CAMBRIDGE, Mass., Aug. 27 — Millennium: The Takeda
Oncology Company today announced the publication of results from the 682
patient, randomized, Phase III VISTA(1) trial in this week’s edition of the
New England Journal of Medicine. The results showed a significant survival
benefit and a 30 percent complete remission (CR) rate with VELCADE,
melphalan and prednisone (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.
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“These data demonstrate that treatment with VELCADE plus melphalan and
prednisone leads to a survival benefit and a high complete 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 trial. “The combination of
VELCADE plus melphalan and prednisone is an important new option for these
patients.”
These data originally were presented at the 2007 American Society of
Hematology (ASH) Annual Meeting. Based on these positive trial 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 data published in such a highly esteemed
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 melphalan 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<0.001)
– VcMP demonstrated statistical significance in overall survival with
a 39 percent reduction in risk of death (Hazard ratio= 0.61; p=0.008) with
a follow-up of 16.3 months
– The median treatment duration was 46 weeks for the VcMP arm compared
to 39 weeks for the control arm and discontinuation due to adverse 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 five for four six-week cycles (eight doses per
cycle), followed by once weekly on weeks one, two, four and five for up to
five six-week cycles (four doses per cycle) in combination with melphalan
at 9 mg/m2 and prednisone at 60 mg/m2 once 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
generally 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
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%).
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/m2/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 greater than or equal to 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%).
About Multiple Myeloma
Multiple myeloma is the second most common hematological malignancy.
Between 2001 – 2005, the median age of diagnosis was 70 years. 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 increase 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 rest
of the world. Janssen Pharmaceutical K.K. is responsible for
commercialization in Japan. 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: 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 commercialization
activities are focused in oncology. Additional information about Millennium
is available through its website, http://www.millennium.com.
Media Contact:
Karen Gobler
(617) 444-1392
karen.gobler@mpi.com
SOURCE Millennium