As we develop important new medicines to treat cancer, Millennium seeks to continuously demonstrate our ethical, clinical and scientific good intentions to the public. We believe that patients, family members, health professionals and members of the public should have access to medically important information on Millennium clinical research. Clinical Trial Enrollment

For information about enrolling patients in Millennium-sponsored clinical trials of investigational and marketed oncology drugs, please call 800-589-9005.

Millennium notifies the public of the start of all Company-sponsored Phase I, II, III and IV clinical trials designed to test the safety or efficacy, or both of Millennium investigational and marketed oncology drugs on www.clinicaltrials.gov, a National Institute of Health registry (a list) of ongoing clinical trials. This notification reflects the Company's commitment to provide patients and physicians with a list of ongoing clinical trials. Clinical Trial Results

Millennium publishes results of completed, Phase II, III, and IV clinical trials of its marketed product, VELCADE® (bortezomib) for Injection, in a timely, objective, accurate, and balanced manner – regardless of outcome. When these trial results are published in a peer-reviewed journal, Millennium will post a citation (and, where possible, a link) to the journal article on www.clinicalstudyresults.org, a central, widely accessible clinical trials results database and the trial results on www.clinicaltrials.gov. The publication of these results is consistent with Millennium's Core Values and applicable laws, regulations, and guidelines regarding disclosure of clinical trial results including the Principles on Conduct of Clinical Trials and Communication of Clinical Trial Results promulgated by the Pharmaceutical Research and Manufacturers of America (PhRMA).

INDICATIONS: CONTRAINDICATIONS: VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol.

WARNINGS AND PRECAUTIONS:
VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic therapy. Complete blood counts (CBC) should be monitored frequently during treatment with VELCADE.

Pregnancy Category D: Women of childbearing potential should avoid becoming pregnant while being treated with VELCADE.

Peripheral Neuropathy: VELCADE treatment causes a peripheral neuropathy that is predominantly sensory. However, cases of severe sensory and motor peripheral neuropathy have been reported. Patients with pre-existing symptoms (numbness, pain or a burning feeling in the feet or hands) and/or signs of peripheral neuropathy may experience worsening peripheral neuropathy (including ≥Grade 3) during treatment with VELCADE. Patients should be monitored for symptoms of neuropathy, such as a burning sensation, hyperesthesia, hypoesthesia, paresthesia, discomfort, neuropathic pain or weakness. Patients experiencing new or worsening peripheral neuropathy may require change in the dose and schedule of VELCADE. The long-term outcome of peripheral neuropathy has not been studied in mantle cell lymphoma.

Hypotension: Hypotension (postural, orthostatic, and hypotension NOS) has been observed throughout therapy. Caution should be used when treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated.

Cardiac Disorders: Acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported, including reports in patients with no risk factors for decreased left ventricular ejection fraction. Patients with risk factors for, or who have existing heart disease should be closely monitored. There have been isolated cases of QT-interval prolongation in clinical studies; causality has not been established.

Pulmonary Disorders: 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 (ARDS) in patients receiving VELCADE. Some of these events have been fatal. There have been reports of pulmonary hypertension associated with VELCADE administration in the absence of left heart failure or significant pulmonary disease.

Reversible Posterior Leukoencephalopathy Syndrome (RPLS): There have been 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.

Gastrointestinal Adverse Events: VELCADE treatment can cause nausea, diarrhea, constipation, and vomiting sometimes requiring use of antiemetic and antidiarrheal medications. Ileus can occur. Fluid and electrolyte replacement should be administered to prevent dehydration.

Thrombocytopenia/Neutropenia: VELCADE is associated with thrombocytopenia and neutropenia. Platelet counts should be monitored prior to each dose of VELCADE. Patients experiencing thrombocytopenia may require change in the dose and schedule of VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage in association with VELCADE. Transfusions may be considered.

Tumor Lysis Syndrome: Because VELCADE is a cytotoxic agent and can rapidly kill malignant cells, the complications of tumor lysis syndrome may occur.

Hepatic Events: Cases of acute liver failure have been reported in patients receiving multiple concomitant medications and with serious underlying medical conditions.

Patients with Hepatic Impairment: VELCADE exposure is increased in patients with moderate or severe hepatic impairment. These patients should be treated with VELCADE at reduced starting doses and closely monitored for toxicities.

ADVERSE EVENT DATA:

DRUG INTERACTIONS: 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.

USE IN SPECIFIC POPULATIONS:
Nursing Mothers: It is not known whether bortezomib is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from VELCADE, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use: The safety and effectiveness of VELCADE in children has not been established.

Patients with Renal Impairment: Dosing adjustments of VELCADE are not necessary for patients with renal insufficiency. In patients undergoing dialysis, VELCADE should be administered after the dialysis procedure.

Patients with Diabetes: During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.

Effective as of 15 Jun 09

Please see the full prescribing information for VELCADE including warnings and precautions.