ORLANDO, Fla., Dec. 12 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. today reported the presentation of results of several clinical trials of VELCADE(R) (bortezomib) for Injection in combination with a variety of agents, including DOXIL(R) (pegylated liposomol doxorubicin) and dexamethasone, for the treatment of newly diagnosed multiple myeloma (MM) patients. Studies showed VELCADE combination therapy produced very good partial response and complete response (VGPR/CR) rates as high as 53 percent as induction therapy, which improved to 79 percent following autologous stem cell transplantation (ASCT). In a study of VELCADE in combination with dexamethasone, the one-year survival rate was 92 percent after a median follow up of 24 months. These findings were reported at the 48th Annual Meeting and Exposition of the American Society of Hematology (ASH), December 9-12, 2006, in Orlando, Fla.
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"Evidence continues to build that VELCADE based regimens provide high VGPR/CR rates in front-line patients as induction therapy prior to stem cell transplantation," said Nancy Simonian, M.D., Senior Vice President and Chief Medical Officer, Millennium. "With these high CR rates, we believe we are starting to see the benefit of VELCADE on improved post-transplant outcomes."
Long-Term Follow Up of Patients Treated with VELCADE (Bortezomib) Alone and in Combination with Dexamethasone as Front-line Therapy for Multiple Myeloma (Abstract #796)
The long-term follow up of a Phase II clinical trial evaluated VELCADE in combination with dexamethasone in 48 evaluable newly diagnosed MM patients. Patients with measurable disease received VELCADE at 1.3 mg/m2 on days 1, 4, 8, and 11 of a three-week cycle for up to six cycles. Oral dexamethasone at 40 mg was added to the treatment regimen on the day of and day after VELCADE for patients not achieving partial response (PR) after two cycles or for patients not achieving a CR after four cycles. Responses were assessed using modified European Group for Blood and Marrow Transplantation (EBMT) criteria. The study was presented by Sundar Jagannath, M.D., of St. Vincent's Comprehensive Cancer Center, New York, N.Y. on behalf of the Aptium Oncology Research Network, Los Angeles, Calif. Results showed:
-- Overall response rate (ORR) was 88 percent including an 18 percent CR/near complete response (nCR) rate and a 20 percent VGPR rate -- For all patients, with a median follow up of 27 months, median overall survival had not yet been reached; one- and two-year survival rates were 92 and 85 percent, respectively -- For patients not proceeding to ASCT, with a median follow up of 27 months, two-year survival rate was 81 percent -- Collection of stem cells was not impaired for patients proceeding to ASCT -- Therapy was well tolerated; the most frequent adverse events were sensory neuropathy/neuropathic pain, fatigue and constipation
High Rate of Complete and near Complete Responses after Initial Therapy with VELCADE (Bortezomib), DOXIL, and Dexamethasone (VDD) Is Further Increased after Autologous Stem Cell Transplantation (Abstract #3093)
The Phase II clinical trial evaluated VELCADE in combination with DOXIL plus dexamethasone (VDD) in 28 evaluable newly diagnosed MM patients. The primary goals of the study were to measure CR/nCR of VDD pre- and post- transplantation and to explore whether an improved quality of response prior to ASCT would improve the overall chances of survival post-transplantation. Responses were assessed using modified EBMT criteria. Six three-week cycles of VELCADE at 1.3 mg/m2 were administered on days 1, 4, 8, and 11. DOXIL at 30 mg/m2 was administered on day four and dexamethasone at 40 mg on days one to four for the first 10 patients and at 20 mg on days 1, 2, 4, 5, 8, 9, 11 and 12 for the remaining patients (for a total dose of 160 mg of dexamethasone per cycle). The data were presented by Andrzej Jakubowiak, M.D., Ph.D., of the University of Michigan Comprehensive Cancer Center in Ann Arbor, Mich. Results showed:
