Velcade (Bortezomib) for Injection and Pipeline Data to Be Highlighted at American Society of Clinical Oncology Annual Meeting

-- Data focus on VELCADE based combinations, investigational oncology molecules --

CAMBRIDGE, Mass.--(BUSINESS WIRE)--May 19, 2009 - Millennium: The Takeda Oncology Company today announced that more than 49 oral and poster presentations featuring VELCADE and the Company's pipeline molecules will be presented at the American Society of Clinical Oncology (ASCO) Annual Meeting being held in Orlando, Florida, May 29 – June 2, 2009. These data include two oral presentations on studies examining the use of VELCADE based combinations in patients with previously untreated multiple myeloma (MM), and one poster on the use of a VELCADE based combination in patients with relapsed or refractory follicular lymphoma. Clinical and preclinical data also will be presented on three Millennium oncology pipeline products, including MLN8237, an oral compound designed to selectively inhibit Aurora A kinase, discovered and developed by Millennium scientists; and MLN4924, a small molecule aimed at inhibiting the NEDD8-Activating Enzyme (NAE), a Millennium discovered target.

“The volume of data being presented at this year's ASCO meeting shows that VELCADE continues to be an important component of ongoing clinical research in hematologic malignancies,” said Nancy Simonian, M.D., Chief Medical Officer, Millennium. “Additionally, the early clinical data on our investigational oncology compounds support the potential of novel pathways that may advance oncology research.”

VELCADE Data

A total of 42 abstracts on VELCADE were accepted for publication or presentation, and emerging clinical data to be featured at ASCO include VELCADE based combinations in both transplant and non-transplant eligible previously untreated MM patients. Additional presentations will highlight data from clinical trials evaluating the use of VELCADE in relapsed or refractory follicular lymphoma, relapsed or refractory mantle cell lymphoma as well as solid tumors. Presentation highlights are scheduled to include:

  • A Phase III study of VMPT versus VMP in newly diagnosed elderly myeloma patients
    • Lead investigator: Antonio Palumbo, M.D., University of Torino and Italian Multiple Myeloma Study Group, Torino, Italy
    • Abstract #8515: Oral presentation session: Sunday, May 31, 9:00 a.m. ET
  • Lenalidomide, Bortezomib, Doxil® and Dexamethasone in Newly Diagnosed Multiple Myeloma: Initial Results of Phase I/II Multiple Myeloma Research Consortium Trial
    • Lead investigator: Andrzej Jakubowiak, M.D., Ph.D., Associate Professor, Department of Hematology/Oncology, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan
    • Abstract #8517: Oral presentation session: Sunday, May 31, 9:30 a.m. ET
  • Bortezomib (V), bendamustine (B), and rituximab (R) in patients (pts) with relapsed (rel) or refractory (ref) follicular lymphoma (FL): dose finding results of the VERTICAL study
    • Lead investigator: Jeffrey Matous, M.D., Associate Clinical Professor, Department of Medicine, University of Colorado Health Sciences Center
    • Abstract #8550: Poster session: Saturday, May 30, 8:00 a.m. ET

Other Oncology Data

Additional presentations at ASCO will include data on investigational molecules in the Company's expanded oncology pipeline. MLN8237 is an oral compound designed to selectively inhibit Aurora A kinase and was discovered and developed by Millennium scientists. Millennium initiated Phase II trials of the compound in March 2009 for the potential treatment of patients with hematologic malignancies; a Phase II trial in patients with ovarian cancer began in April 2009.

Data also will be presented on MLN4924, a small molecule designed to inhibit NAE, a Millennium discovered target upstream of the proteasome. Data providing the preclinical rationale for the advancement of the molecule into clinical trials were recently published in the journal Nature. MLN4924 is currently in Phase I clinical trials evaluating its use in the treatment of patients with both solid tumors and hematologic malignancies. Key presentations are scheduled to include:

  • Phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of MLN8237, a novel selective Aurora A kinase (AAK) inhibitor, in patients (pts) with advanced solid tumors
    • Lead investigator: Andres Cervantes-Ruiperez, M.D., Ph.D., Servicio Oncologia Medica, Hospital Clinical Universitario Valencia
    • Abstract #2565: Poster session: Saturday, May 30, 8:00 a.m. ET
  • Effect of Aurora A kinase inhibitor MLN8237 combined with rituximab on antitumor activity in preclinical B-cell non-Hodgkin's lymphoma models
    • Lead investigator: Mengkung Zhang, M.D., Millennium: The Takeda Oncology Company
    • Abstract #8553: Poster session: Saturday, May 30, 8:00 a.m. ET
  • MLN4924, a novel NAE inhibitor, induces pharmacodynamic changes in blood and skin
    • Lead investigator: John Kauh, M.D., Assistant Professor of Hematology and Oncology, The Emory Clinic, Emory University Hospital
    • Abstract #2562: Poster session: Saturday, May 30, 8:00 a.m. ET

About VELCADE

VELCADE is 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. VELCADE is approved in more than 87 countries worldwide.

