KOS, Greece, June 28 2007 /PRNewswire-FirstCall/ -- Millennium Pharmaceuticals, Inc. today reported on data presentations of VELCADE that showed improved outcomes for multiple myeloma (MM) patients affected by bone degeneration and renal impairment. MM is a plasma cell disease and carries significant risk of bone erosion and skeletal compromise. In addition, kidney function frequently is impaired. Approximately 50 percent of patients will experience renal dysfunction in the course of their disease. The clinical findings were presented at the prestigious 11th International Myeloma Workshop (IMW) in Kos, Greece. Highlights included:
(Logo: http://www.newscom.com/cgi-bin/prnh/19991220/MLNMLOGO ) -- In patients affected by MM-related bone degeneration, VELCADE and dexamethasone combination therapy demonstrated an increase in biomarkers indicative of bone formation. These results validate findings from a previously presented study, which measured actual patient biopsies for improvement in bone volume and thickness and found that VELCADE promoted bone growth. -- In a retrospective analysis of a clinical trial, VELCADE showed comparable positive median overall survival (OS) and overall response rate (ORR) in patients both with renal impairment and those with normal renal function. In a supporting study of MM patients with increased biomarker levels indicating poor renal function and poor survival prognosis, VELCADE produced a high ORR and improved renal function.
"VELCADE not only demonstrates a survival benefit for previously treated multiple myeloma patients, but also it can be used in patients with common disease-related complications, such as bone degeneration and renal impairment. VELCADE is the only agent that has shown this consistently and does not require dose modifications," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "These data further underscore the need to use VELCADE broadly, offering comprehensive care for patients."
VELCADE Plus Dexamethasone Therapy Induces Osteoblast Activation in Responsive Patients with Multiple Myeloma (Abstract #PO-311)
The Phase II trial assessed bone metabolism and efficacy of VELCADE and dexamethasone combination therapy in patients with relapsed / refractory MM. The study enrolled 14 patients who received VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Patients also received 20 mg of dexamethasone on days 1, 2, 4, 5, 8, 9, 11 and 12. Results were presented by Shuji Ozaki, M.D., The University of Tokushima Graduate School of Health Biosciences, and showed an ORR (very good partial response + partial response) of 71 percent. A rapid increase of serum alkaline phosphatase (ALP) was observed in treatment-responsive patients. Bone formation markers such as serum bone specific ALP and osteocalcin significantly increased in six and three patients, respectively. Additionally, a radiographic examination showed fewer bone lesions. These findings suggest that VELCADE based therapy induced osteoblast activation. Side effects were manageable, including thrombocytopenia, peripheral neuropathy and ileus.
These results support a previous study presented by Maurizio Zangari, M.D., University of Arkansas for Medical Sciences, at the 2007 European Hematology Association meeting. In the study of 10 evaluable relapsed / refractory MM patients, VELCADE was administered at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Patients were treated for three cycles. Bone biopsies were obtained at baseline and, after treatment, measured bone volume / total volume in trabecular thickness by micro-computed tomography. Bone formation also was determined by histomorphometry. Results showed an increase in bone volume equal to or greater than 40 percent from baseline in four out of five patients after just 12 weeks of therapy. A parallel increase in trabecular thickness also was observed, showing a positive skeletal response to the therapy.
VELCADE in Renally Impaired Multiple Myeloma Patients (Abstract #PO-1114)
The retrospective analysis of the APEX Phase III study assessed VELCADE efficacy and safety in patients with varying degrees of renal impairment. The APEX trial had compared VELCADE to high-dose dexamethasone in MM patients, who had received one to three prior therapies, and showed 29.8 months median OS for patients on VELCADE, a six-month benefit over high-dose dexamethasone. The retrospective analysis included data from 313 evaluable patients. Response rate, time to progression (TTP) and OS were analyzed in four sub- groups of patients, ranging from severe to no renal impairment as classified by creatinine clearance levels. Results were presented by Jesus San Miguel, M.D., Ph.D., Hospital Universitario de Salamanca, and showed that response rate, TTP and OS for patients on VELCADE were similarly positive across all four patient sub-groups. Time to response was rapid, which is the goal of treatment for patients with renal impairment. Given the survival benefit seen in these patients, VELCADE may overcome poor prognosis associated with renal impairment. Adverse events, discontinuations and dose reductions also were similar across all four patient sub-groups.
Cystatin-C: an Early Marker of Renal Impairment and an Independent Predictive Factor for Survival in Multiple Myeloma. Reduction Post-VELCADE Therapy (Abstract #PO-227)
The Phase II study was designed not only to evaluate the impact of VELCADE on serum levels of Cystatin-C, an early biomarker for poor renal function, but also to explore possible correlations with clinical response, including survival. Impaired renal function is known to be an indicator of poor survival prognosis. The study included 155 MM patients who were treated with VELCADE at 1.3 mg/m2 on days 1, 4, 8 and 11 of a 21-day schedule. Results were presented by Evangelos Terpos, M.D., General Airforce Hospital, and showed that VELCADE reduced Cystatin-C levels, demonstrating effectiveness in patients with decreased renal function, and the potential ability to improve survival in these patients.
About Multiple Myeloma
Multiple myeloma 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 increasing incidence and younger age of onset. In the U.S., more than 50,000 individuals have multiple myeloma and 20,000 new cases are diagnosed each year. Worldwide there are approximately 74,000 new cases and over 45,000 deaths annually.
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 is approved in more than 80 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 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 multiple myeloma and mantle cell lymphoma studies, the most commonly reported adverse events were asthenic conditions (64%), nausea (55%) in single-agent VELCADE, diarrhea (52%), constipation (41%), peripheral neuropathy (39%), thrombocytopenia (36%), appetite decrease, 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. The most commonly reported serious adverse events 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. 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 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. 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
Editors' Note: This press release is also available under the Media section of the Company's website at: http://www.millennium.com.
Contacts:
Jennifer Snyder (media) Kyle Kuvalanka (investors) (617) 448-0281 (857) 498-0818
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