Millennium Initiates First Clinical Trial with the First Oral Proteasome Inhibitor.
-- Company advances protein homeostasis program--
CAMBRIDGE, Mass. -- Millennium: The Takeda Oncology Company today announced it has further expanded its protein homeostasis program with the initiation of a Phase I clinical trial Noun 1. phase I clinical trial - a clinical trial on a few persons to determine the safety of a new drug or invasive medical device; for drugs, dosage or toxicity limits should be obtained
phase I for an oral formulation of MLN9708, the Company's second-generation proteasome inhibitor. An intravenous formulation of MLN9708 entered clinical trials in March.
MLN9708 is the third molecule Millennium has developed from its innovative research in protein homeostasis. VELCADE([R]) (bortezomib) for Injection, the first-in-class proteasome inhibitor developed by Millennium, is currently approved for patients with multiple myeloma, and patients with mantle cell lymphoma Mantle cell lymphoma (MCL) is one of the rarer of the non-Hodgkin's lymphomas, comprising about 6% of NHL cases. There are only about 15,000 patients presently in the U.S. (The incidence seems to be somewhat higher in Europe. who have received at least one prior therapy. It is the only proteasome inhibitor on the market today. Last year, Millennium initiated Phase I clinical trials of MLN4924, which targets the Millennium discovered Nedd8-Activating Enzyme (NAE), located upstream of the proteasome in the Ubiquitin Proteasome Pathway (UPP). The discovery of MLN4924 was recently published in the journal Nature in April 2009.
Millennium will continue its research and development activities in protein homeostasis, which has been shown to be linked to the pathologic properties of a broad range of cancers. The advancement of the oral formulation of MLN9708 is the latest example of the Company moving this program forward based on its expertise in this unique area of cancer biology.
"We are thrilled that both MLN9708 and MLN4924, two novel agents from our oncology pipeline, have advanced to the clinic," said Joseph B. Bolen, Ph.D., Chief Scientific Officer, Millennium. "These milestones, in addition to our ongoing collaborative research agreement with Harvard Medical School Harvard Medical School (HMS) is one of the graduate schools of Harvard University. It is a prestigious American medical school located in the Longwood Medical Area of the Mission Hill neighborhood of Boston, Massachusetts. , further underscore our significant expertise and commitment to the field of protein homeostasis."
Millennium and Harvard Medical School's Office of Technology Development announced an innovative collaborative agreement in January 2008 to pursue a research program in the area of protein homeostasis. Under the terms of the agreement, Harvard has granted Millennium a license to certain inventions from the laboratory of Professor J. Wade Harper. The two institutions are working jointly to advance the program in this new area of research over several years under a sponsored research agreement.
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
About Harvard University's Office of Technology Development
The Harvard Office of Technology Development (OTD) is responsible for all activities pertaining to the evaluation, patenting and licensing of new inventions and discoveries made at Harvard University and Harvard Medical School. OTD also serves to further the development of Harvard technologies through the establishment of sponsored research collaborations with industry. OTD's mission is to promote the public good by fostering innovation and translating new inventions made at Harvard into useful products available and beneficial to society.
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 mannitol /man·ni·tol/ (man´i-tol) a sugar alcohol formed by reduction of mannose or fructose and widely distributed in plants and fungi; an osmotic diuretic used to prevent and treat acute renal failure, to promote excretion of toxic . VELCADE should be administered under the supervision of a physician experienced in the use of antineoplastic antineoplastic /an·ti·neo·plas·tic/ (-ne?o-plas´tik)
1. inhibiting or preventing development of neoplasms; checking maturation and proliferation of malignant cells.
2. an agent that so acts. 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 tumor lysis syndrome
A syndrome characterized by abnormally high levels of phosphates, potassium, and uric acid and by abnormally low levels of calcium in the blood following induction chemotherapy of malignant tumors, possibly caused by the release 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 congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time. , 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 pneumonitis /pneu·mo·ni·tis/ (noo?mo-ni´tis) inflammation of the lung; see also pneumonia.
hypersensitivity pneumonitis , interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome acute respiratory distress syndrome
See adult 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 Acute liver failure is the appearance of severe complications rapidly after the first signs of liver disease (such as jaundice), and indicates that the liver has sustained severe damage (loss of function of 80-90% of liver cells). 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([R]) [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 asthenic (asthēn´ik),
adj describing an individual with a long, slender appearance who is thin and flat-chested and has long limbs and a short trunk; comparable to the ectomorph in Sheldon's classification. 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 pyrexia /py·rex·ia/ (pi-rek´se-ah) pl. pyrex´iae fever.pyrex´ial
py·rex (34%), vomiting (33%), anemia (29%), edema (23%), headache, paresthesia paresthesia /par·es·the·sia/ (par?es-the´zhah) morbid or perverted sensation; an abnormal sensation, as burning, prickling, formication, etc.
par·es·the·sia or par·aes·the·sia
n. 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 upper respiratory tract infection URI Infectious disease A nonspecific term used to describe acute infections involving the nose, paranasal sinuses, pharynx, and larynx, the prototypic URI is the common cold; flu/influenza is a systemic illness involving the URT , 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%).
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).
Editors' Note: This press release is also available under the Media section of the Company's website at: www.millennium.com