Publication of Clinical Results Underscores Velcade (Bortezomib) For Injection Based Therapy As a Standard of Care In Newly Diagnosed Multiple Myeloma Patients
CAMBRIDGE, Mass., March 13, 2008 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. today announced the publication of updated results of the Phase I/II clinical trial of the combination therapy VELCADE, melphalan and prednisone (VcMP) in newly diagnosed multiple myeloma patients, who were ineligible for stem cell transplantation. Results of this study included one of the highest reported complete remission (CR) rates, which is an important indicator for long-term survival, and the highest three- year survival rate reported in the non-transplant setting. These results provided the basis for the Phase III VISTA trial. The Company submitted a supplemental New Drug Application (sNDA) to the U.S. Food and Drug Administration (FDA) in December 2007 for VELCADE expansion into newly diagnosed multiple myeloma. The FDA decision date for the sNDA is scheduled for June 20, 2008. The Company's co-development partner, Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD) also has filed a corresponding application with the European Medicines Evaluation Agency.
"These results support the strong relationship between high rates of durable complete remissions with long-term survival in patients with newly diagnosed multiple myeloma," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "We are confident that VELCADE will be a key component of the standard of care in this patient setting."
The study was pre-published online in the journal, Haematologica. Data from the 60 patient Phase I/II trial conducted by the PETHEMA Foundation in Spain were evaluated by the stringent European Group for Blood and Marrow Transplantation (EBMT) criteria and results are as follows:
-- Results showed an immunofixation-negative CR rate of 32 percent and an overall response rate (ORR) of 89 percent with VcMP. -- The overall survival rate at 38 months was 85 percent with VcMP compared to the 38 percent historical control with melphalan and prednisone (MP) (p<0.0001). The median overall survival for VcMP has not been reached compared to 26 months among the historical control with MP. -- The median time-to-disease progression (TTP) with VcMP of 27.2 months compared to 20 months for the historical control with MP (p=0.001). -- The median event-free survival (EFS) with VcMP of 25 months compared to 15 months for the historical control with MP (p=0.001). -- VcMP was well tolerated in this elderly patient population (median age of 75) with patients on therapy for more than nine months. The safety profile was predictable and manageable.
Patients received VELCADE at 1.3 mg/m2 (n=54) or 1.0 mg/m2 (n=6) twice weekly in weeks one, two, four and five for four six-week cycles (eight doses per cycle), followed by once weekly in weeks one, two, three and four for five, five-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. Treatment continued for a maximum of 49 weeks (52 vials) with a median number of 39 weeks (42 vials) reported in the trial. The safety profile of VcMP was as expected based on the known safety profile of each of the individual agents in the combination, including thrombocytopenia, neutropenia and peripheral neuropathy.
About Multiple Myeloma
Multiple myeloma is the second most common hematological 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 multiple myeloma and approximately 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. 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 85,000 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. This integrated analysis does not include the Phase III, 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(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. 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.
Editors' Note: This press release is also available under the Media section of the Company's website at: www.millennium.com
Jennifer Snyder (media) Kyle Kuvalanka (investors)
(617) 444-1439 (617) 761-4734
CONTACT: Media: Jennifer Snyder, +1-617-444-1439; Investors: KyleKuvalanka, +1-617-761-4734, both for Millennium Pharmaceuticals, Inc.
Web site: http://www.millennium.com/
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Ticker Symbol: (NASDAQ-NMS:MLNM)
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Posted: March 2008