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Publications Feature Bortezomib for Injection Strength in Hematological Cancers

High complete response rate in front-line multiple myeloma- -Clinical benefits in relapsed / refractory multiple myeloma accompanied by advanced renal failure

High level of response in newly diagnosed and previously treated mantle cell lymphoma-

CAMBRIDGE, MA -- December 4, 2006 -- Millennium Pharmaceuticals, Inc. today announced the publication of clinical data of Velcade in the treatment of newly diagnosed multiple myeloma (MM), MM accompanied by advanced renal failure, and mantle cell lymphoma (MCL). These data underscore the substantial activity and well-characterized safety profile of Velcade in the treatment of hematological cancers.

"Velcade, as a single agent and in combination, continues to be differentiated by consistently demonstrating high response rates, including complete responses, in a broad range of patients including those who until now had limited treatment options," says Bob Tepper, MD, President, Research and Development, Millennium. "Several recent publications have highlighted this Velcade strength. We continue to advance our Phase III clinical and regulatory programs in front-line multiple myeloma and non-Hodgkin's lymphoma with the goal of rapidly bringing this novel therapy to broader patient groups."

Velcade Combination Shows High Complete Response Rate in Newly Diagnosed Multiple Myeloma Patients
In the November 2006 issue of Haematologica Journal, results of a phase 2 study showed a complete response (CR) and near complete response (nCR) rate of 21% after four cycles of induction therapy with Velcade plus dexamethasone.

Along with a previously published study by Sundar Jagannath, MD, of St. Vincent's Comprehensive Cancer Center, these data are among the highest recorded CR/nCR rates for a dexamethasone-based therapy in the treatment of front-line multiple myeloma. In previous clinical trials, Velcade in combination with other commonly used therapies has shown an overall response rate (ORR) of up to 95% and a CR/nCR rate of up to 43% in the front-line MM setting.

The open-label, multicenter study conducted by Intergroupe Francophone du Myelome (IFM) investigated the efficacy and safety of Velcade in combination with dexamethasone as induction therapy prior to stem cell transplantation in 48 evaluable patients with newly diagnosed MM eligible for stem cell transplantation. Patients who received the combination achieved an ORR of 67%. In the 42 patients who went on to stem cell collection, all patients were able to proceed to transplant. Therapy was well tolerated. The most common side effects were gastrointestinal symptoms, peripheral neuropathy and fatigue.

A Phase 3 registration-enabling study of Velcade in combination with dexamethasone compared to vincristine, doxorubicin, and dexamethasone (VAD), a conventional induction therapy, is ongoing. Preliminary data from this trial are expected to be presented by IFM at The American Society of Hematology 48th Annual Meeting, December 9-12, 2006. This trial is part of a broad Phase 3 program being conducted by Millennium and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. evaluating Velcade in the front-line multiple myeloma transplant and non-transplant treatment settings.

Velcade Based Therapies Show Benefits in Relapsed and / or Refractory Multiple Myeloma Patients with Advanced Renal Failure Requiring Dialysis
In the Blood First Edition Paper, prepublished online November 30, 2006, results of a retrospective analysis evaluating Velcade therapies in relapsed and / or refractory MM patients with advanced renal failure demonstrated an ORR of 75% with a CR/nCR rate of 30%. Approximately one-third of all MM patients experience some form of renal impairment during the course of their disease which significantly impacts prognosis and limits treatment options. The data from this analysis are consistent with previous reports showing the efficacy and safety of Velcade in patients with impaired renal function and support the use of Velcade therapies in patients requiring dialysis.

The retrospective analysis included 20 evaluable MM patients requiring dialysis for advanced renal failure. Twenty-nine percent of patients received Velcade in combination with liposomal doxorubicin and thalidomide while the remaining received Velcade either alone or as combination therapy with dexamethasone, thalidomide, doxorubicin, cyclophosphamide and / or prednisone. Patients stayed on treatment for a median of five cycles at the standard Velcade dose with a mean of seven cycles which is comparable to the duration of treatment reported in MM patients with normal renal function. Median duration of CR was 15 months while the median duration of PR was 4.5 months. A total of four patients had improved renal function following Velcade based therapy, including one patient who was spared from dialysis after rapid response to treatment and three other patients who became independent of dialysis.

