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Press release from Business Wire

Millennium and Seattle Genetics Initiate Global Phase 3 Clinical Trial of ADCETRIS® in Previously Untreated Advanced Hodgkin Lymphoma

<p class='bwalignc'> <b>− </b><i>First randomized clinical trial designed to examine the use of ADCETRIS as part of a frontline treatment regimen for patients with previously untreated classical Hodgkin lymphoma </i><b>−</b> </p>

Thursday, November 01, 2012

Millennium and Seattle Genetics Initiate Global Phase 3 Clinical Trial of ADCETRIS® in Previously Untreated Advanced Hodgkin Lymphoma08:00 EDT Thursday, November 01, 2012 CAMBRIDGE, Mass. & BOTHELL, Wash. (Business Wire) -- Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited (TSE:4502), and Seattle Genetics, Inc. (Nasdaq: SGEN) today announced the initiation of an international phase 3 clinical trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in patients with previously untreated advanced Hodgkin lymphoma (HL). The trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received scientific advice from the European Medicines Agency (EMA). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL. “Millennium is pleased to announce the initiation of the phase 3 trial of ADCETRIS in patients with previously untreated advanced Hodgkin lymphoma. This is a key step in our efforts to explore the potential of this targeted therapy as part of a frontline treatment regimen,” said Karen Ferrante, MD, Chief Medical Officer, Millennium. “The trial is part of our ongoing development program to explore patient populations that may benefit from treatment with ADCETRIS in earlier lines of therapy and in other CD30-expressing malignancies.” “There have been no new therapies approved for patients with newly diagnosed HL in many decades, representing a significant need to identify additional treatment options in this setting,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer, Seattle Genetics. “We believe through this novel ADCETRIS-containing regimen we have the potential to redefine the treatment of frontline HL. This trial is also an important part of our development plan for ADCETRIS, and may serve as confirmatory to our U.S. accelerated approval in relapsed HL and systemic anaplastic large cell lymphoma.” Study Design The randomized, open-label, phase 3 trial will investigate ADCETRIS+AVD1 versus ABVD2 as frontline therapy in patients with advanced classical HL. The primary endpoint is modified progression free survival (mPFS) per independent review facility assessment using the Revised Response Criteria for malignant lymphoma. Secondary endpoints include overall survival (OS), complete remission (CR) and safety. The multi-center trial will be conducted in North America, Europe, Latin America and Asia. The study will enroll approximately 1,040 eligible patients (approximately 520 patients per treatment arm) who have histologically-confirmed diagnosis of Stage III or IV classical HL who have not been previously treated with systemic chemotherapy or radiotherapy. For more information, please visit www.clinicaltrials.gov. About ADCETRIS® ADCETRIS (brentuximab vedotin) is an ADC comprising an anti-CD30 monoclonal antibody attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE), utilizing Seattle Genetics' proprietary technology. The ADC employs a linker system that is designed to be stable in the bloodstream but to release MMAE upon internalization into CD30-expressing tumor cells. ADCETRIS received accelerated approval from the U.S. Food and Drug Administration (FDA) in August 2011 for two indications: (1) the treatment of patients with Hodgkin lymphoma after failure of autologous stem cell transplant (ASCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not ASCT candidates, and (2) the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The indications for ADCETRIS are based on response rate. There are no data available demonstrating improvement in patient-reported outcomes or survival with ADCETRIS. See important safety information below. ADCETRIS is not approved for use outside the United States. The Marketing Authorization Application (MAA) for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), Ltd., was accepted for review by the European Medicines Agency (EMA) in June 2011. In July 2012, the Committee for Medicinal Products for Human Use (CHMP) of the EMA issued a positive opinion for the conditional marketing authorization of brentuximab vedotin for two indications. Seattle Genetics and Millennium are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs. About Hodgkin Lymphoma Lymphoma is a general term for a group of cancers that originate in the lymphatic system. There are two major categories of lymphoma: Hodgkin lymphoma and non-Hodgkin lymphoma. Hodgkin lymphoma is distinguished from other types of lymphoma by the presence of one characteristic type of cell, known as the Reed-Sternberg cell. The Reed-Sternberg cell generally expresses CD30. 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. About Seattle Genetics Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The U.S. Food and Drug Administration granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Agensys (an affiliate of Astellas), Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys and Genmab. More information can be found at www.seattlegenetics.com. U.S. Important Safety InformationBOXED WARNING Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS. Contraindication: Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity. Warnings and Precautions: Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly. Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted. Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS. Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken. Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed. Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy. Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus. Adverse Reactions: ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting. Drug Interactions: Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions. For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com. Certain of the statements made in this press release are forward looking, such as those, among others, relating to the therapeutic potential of ADCETRIS and initiation of future clinical trials. Actual results or developments may differ materially from those projected or implied in these forward-looking statements. Factors that may cause such a difference include the inability to show sufficient activity in the phase III trial and the risk of adverse events as ADCETRIS advances in clinical trials. In addition, data from our clinical trials, including our pivotal trials which were the basis for FDA accelerated approval, may not necessarily be indicative of subsequent clinical trial results. More information about the risks and uncertainties faced by Seattle Genetics is contained in the company's 10-Q for the quarter ended June 30, 2012 filed with the Securities and Exchange Commission. Seattle Genetics disclaims any intention or obligation to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise. 1 Adriamycin, vinblastine, dacarbazine 2 Adriamycin, bleomycin, vinblastine, dacarbazine Photos/Multimedia Gallery Available: http://www.businesswire.com/cgi-bin/mmg.cgi?eid=50455239&lang=en MillenniumLindsay Treadway, +1-617-444-3383lindsay.treadway@mpi.comorSeattle GeneticsInvestors:Peggy Pinkston, +1-425-527-4160ppinkston@seagen.comorMedia:Tricia Larson, +1-425-527-4180tlarson@seagen.com