Healthcare Industry News: Ortho Biotech
News Release - December 9, 2007
Highest Reported Complete Remission Rate of 35 Percent Achieved in a Phase III Front-Line Multiple Myeloma Trial With Velcade(R) (Bortezomib) for Injection Based TherapyVELCADE based therapy achieved highly significant improvement across all efficacy endpoints including overall survival
ATLANTA, Dec. 9 (HSMN NewsFeed) -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM ) today announced the presentation of results from the 682 patient, randomized, Phase III VISTA(1) trial. These patients with previously untreated multiple myeloma (MM) were ineligible for stem cell transplantation (SCT). The trial compared VELCADE, melphalan and prednisone (VcMP) to melphalan and prednisone (MP) alone, a recognized standard of care in this treatment setting. These data were selected for an oral presentation at the American Society of Hematology (ASH) 49th Annual Meeting in Atlanta, Ga., December 8-11, 2007.
"The goal of therapy is long-term survival and complete remission is a well-known indicator for survival," said Professor Jesus San-Miguel, M.D., Hematology Department Head, University Hospital of Salamanca and Principal Investigator of the trial. "Data from this rigorously-controlled trial clearly show that VELCADE based therapy should be a standard of care for previously untreated patients, who are not able to receive stem cell transplantation."
Data from the large international clinical trial were presented by Professor San-Miguel. Responses were evaluated by the commonly used M-protein levels measured in serum or urine by a centralized laboratory as well as the most stringent European Group for Blood and Marrow Transplantation (EBMT) criteria:
-- Immunofixation-negative complete remission (CR) rate of 35 percent in the VcMP arm compared to 5 percent with MP (p<0.000001); EBMT criteria showed a CR rate of 30 percent in the VcMP arm compared to 4 percent with MP
-- The median duration of response was 24 months for patients with CR in VcMP compared to 13 months with MP
-- Time-to-disease progression (TTP) in the VcMP arm of 24 months compared to 17 months with MP (p=0.0000001)
-- VcMP demonstrated statistical significance in overall survival with a 40 percent reduction in risk of death (p=0.0078); median survival was not reached despite a short follow-up of 16 months
-- The median treatment duration was 46 weeks and discontinuation due to adverse events was low and similar in both arms
"This VELCADE based therapy offers patients durable and complete remissions, formerly only accessible to transplant patients," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "We are filing a sNDA this month to seek approval in this important treatment setting, which could significantly increase the number of patients eligible to benefit from VELCADE."
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 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. Patients in the MP arm received nine six-week cycles of MP once daily on days 1 through 4. For both groups, treatment continued for a maximum of 54 weeks (52 vials) with a median number of 46 weeks (44 vials) reported in the trial. The safety profile of VcMP was as expected based on the known safety profile of each of the three individual agents in the combination, including neutropenia, thrombocytopenia, anemia and peripheral neuropathy.
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 of age), recent statistics indicate both increasing incidence and younger age of onset. In the U.S., more than 55,000 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.
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. are co-promoting VELCADE in the U.S. VELCADE is approved in more than 85 countries worldwide.
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 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 2 and 3 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. This integrated analysis does not include the phase 3, VELCADE plus DOXIL study.
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).
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. Millennium'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. Millennium's website is 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® (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.
(1) VELCADE as Initial Standard Therapy in multiple myeloma: Assessment with melphalan and prednisone
Source: Millennium Pharmaceuticals
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