Treatment was well tolerated. Common adverse events were similar to those seen in previous phase 2 and 3 studies of patients with relapsed and / or refractory MM.

Velcade Shows High Level of Response in Treatment of Newly Diagnosed and Previously Treated Mantle Cell Lymphoma Patients
In the September 13, 2006 issue of Annals of Oncology, results of a phase 2 study of single-agent Velcade showed an ORR of 46% in patients with mantle cell lymphoma. Median response duration was 10 months. The ORR for newly diagnosed patients was 46%, similar to that observed in previously treated patients.

The response rate in previously treated patients support the results of several published trials of Velcade in relapsed mantle cell lymphoma, including the multi-center, international PINNACLE study, the largest to date in relapsed MCL. These trials showed that Velcade as a single agent had substantial activity with an ORR in the range of 30 to 40% and a CR rate up to 21%. Velcade is currently under Priority Review with the U.S. Food and Drug Administration for relapsed mantle cell lymphoma. A decision is expected by December 9, 2006. The significant response rate in newly diagnosed patients is the first published data of Velcade in this setting and demonstrates the potential of Velcade across all lines of therapy in mantle cell lymphoma. Trials of Velcade in combination are being conducted by cooperative groups in newly diagnosed mantle cell lymphoma.

The study mentioned in this publication, conducted by the National Cancer Institute of Canada Clinical Trials Group, enrolled 29 patients, including 13 who had not received prior chemotherapy. Side effects included neurological toxicity and myalgia.

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 increasing incidence and 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.(1)

About Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma
Non-Hodgkin's lymphoma (NHL) is the most common hematological cancer, the fifth leading cause of cancer death and the second fastest growing form of cancer in the U.S.(2) The prevalence of NHL is approximately 400,000 patients, 77,000 patients with follicular lymphoma and 10,000 with mantle cell lymphoma. There are approximately 54,000 new cases of NHL diagnosed per year, and 19,000 deaths are attributed to the disease annually.(3,4)

Mantle cell lymphoma is an aggressive, rapidly progressive subtype of NHL, and is not curable with standard treatment. Because there is no generally accepted treatment approach and options often are limited, there is a need for new therapies. The average life expectancy for a patient with relapsed mantle cell lymphoma is one year.

About Velcade
Velcade is the market leader in relapsed multiple myeloma with over 44,000 patients treated worldwide, including clinical trials. Velcade is being co- developed by Millennium Pharmaceuticals, Inc. and Johnson & Johnson Pharmaceutical Research & Development, L.L.C. (J&JPRD). 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 75 countries worldwide. Velcade also is approved in the European Union as a treatment at first relapse.

Velcade is indicated for the treatment of multiple myeloma patients 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.

In 331 patients who were treated with Velcade in a Phase III study, the most commonly reported adverse events were asthenic conditions (61%), diarrhea (57%), nausea (57%), constipation (42%), peripheral neuropathy (36%), vomiting (35%), pyrexia (35%), thrombocytopenia (35%), psychiatric disorders (35%), anorexia and appetite decreased (34%), parasthesia (27%), dysesthesia (27%), anemia and headache (26%), and cough (21%). Fourteen% of patients reported at least one episode of grade 4 toxicity; the most common grade 4 toxicities were thrombocytopenia (4%), neutropenia (2%), and hypercalcemia (2%). A total of 144 patients on Velcade (44%) reported serious adverse events (SAEs) during the study. The most commonly reported SAEs were pyrexia (6%), diarrhea (5%), dyspnea and pneumonia (4%), and vomiting (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).

REFERENCES:
1. American Cancer Society, Overview: Multiple Myeloma, 2005, http://www.cancer.org.
2. American Cancer Society, Inc., Surveillance Research, 2005.
3. SEER, SARGA, and Decision Resources (for growth rate) data.
4. Federico et al., BLOOD 95(3): 783-789; 2000.


SOURCE: Millennium Pharmaceuticals, Inc.

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