CHICAGO, May 31 /PRNewswire/ -- Millennium Pharmaceuticals, The Takeda
Oncology Company, today announced the presentation of results from three
clinical trials of VELCADE based therapies that showed consistently high
complete remission(1) (CR) rates in patients with newly diagnosed multiple
myeloma (MM). CR is one of the best predictors of long-term survival. These
three studies were selected for oral presentation at the American Society
of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois, May 30 -
June 3, 2008. Highlights included:
-- VELCADE, cyclophosphamide, and dexamethasone (CyBorD) demonstrated a
CR rate of 46 percent prior to transplant and 72 percent
-- VELCADE, DOXIL and dexamethasone (PAD or VcDD) prior to transplant
showed a CR rate of 21 percent which increased to 59 percent
-- VELCADE, lenalidomide and dexamethasone (VRD) showed a CR rate of 35
percent at maximum planned dose and a 100 percent overall response
"The goal of first-line therapy is to rapidly achieve the deepest and most durable response possible," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "VELCADE based combinations produce among the highest CR rates that are similar to those achieved by high dose therapy and transplantation. These very strong results underscore the critical role of VELCADE in patients with newly diagnosed multiple myeloma."
Efficacy of Induction with CyBorD in Newly Diagnosed Multiple Myeloma (Abstract #8517)
This study of CyBorD was designed to determine response in patients with newly diagnosed multiple myeloma. The results showed the status of 28 evaluable patients, who received cyclophosphamide at 300 mg/m2 on days 1, 8, 15, 22, VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11, and dexamethasone at 40 mg on days 1 through 4, 9 through 12, and 17 through 20 of a 28-day schedule. A total of four cycles was planned with a goal of proceeding on to stem cell transplant (SCT). Results were presented by Craig Reeder, M.D., Assistant Professor of Medicine, Mayo Clinic College of Medicine, and showed a CR rate of 46 percent prior to transplant, a CR rate of 72 percent post-transplant and an overall response rate (partial response or better) of 95 percent. Side effects included thrombocytopenia, neutropenia, hyperglycemia and peripheral neuropathy.
VELCADE, Pegylated-Lyposomal-Doxorubicin and dexamethasone (PAD or VcDD) as Induction Therapy Prior to Reduced Intensity ASCT Followed by Lenalidomide and Prednisone (LP) as Consolidation and Lenalidomide Alone as Maintenance (Abstract #8518)
This study of PAD (VcDD) was designed to evaluate the VELCADE combination as induction therapy prior to SCT in patients with newly diagnosed multiple myeloma. The results showed the status of 86 evaluable patients who received VELCADE at 1.3 mg/m2 on days 1, 4, 8, 11, DOXIL at 30 mg/m2 on day 4 and dexamethasone at 40 mg on days 1 through 4, 8 through 11, 15 through 18 for one cycle and on days 1 through 4 for cycles two through four. Cyclophosphamide at 3 g/m2 and G-CSF were used to harvest stem cells. Patients were then conditioned with two courses of melphalan at 100 mg/m2 (MEL100). Following SCT, patients received lenalidomide at 25 mg/day on days 1 through 21 plus prednisone at 50 mg every other day for four, 28-day LP cycles. This was followed by lenalidomide alone at 10 mg/day on days 1 through 21 every 28 days. Results were presented by Antonio Palumbo, M.D., Chief of the Myeloma Unit; Department of Hematology, University of Torino and showed 94 percent of patients achieved at least a partial response, including a CR rate of 21 percent after four cycles of VcDD. Post transplant, the CR rate increased to 59 percent. After median follow up of 13.6 months, median progression-free survival and overall survival have not been reached. Side effects were manageable and included hematologic toxicity and peripheral neuropathy.
Safety and Efficacy of Lenalidomide, VELCADE and dexamethasone in Patients with Newly Diagnosed Multiple Myeloma: A Phase I/II Study (Abstract #8520)
This Phase I/II study of VcRD combination therapy was designed to determine the maximum tolerated dose (MTD) and efficacy in previously untreated MM patients. The preliminary analysis included 66 evaluable patients, who received VELCADE at 1.0 mg/m2 or 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Patients also received lenalidomide at 15, 20 or 25 mg on days 1 through 14 and dexamethasone at 40 or 20 mg on the day of and day after each VELCADE dose. Patients were treated for up to eight cycles at four planned dose levels. Maximum planned dose was VELCADE 1.3 mg/m2, lenalidomide 25 mg and dexamethasone 20 mg. Response was assessed by modified EBMT criteria and International Myeloma Working Group criteria. Results were presented by Paul Richardson, M.D., Associate Professor of Medicine, Harvard Medical School; Clinical Director, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston and showed a CR rate of 35 percent at maximum planned dose and a 100 percent overall response rate (CR + partial response). Side effects were manageable and included lymphopenia, thrombocytopenia, hypophosphatemia and neutropenia. No grade 4 peripheral neuropathy was observed.
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), recent statistics indicate both increasing incidence and younger age of onset. In the U.S., more than 50,000 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, 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 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 100,000 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.
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, The Takeda Oncology Company, 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 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. Additional information about Millennium is available through its website, http://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. 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: http://www.millennium.com
(1) Complete remission includes both immunofixation positive and negative
Jennifer Snyder Karen Gobler
(617) 444-1439 (617) 444-1392
|SOURCE Millennium Pharmaceuticals, Inc.|
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