Millennium Initiates Clinical Trial To EVOLVE The Treatment Of Patients With Newly Diagnosed Multiple Myeloma

Main Category: Lymphoma / Leukemia / Myeloma
Also Included In: Cancer / Oncology;  Clinical Trials / Drug Trials
Article Date: 16 Aug 2007 - 0:00 PDT

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Millennium Pharmaceuticals, Inc. (Nasdaq: MLNM) today announced the initiation of a randomized, multi-center, Company-sponsored Phase II trial to evaluate the efficacy of combining VELCADE(R) (bortezomib) for Injection, lenalidomide / dexamethasone and cyclophosphamide in the front-line multiple myeloma (MM) setting. The trial, named EVOLUTION(1), will combine the highly active and noveltherapies of VELCADE and lenalidomide / dexamethasone and also explore the incremental benefit of cyclophosphamide, an alkylating agent, which in previous studies has shown synergistic activity with VELCADE.

"The objective of this trial is to evolve the treatment of multiple myeloma by combining these highly active therapies to induce early complete remission and improve long-term survival," said Nancy Simonian, M.D., Chief Medical Officer, Millennium. "We are exploring the potential of a new standard of care for patients with newly diagnosed multiple myeloma."

The EVOLUTION trial builds on positive results from previous studies of VELCADE in combination with these agents, showing some of the highest reported complete remission rates. This trial is expected to enroll approximately 100 patients, who will be randomized to either VELCADE, lenalidomide / dexamethasone or VELCADE, lenalidomide / dexamethasone and cyclophosphamide. The primary endpoint of the trial is complete response and very good partial response rates with secondary endpoints, including duration of response, overall survival, safety and tolerability.

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.

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. is co-promoting 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%).

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 otherwise.

(1) Evaluation of VELCADE, dexamethasOne, and Lenalidomide with or without cyclophosphamide Using Targeted Innovative ONcology strategies in the treatment of front-line multiple myeloma

Millennium Pharmaceuticals, Inc.
http://www.millennium.com