-- VDD achieved a strong ORR as induction therapy - ORR was 89 percent, with a CR/nCR of 32 percent and with 53 percent achieving a CR/VGPR -- VDD appeared to improve probability of achieving CR/nCR and VGPR after transplantation compared to results from randomized studies with single or tandem transplantation - In the 17 patients who went on to ASCT, ORR improved to 96 percent with 54 percent achieving CR/nCR and 79 percent achieving a CR/VGPR - Collection of stem cells was not impaired by this regimen -- The most common adverse events were fatigue, pneumonia/infection and neuropathy (only mild)
VELCADE (Bortezomib) and Pegylated Liposomal Doxorubicin as Induction Therapy for Adult Patients with Symptomatic Multiple Myeloma: Cancer and Leukemia Group B Study 10301 (Abstract #797)
The multicenter Phase II study assessed the safety and efficacy of the steroid-free combination of VELCADE and DOXIL in 57 evaluable newly diagnosed MM patients as induction therapy prior to ASCT. Responses were assessed using modified EBMT. VELCADE was administered at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day cycle, along with DOXIL at 30 mg/m2 on day four, for a maximum of eight cycles. Data from 29 evaluable patients were presented by Robert Orlowski, M.D., Ph.D., of the University of North Carolina at Chapel Hill for the Cancer and Leukemia Group B cooperative group. Results showed:
-- After induction therapy prior to stem cell transplantation, ORR was 79 percent with a 28 percent CR/nCR rate -- Treatment did not affect stem cell collection in patients evaluable for this endpoint -- Therapy was well tolerated; the most common adverse events were neutropenia, thrombocytopenia (hematologic), fatigue and sensory neuropathy (non-hematologic)
VELCADE is the U.S. market leader for relapsed MM. Previous studies in relapsed MM have demonstrated single-agent VELCADE has unprecedented survival. In newly diagnosed patients, VELCADE based therapies have achieved transplant- like results with ORRs of up to 95 percent and CR/nCR rates of up to 43 percent. The studies presented today along with the interim data from the Phase III trial presented by the Intergroupe Francophone du Myelome on Sunday continue to show some of the highest recorded CR/nCR rates for a therapeutic agent in the treatment of front-line MM.
About Multiple Myeloma
MM is the second most common hematologic malignancy and although the disease is predominantly a cancer of the elderly (the average age of onset is 65 to 70 years of age), recent statistics indicate both an increasing incidence and a younger age of onset. In the U.S., more than 50,000 individuals have MM and over 15,000 new cases are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths annually.(1)
About VELCADE
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. will co-promote VELCADE in the U.S. VELCADE also is approved in the European Union after first relapse.
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 (MCL) 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 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 (ARDS) 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 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.
Safety Data: In 1163 patients in MM and MCL studies, the most commonly reported adverse events were asthenic conditions (64%), nausea (55%), diarrhea (52%), constipation (41%), peripheral neuropathy (39%), thrombocytopenia (36%), appetite decreased, including reports of anorexia (36%), pyrexia (34%), vomiting (33%) and anemia (29%). Twenty percent of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (5%) and neutropenia (3%). Fifty percent of patients reported serious adverse events (SAEs). The most commonly reported SAEs were pneumonia (7%), pyrexia (6%), diarrhea (5%), vomiting (4%), and nausea, dehydration, dyspnea and thrombocytopenia (each 3%).
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 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. The Company'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. The Company'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.
1. American Cancer Society, Overview: Multiple Myeloma, 2005, http://www.cancer.org Contacts: Jennifer Snyder (media) Kyle Kuvalanka (investors) (617) 448-0281 (857) 498-0818
Photo: NewsCom: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGOAP Archive: http://photoarchive.ap.orgPRN Photo Desk, photodesk@prnewswire.comMillennium Pharmaceuticals, Inc.CONTACT: Media, Jennifer Snyder, +1-617-448-0281, or Investors, KyleKuvalanka, +1-857-498-0818, both for Millennium Pharmaceuticals, Inc.
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