CAMBRIDGE, Mass. & OSAKA, Japan--(Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited (TSE:4502) today announced that it has submitted two supplemental new drug applications (sNDAs) for VELCADE® (bortezomib) for Injection to the U.S. Food and Drug Administration (FDA). The first application seeks to add a subcutaneous route of administration for VELCADE. The second application is for the use of VELCADE in combination with rituximab in patients with relapsed follicular non-Hodgkin lymphoma (NHL).)--
“We look forward to working with the FDA on both of these submissions.”
“These two applications represent our continued commitment to further the clinical understanding of VELCADE by enhancing its administration options as well as defining its utility in new cancers,” said Nancy Simonian, M.D., Chief Medical Officer, Millennium. “We look forward to working with the FDA on both of these submissions.”
Both supplements are based on results from clinical trials that were presented at the American Society of Hematology (ASH) annual meeting held December 4-7, 2010, in Orlando, Florida. The VELCADE subcutaneous pivotal trial findings were published in the online version of the Lancet Oncology on April 19.
VELCADE is currently approved for intravenous use only in patients with multiple myeloma and in patients with mantle cell lymphoma who have received at least one prior therapy, a sub-type of NHL. VELCADE has been used by more than 230,000 patients in more than 90 countries worldwide.
VELCADE is co-developed by Millennium and Ortho Biotech Oncology Research & Development, a unit of 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. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. entered into a co-promote agreement in May 2010 for VELCADE in Japan. VELCADE is approved in more than 90 countries and has been used to treat more than 230,000 patients worldwide.
Important Safety Information
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 and Nursing: Women should avoid breastfeeding or becoming pregnant while being treated with VELCADE.
Peripheral neuropathy, including severe cases, may occur – manage with dose modification or discontinuation. Patients with pre-existing symptoms may experience worsening peripheral neuropathy (including ≥ Grade 3). Patients should be monitored for symptoms of peripheral neuropathy.
Hypotension can occur. Caution should be used when treating patients receiving antihypertensives, those with a history of syncope and those who are dehydrated.
Cardiac Disorders including acute development or exacerbation of congestive heart failure and new onset of decreased left ventricular ejection fraction have been reported. Isolated cases of QT-interval prolongation have been reported. Patients with risk factors for, or existing heart disease should be closely monitored.
Pulmonary Disorders, some fatal, including pneumonitis interstitial pneumonia, lung infiltration and Acute Respiratory Distress Syndrome (ARDS), have been reported. Pulmonary hypertension in the absence of left heart failure or significant pulmonary disease has also been reported.
Gastrointestinal Adverse Events including nausea, diarrhea, constipation, and vomiting have occurred and may require use of antiemetic and antidiarrheal medications or fluid replacement.
Thrombocytopenia/Neutropenia can occur – manage with dose and/or schedule modifications. Platelets should be monitored prior to each dose of VELCADE. There have been reports of gastrointestinal and intracerebral hemorrhage. Transfusions may be considered.
Patients with Hepatic Impairment: VELCADE exposure is increased in patients with moderate or severe hepatic impairment. These patients should be started at a lower dose of VELCADE, which can be adjusted after cycle 1 depending on tolerability.
Patients with Diabetes: Hypoglycermia and hyperglycemia have been reported with VELCADE use. Patients may require close monitoring and adjustment of the antidiabetic medications.
Tumor Lysis Syndrome, Reversible Posterior Leukoencephalopathy Syndrome (RPLS) and acute hepatic failure have been reported.
Previously Untreated MM: In the phase 3 VELCADE with melphalan and prednisone study, the most commonly reported adverse events 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%).
Relapsed MM and MCL: In the integrated analysis of 1163 patients in phase 2 and 3 studies, 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%).
In the integrated analysis, a total of 50% of patients experienced serious adverse events (SAEs). 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).
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.
Located in Osaka, Japan, Takeda is a research-based global company with its main focus on pharmaceuticals. As the largest pharmaceutical company in Japan and one of the global leaders of the industry, Takeda is committed to strive towards better health for patients worldwide through leading innovation in medicine. Additional information about Takeda is available through its corporate website, www.takeda.com.
Editors’ Note: This press release is also available under the Media section of the Company’s website at: http://www.millennium.com/media.