Healthcare Industry News: Mantle Cell Lymphoma
News Release - June 28, 2007
VELCADE(R) (Bortezomib) for Injection Based Therapies Achieved Survival Rates as High as 100 Percent in Newly Diagnosed Multiple Myeloma Patients100 percent response rate achieved with VELCADE, lenalidomide and dexamethasone
KOS, Greece, June 28 (HSMN NewsFeed) -- Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM ) today reported on the presentation of results from four clinical trials of VELCADE based therapies that showed consistently high survival and complete remission / complete response(1) (CR) rates in newly diagnosed multiple myeloma (MM) patients. These data were presented at the prestigious 11th International Myeloma Workshop (IMW) in Kos, Greece. Highlights included:
-- VELCADE, melphalan and prednisone (VMP) demonstrated a CR(1) rate of 43 percent, the strongest rate ever reported for a melphalan prednisone combination therapy. At 38 months, 85 percent of patients were alive. This is the highest reported three-year survival rate in the front-line treatment setting.
-- VELCADE, adriamycin and dexamethasone (referred to as VcAD or PAD) showed a CR(1) rate of 29 percent prior to stem cell transplantation (SCT), which further improved to 57 percent following SCT. At one year, 100 percent of patients were alive, and at two years, 95 percent of patients were alive. This is the highest reported two-year survival rate in the front-line treatment setting. Median overall survival (OS) has not yet been reached after four years.
-- VELCADE, DOXIL® (pegylated liposomal doxorubicin) and dexamethasone (VDD) showed a CR(1) rate of 43 percent prior to SCT, which increased to 65 percent following SCT. At 16 months, 100 percent of patients were alive.
-- VELCADE, lenalidomide and dexamethasone (VRD) showed an overall response rate (ORR) of 100 percent, including a CR(1) rate of 20 percent.
"These spectacular results underscore the crucial role of VELCADE in front-line multiple myeloma," said Sagar Lonial, M.D., Emory University. "VELCADE has consistently delivered survival rates that are among the highest seen to date in this disease setting. These high survival rates were driven by the substantial complete remission rates seen when VELCADE has been added to multiple therapies. Oncologists generally use the most efficacious agents as front-line treatment to maximize outcomes for patients, and as such, VELCADE will be a leading therapy in this disease setting."
Frontline VMP in Elderly Multiple Myeloma Patients: Extended Follow-Up (Abstract #PO-718)
"The addition of VELCADE has produced the best complete remisssion and three-year survival rates ever reported with a melphalan prednisone therapy, providing results that are as powerful as stem cell transplantation without the associated side effects, recovery time and expense," said Maria-Victoria Mateos, M.D., Ph.D., Grupo Espanol de Multiple Myeloma. "With VELCADE added to this combination, we now are able to offer all patients, including those who historically could not have a transplant, an alternative that provides complete remission and prolongs lives."
The Phase I / II study evaluated efficacy and safety of VMP combination therapy in untreated MM patients aged 65 years or older with a median age of 75 years. The study included 54 evaluable patients ineligible for SCT. Patients received VELCADE at 1.0 mg/m(2) or 1.3 mg/m(2) on days 1, 4, 8, 11, 22, 25, 29 and 32 for four six-week cycles, then on days 1, 8, 15 and 22 for five five-week cycles. Patients also received melphalan at 9 mg/m(2) and prednisone at 60 mg/m(2) on days 1 through 4 of each cycle. Response was assessed using the European Group for Blood and Marrow Transplant (EBMT) criteria. Results were presented by Dr. Mateos and showed a CR rate of 43 percent. At 38 months, 85 percent of patients were alive. Side effects were predictable and manageable, similar to those seen in previous VELCADE clinical trials.
Long Term Follow-Up of VcAD (or PAD) for Untreated Multiple Myeloma (Abstract #PO-725)
The open-label Phase I / II study investigated the efficacy of VcAD combination therapy in untreated MM patients. The trial included 40 evaluable patients, who were treated for four cycles prior to SCT. Patients received either VELCADE at 1.3 mg/m(2) (VcAD-1) or 1.0 mg/m(2) (VcAD-2) on days 1, 4, 8 and 11 of a 21-day schedule. Patients also received doxorubicin at 9 mg/m(2) on days 1 through 4 and dexamethasone at 40 mg on days 1 through 4, 8 through 11, and 15 through 18 during cycle one and on days 1 through 4 during cycles two through four. Responses were classified using the EBMT criteria. Results were presented by Rakesh Popat, M.D., St. Bartholomew's Hospital, and showed in the VcAD-1 arm a CR rate of 29 percent prior to SCT, which improved to 57 percent following SCT. At one year, 100 percent of patients were alive with 95 percent of patients alive at two years. Median OS has not yet been reached after four years. Side effects, including peripheral neuropathy, were predictable and manageable, similar to those seen in previous VELCADE clinical trials.
Combination Therapy with VELCADE, DOXIL and Dexamethasone in Newly Diagnosed Myeloma: Updated Results of a Phase II Clinical Trial (Abstract #PO- 721)
The Phase II trial evaluated the efficacy of VDD combination therapy in untreated MM patients. The trial enrolled 40 patients, who received VELCADE at 1.3 mg/m(2) on days 1, 4, 8 and 11 of a 21-day schedule. Patients also received DOXIL at 30 mg/m(2) on day 4 and dexamethasone at 40 mg on days 1 through 4 or 20 mg corresponding with the VELCADE schedule. After four cycles of VDD, patients proceeded to SCT or continued VDD maintenance therapy. Responses were determined based on the EBMT criteria. Results were presented by Andrzej Jakubowiak, M.D., Ph.D., University of Michigan Comprehensive Cancer Center, and demonstrated a CR rate of 43 percent prior to SCT, which improved to 65 percent following SCT. At 16 months, 100 percent of patients were alive. Side effects were predictable and manageable, similar to those seen in previous VELCADE clinical trials.
Phase I / II Study of Upfront VELCADE, Lenalidomide and Dexamethasone in Multiple Myeloma: Early Results (Abstract #PO-715)
This Phase I / II study of VRD combination therapy was designed to determine the maximum tolerated dose (MTD) and efficacy in untreated MM patients. The preliminary analysis included 15 evaluable patients, who received VELCADE at 1.0 mg/m(2) or 1.3 mg/m(2) 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 mg corresponding with the VELCADE schedule. Patients were treated for up to eight cycles at four planned dose levels. MTD has not yet been reached. Response was assessed by modified EBMT criteria. Results were presented by Paul Richardson, M.D., Dana-Farber Cancer Institute, and showed an ORR (CR + partial response + minor response) of 100 percent, including a CR rate of 20 percent. Side effects were manageable and included hypophosphatemia, infections and thrombocytopenia. No grade 3 or higher 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 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 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. 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).
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) Complete remission / complete response includes both immunofixation positive and negative readouts
Source: Millennium Pharmaceuticals
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