Pred at 60 mg/m2 at one time daily on days 1 through 4 of
each cycle for up to nine six-week cycles. For both groups, treatment
continued for a maximum of 54 weeks.
"The tolerability of VcMP also was encouraging and side effects were
more often than not manageable with appropriate supportive care and dose reduction as
needed," commented Paul Richardson, M.D., Clinical Director of the Jerome
Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute and Senior
Investigator on the study.
The safety profile of VELCADE in combination with MP is consistent with
the known safety profiles of both VELCADE and MP. In VISTA, the most
usually reported untoward events for VELCADE in combination with MP vs MP,
respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%),
sickness (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%), skin rash (19% vs 7%), endorse 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 painfulness (14%
vs 7%), paraesthesia (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 in the neck (11% vs 10%), arthralgia (11% vs
15%) and pruritus (10% vs 5%).
Important Safety Information
In the U.S., VELCADE is indicated for the treatment of patients with
multiple myeloma. VELCADE besides is indicated for the treatment of patients
with mantle cell lymphoma world Health Organization 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 supervising 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 buns leukoencephalopathy syndrome,
gastrointestinal adverse events, thrombopenia, neutropenia, tumour lysis
syndrome and liverwort events. Women of childbirth potential should avoid
becoming pregnant spell being toughened 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 event
of peripheral neuropathy has not been studied in mantle cell lymphoma.
Acute development or exacerbation of congestive warmheartedness failure, and new
onset of decreased left ventricular ejection fraction has been reported,
including reports in patients with no risk factors for decreased leftfield
ventricular expulsion fraction. There have been reports of acute permeate
infiltrative pulmonary disease of unknown aetiology 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 buoy present with seizure, high blood pressure,
headache, inanition, confusion, cecity, and other visual and neurological
disturbances. VELCADE is associated with thrombocytopenia and neutropenia.
There have been reports of gastrointestinal and intracerebral bleeding in
association with VELCADE. Transfusions may be considered. Complete pedigree
counts (CBC) should be frequently monitored during discourse with VELCADE.
Cases of acute liver failure have been reported in patients receiving
multiple concomitant medications and with serious underlying medical
weather. Patients world Health Organization are concomitantly receiving VELCADE and drugs that
ar inhibitors or inducers of cytochrome P450 3A4 should be closely
monitored for either toxicities or decreased 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/m2/dose twice weekly for 2 weeks followed by a 10-day rest period in
1163 patients with previously treated multiple myeloma (N=1008, non
including the Phase III, VELCADE asset DOXIL(R) [doxorubicin HCl liposome
injection] study) and antecedently treated pallium cell lymphoma (N=155) were
integrated and tabulated. In these studies, the condom profile of VELCADE
was similar in patients with multiple myeloma and blanket cell lymphoma.
In the integrated depth psychology, the most commonly reported adverse events
were asthenic conditions (including fatigue, unease and weakness) (64%),
sickness (55%), looseness (52%), irregularity (41%), peripheral neuropathy NEC
(including peripheral sensory neuropathy and peripheral neuropathy
aggravated) (39%), thrombocytopenia and appetite decreased (including
anorexia) (each 36%), fever (34%), vomiting (33%), anemia (29%), hydrops
(23%), head ache, paresthesia and dysesthesia and headache (each 22%),
dyspnea (21%), coughing and insomnia (each 20%), rash (18%), arthralgia (17%),
neutropenia and dizziness (excluding vertigo) (each 17%), hurting in limb and
abdominal muscle pain (each 15%), os pain (14%), back pain in the neck and hypotension (each
13%), herpes zoster, nasopharyngitis, pep pill 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 greater than or equalize to Grade 4 toxicity, most unremarkably
thrombocytopenia (5%) and neutropenia (3%). A total of 50% of patients
experient serious untoward events (SAEs) during the studies. The most
ordinarily reported SAEs included pneumonia (7%), febrility (6%), looseness of the bowels
(5%), puking (4%), and nausea, dehydration, dyspnea and thrombocytopenia
(each 3%).
About Multiple Myeloma
Multiple myeloma is the endorsement most mutual hematological malignance.
Between 2001 - 2005, the medial age of diagnosis was 70 long time. In 2007,
there were 110,000 patients living with multiple myeloma across the United
States, Europe and Japan. It is estimated that this number will growth by
5.6 % annually over the next few years due to new therapies extending the
lives of multiple myeloma patients.
About VELCADE
VELCADE is being co-developed by Millennium: 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 perch
of the world. Janssen Pharmaceutical K.K. is responsible for
commercialisation in Japan.
About Millennium
Millennium: The Takeda Oncology Company, and 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 commercialisation
activities ar focused in oncology. Additional information about Millennium
is available through its site, http://www.millennium.com.
Millennium
http://www.millennium.com
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