-ECHELON-2 Trial Represents Key Component of Late-Stage Clinical Development Strategy to Establish ADCETRIS as Foundation of Care for CD30-Expressing Lymphomas-

-Data from ECHELON-2 Phase 3 Trial Expected in 2017 to 2018 Timeframe-

BOTHELL, WA & CAMBRIDGE, MA, USA I November 8, 2016 I Seattle Genetics, Inc. (Nasdaq: SGEN) and Takeda Pharmaceutical Company Limited (TSE:4502) today announced completion of patient enrollment in the ECHELON-2 clinical trial. ECHELON-2 is a global phase 3 randomized trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in patients with previously untreated CD30-positive mature T-cell lymphoma (MTCL). ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on several types of non-Hodgkin lymphoma, including subsets of MTCL, as well as Hodgkin lymphoma. ADCETRIS is currently not approved for the frontline treatment of MTCL.

Patients in ECHELON-2 were randomized to receive a novel combination regimen consisting of ADCETRIS plus cyclophosphamide (C), doxorubicin (H) and prednisone (P) (referred to as A+CHP) versus cyclophosphamide, doxorubicin, vincristine (O) and prednisone (referred to as CHOP), the recognized standard of care treatment regimen for frontline MTCL. The trial enrolled 452 patients. The ECHELON-2 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 European Medicines Agency (EMA) scientific advice.

“Our goal is to establish ADCETRIS as the foundation of care for CD30-expressing lymphomas and redefine frontline treatment in Hodgkin lymphoma and MTCL through our broad, late-stage clinical development program currently underway. The ECHELON-2 clinical trial represents our fourth phase 3 study to complete enrollment,” said Naomi Hunder, M.D., Vice President, Clinical Development at Seattle Genetics. “We look forward to the results of the ECHELON-2 frontline MTCL study in the 2017 to 2018 timeframe and expect to refine the timeline in the future. The ultimate goal of this phase 3 trial is to improve outcomes for frontline patients with CD30-expressing MTCL and, if the trial results are positive, to submit data from this trial to regulatory agencies to expand the label for ADCETRIS use in the frontline setting.”

“Mature T-cell lymphoma is a rare, aggressive type of cancer in which the standard of care chemotherapy regimen has not changed in decades,” said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “Achieving target enrollment represents a key milestone for ECHELON-2 as we evaluate the efficacy and safety of brentuximab vedotin in newly diagnosed mature T-cell lymphoma patients, and to our ultimate goal of bringing important new therapies to patients with CD30-positive malignancies.”

Data from a phase 1 trial evaluating ADCETRIS plus CHP in MTCL were previously presented at the American Society of Hematology (ASH) Annual Meetings in 2012 and 2015. Data demonstrated that 26 of 26 patients (100 percent) achieved an objective response, including 23 (88 percent) with a complete remission and three patients (12 percent) with a partial remission. Long-term follow-up data estimated the three-year overall survival was 80 percent and three-year progression-free survival was 52 percent, with no patients receiving a consolidative stem cell transplant in first remission. Three-year overall survival and progression-free survival rates of less than 40 percent and 30 percent, respectively, have previously been reported for patients in this setting treated with CHOP (Reimer et al., J Clin Oncol 27: 106-113; 2009; Fanale et al., J Clin Oncol 32: 3137-3143; 2014).The most common adverse events of any grade occurring in more than 30 percent of patients in this phase 1 trial were peripheral sensory neuropathy, diarrhea, fatigue and hair loss. Additional four-year follow-up data from this trial will be presented in a poster presentation at the 2016 ASH Annual Meeting.

ECHELON-2 Trial Design

The double-blind, placebo-controlled global phase 3 trial is investigating ADCETRIS plus CHP versus CHOP as frontline therapy in patients with CD30-positive MTCL. The primary endpoint is progression-free survival per independent review facility assessment using the Cheson 2007 Revised Response Criteria for Malignant Lymphoma. Secondary endpoints include overall survival, complete remission rate and safety. The multi-center trial is being conducted in North America, Europe and Asia. The study enrolled 452 patients, with approximately 225 patients per treatment arm. Data from the trial will be available when a pre-specified number of progression-free survival events have occurred.

For more information about the trial, please visit www.clinicaltrials.gov.

About T-Cell Lymphomas

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. Non-Hodgkin lymphomas are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. The World Health Organization identifies 22 subtypes of mature T- and NK-cell neoplasms, including systemic anaplastic large cell lymphoma (ALCL) which is an aggressive type of T-cell non-Hodgkin lymphoma that expresses CD30. Other mature T-cell lymphomas include peripheral T-cell lymphoma (PTCL), angioimmunoblastic T-cell lymphoma and adult T-cell lymphoma.


ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including two phase 3 studies, ECHELON-1 in frontline classical Hodgkin lymphoma and ECHELON-2 in frontline mature T-cell lymphomas, as well as trials in many additional types of CD30-expressing malignancies, including B-cell lymphomas.

ADCETRIS 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 for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.

ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL. ADCETRIS has received marketing authorization by regulatory authorities in 65 countries.

In June 2016, the European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT. See important safety information below.

Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.

About Seattle Genetics

Seattle Genetics is an innovative biotechnology company that develops and commercializes novel antibody-based therapies for the treatment of cancer. The company’s industry-leading antibody-drug conjugate (ADC) technology harnesses the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. ADCETRIS® (brentuximab vedotin), the company’s lead product, in collaboration with Takeda Pharmaceutical Company Limited, is the first in a new class of ADCs commercially available globally in 65 countries for relapsed classical Hodgkin lymphoma and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing vadastuximab talirine (SGN-CD33A; 33A), an ADC in a phase 3 trial for acute myeloid leukemia. Headquartered in Bothell, Washington, Seattle Genetics has a robust pipeline of innovative therapies for blood-related cancers and solid tumors designed to address significant unmet medical needs and improve treatment outcomes for patients. The company has collaborations for its proprietary ADC technology with a number of companies including AbbVie, Astellas, Bayer, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.

About Takeda

Takeda Pharmaceutical Company Limited is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.

SOURCE: Seattle Genetics