Millennium and Seattle Genetics Initiate Global Phase 3 Trial of ADCETRIS™ in Patients with CD30-Expressing Relapsed Cutaneous T-cell Lymphoma

-Trial Conducted Under Special Protocol Assessment with FDA-

-Study Includes Evaluation of Companion Diagnostic Test for CD30 Identification-

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 pivotal phase 3 clinical trial evaluating ADCETRIS (brentuximab vedotin) in patients with CD30-expressing cutaneous T-cell lymphoma (CTCL) who received at least one prior systemic therapy. The global multi-center study with ADCETRIS, an antibody-drug conjugate (ADC) directed to CD30, will be conducted in the United States, Europe, Australia and Brazil. The trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) regarding the trial design. The study also received European Medicines Agency (EMA) scientific advice.

“Data from patients with cutaneous lesions observed in our pivotal trial in systemic anaplastic large cell lymphoma (sALCL) and interim data from investigator-sponsored trials in CTCL with ADCETRIS provide a strong rationale for initiating this phase 3 trial”

“Millennium is pleased to announce the initiation of the pivotal trial of ADCETRIS in patients with relapsed CD30-expressing CTCL. We recognize this as a significant milestone in our efforts to explore the potential of this targeted therapy in other indications,” said Karen Ferrante, MD, Chief Medical Officer, Millennium. “Looking forward, this study may support the potential to supplement therapeutic options for patients, from traditional systemic chemotherapy to ADCETRIS, a targeted therapy.”

“Data from patients with cutaneous lesions observed in our pivotal trial in systemic anaplastic large cell lymphoma (sALCL) and interim data from investigator-sponsored trials in CTCL with ADCETRIS provide a strong rationale for initiating this phase 3 trial,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer, Seattle Genetics. “CTCL is an important part of our development plan to broadly evaluate ADCETRIS in CD30-expressing malignancies. This trial complements many other ongoing and planned trials for patients in need, including two additional phase 3 trials for front-line Hodgkin lymphoma (HL) and front-line mature T-cell lymphomas expected to start by late 2012 or early 2013.”

CD30 is a member of the tumor necrosis factor receptor (TNFR) family and is a characteristic cell surface receptor for activated T-cells and B-cells, including the malignant cells of HL and sALCL. According to published literature, up to 50 percent of CTCL patients’ lesions express CD30^(1-3). Under a previously announced collaboration agreement with Ventana Medical Systems, Inc. (Ventana), Millennium and Seattle Genetics, Ventana is developing a molecular companion diagnostic test for use in this CTCL patient population.

Study design

The study is a randomized, open-label, phase 3 trial of ADCETRIS versus investigator’s choice of methotrexate or bexarotene in patients with CD30-positive CTCL, including those with primary cutaneous anaplastic large cell lymphoma (pcALCL) or mycosis fungoides (MF). The primary endpoint of the study is overall response rate (ORR), lasting at least 4 months, with ADCETRIS in patients with CD30-positive MF or pcALCL compared to that achieved with therapy in the control arm. The key secondary endpoints are complete response (CR), progression-free survival (PFS), and burden of symptoms. Approximately 124 patients will be enrolled in the pivotal trial.

For more information about the trial, 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^TM (brentuximab vedotin) received accelerated approval from the US FDA 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 (ALCL) 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.

ADCETRIS is not approved for the treatment of CTCL, front-line HL and front-line ALCL. ADCETRIS is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and systemic ALCL, filed by Takeda Global Research & Development Centre (Europe), was accepted for review by the European Medicines Agency for review in June 2011.

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 Cutaneous T-Cell Lymphoma

CTCLs constitute a group of non-Hodgkin lymphomas (NHLs) and are cancers of the T lymphocytes (a type of white blood cell) that mainly affect the skin but can also involve the blood, lymph nodes and/or internal organs in patients with advanced disease.

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, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at www.seattlegenetics.com.

U.S. Important Safety Information

BOXED 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.

For Seattle Genetics:

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 future clinical trials 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-K for the year ended December 31, 2011 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.

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Editor’s Note: This press release is also available under the Media section of the Company’s website at: www.millennium.com/InTheNews.aspx.