Important Safety Information

In the U.S., VELCADE is indicated for the treatment of patients with multiple myeloma. VELCADE also 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.

Risks associated with VELCADE therapy include new or worsening peripheral neuropathy, hypotension throughout therapy, cardiac and pulmonary disorders, reversible posterior leukoencephalopathy syndrome, gastrointestinal adverse events, thrombocytopenia, neutropenia, tumor lysis syndrome and hepatic events. Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE. Nursing mothers are advised not to breastfeed while receiving 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 new onset of decreased left ventricular ejection fraction has been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. There have been 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. There have been 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. Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions. Patients who are concomitantly receiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy. Patients on oral antidiabetic medication while receiving VELCADE should check blood sugar levels frequently.

Adverse Reaction 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 previously treated multiple myeloma (N=1008, not including the Phase III, VELCADE plus DOXIL® [doxorubicin HCl liposome injection] study) and previously treated 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%), anemia (29%), edema (23%), headache, paresthesia and dysesthesia and headache (each 22%), dyspnea (21%), cough and insomnia (each 20%), rash (18%), arthralgia (17%), neutropenia and dizziness (excluding vertigo) (each 17%), pain in limb and abdominal pain (each 15%), bone pain (14%), back pain and hypotension (each 13%), herpes zoster, nasopharyngitis, upper respiratory tract infection, myalgia and pneumonia (each 12%), muscle cramps (11%), and dehydration and anxiety (each 10%). 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%).

In the Phase III VELCADE + melphalan and prednisone study, the safety profile of VELCADE in combination with melphalan/prednisone is consistent with the known safety profiles of both VELCADE and melphalan/prednisone. The most commonly reported adverse events for VELCADE in combination with MP vs MP, respectively, were thrombocytopenia (52% vs 47%), neutropenia (49% vs 46%), nausea (48% vs 28%), peripheral neuropathy (47% vs 5%), diarrhea (46% vs 17%), anemia (43% vs 55%), constipation (37% vs 16%), neuralgia (36% vs 1%), leukopenia (33% vs 30%), vomiting (33% vs 16%), pyrexia (29% vs 19%), fatigue (29% vs 26%), lymphopenia (24% vs 17%), anorexia (23% vs 10%), asthenia (21% vs 18%), cough (21% vs 13%), insomnia (20% vs 13%), edema peripheral (20% vs 10%), rash (19% vs 7%), back pain (17% vs 18%), pneumonia (16% vs 11%), dizziness (16% vs 11%), dyspnea (15% vs 13%), headache (14% vs 10%), pain in extremity (14% vs 9%), abdominal pain (14% vs 7%), paresthesia (13% vs 4%), herpes zoster (13% vs 4%), bronchitis (13% vs 8%), hypokalemia (13% vs 7%), hypertension (13% vs 7%), abdominal pain upper (12% vs 9%), hypotension (12% vs 3%), dyspepsia (11% vs 7%), nasopharyngitis (11% vs 8%), bone pain (11% vs 10%), arthralgia (11% vs 15%) and pruritus (10% vs 5%).

About Millennium

Millennium: The Takeda Oncology Company, a leading biopharmaceutical company based in Cambridge, Mass., markets VELCADE, a first-in-class proteasome inhibitor, and has a robust clinical development pipeline of product candidates. Millennium Pharmaceuticals, Inc. was acquired by Takeda Pharmaceutical Company Ltd. in May, 2008. The Company's research, development and commercialization activities are focused in oncology. Additional information about Millennium is available through its website, www.millennium.com.

Editors' Note: This press release is also available under the Media section of the Company's website at: www.millennium.com.

Contact: Millennium: The Takeda Oncology Company
Manisha Pai, 617-551-7877
Manisha.Pai@mpi.com
or
Karen Gobler, 617-444-1392
Karen.Gobler@mpi.com

Posted: May 2009

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