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Millennium: The Takeda Oncology Company Withdraws Cancer Drug Application Velcade  
10/6/2011 9:06:52 AM

CAMBRIDGE, Mass., Oct 06, 2011 (BUSINESS WIRE) -- Millennium: The Takeda Oncology Company with its parent company Takeda Pharmaceutical Company Limited today announced that it is withdrawing the supplemental new drug application (sNDA) for the use of VELCADE(R) (bortezomib) for Injection in combination with rituximab in patients with relapsed follicular lymphoma. The LYM-3001 pivotal clinical trial findings were presented at the American Society of Hematology meeting in 2010 and published in the Lancet Oncology in July 2011. The addition of VELCADE to rituximab demonstrated a 1.8-month improvement in median progression-free survival (PFS) compared with rituximab alone (HR=0.822; P=0.039). Upon further evaluation based upon discussions with external advisors and the U.S. Food and Drug Administration (FDA), the Company has made a business decision to withdraw the application.

The LYM-3001 trial randomized 676 patients with relapsed follicular lymphoma to receive VELCADE and rituximab or rituximab alone. The primary endpoint of the trial was progression-free survival. The most common adverse events of grade 3 or higher were neutropenia (11 percent in the VELCADE-rituximab arm and 4 percent in the rituximab arm), infection (11 percent and 4 percent, respectively), diarrhea (7 percent and 0 percent, respectively) and herpes zoster (4 percent and <1 percent, respectively), nausea or vomiting (3 percent and <1 percent, respectively) and thrombocytopenia (3 percent and <1 percent, respectively).

VELCADE is approved in the United States for use in patients with multiple myeloma and for the treatment of patients with mantle cell lymphoma who have received at least one prior therapy. Millennium's clinical development program for VELCADE in non-Hodgkin lymphoma includes ongoing trials in previously untreated mantle cell lymphoma and diffuse large B-cell lymphoma. In follicular lymphoma, Millennium continues to support evaluation of VELCADE in various patient subgroups.

About VELCADE

VELCADE is co-developed by Millennium and Ortho Biotech Oncology Research & Development, unit of Johnson & Johnson Pharmaceutical Research & Development, L.L.C. Millennium is responsible for commercialization of VELCADE in the U.S., Janssen-Cilag International N.V. is responsible for commercialization in Europe and the rest of the world. Takeda Pharmaceutical Company Limited and Janssen Pharmaceutical K.K. co-promote VELCADE in Japan. VELCADE is approved in more than 90 countries and has been used to treat more than 300,000 patients worldwide.

Important Safety Information

CONTRAINDICATION

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 greater-than or equal to 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.

Adverse Reactions

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).

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, http://www.millennium.com/ .

About Takeda

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 .

SOURCE: Millennium: The Takeda Oncology Company

Millennium

Manisha Pai, +1-617-551-7877

Manisha.pai@mpi.com

or

David Albaugh, +1-617-444-4457

david.albaugh@mpi.com

or

Takeda Pharmaceutical Company Limited

Corporate Communications Dept. (PR/IR)

+81-3-3278-2037


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