Phase III trial of brentuximab vedotin for post-transplant Hodgkin lymphoma initiated

Seattle Genetics, Inc. (NASDAQ:SGEN), Takeda Pharmaceutical Company Limited (TOKYO:4502) and its wholly owned subsidiary Millennium: The Takeda Oncology Company today announced the initiation of a phase III clinical trial of brentuximab vedotin (SGN-35) for post-transplant Hodgkin lymphoma patients. Brentuximab vedotin is an antibody-drug conjugate (ADC) targeted to CD30, which is expressed on malignant Hodgkin lymphoma cells. The phase III trial, also known as AETHERA, will evaluate brentuximab vedotin versus placebo for the treatment of patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant (ASCT).

“The initiation of this phase III trial is aimed to support the ongoing pivotal trial of brentuximab vedotin and further enables the Takeda Group to move toward its goal of global oncology leadership.”

"Our initial approval strategy for brentuximab vedotin is based on our ongoing pivotal trial in relapsed and refractory Hodgkin lymphoma, from which data are expected in the second half of 2010. The pivotal trial is designed to form the basis for registrational filings with the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) during the first half of 2011 under the accelerated approval and conditional authorization regulations respectively," said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. "The AETHERA trial is part of our broader development strategy and is designed to fulfill regulatory requirements for full approval in the United States and Europe. In addition, this trial will provide data on the use of brentuximab vedotin earlier in Hodgkin lymphoma therapy as part of an integrated second-line regimen with ASCT."

"Brentuximab vedotin has the potential to address a large unmet medical need in the patient community. By utilizing Seattle Genetics' ADC technology, the molecule selectively targets CD30, potentially making it the first new drug in more than a decade for patients with relapsed Hodgkin lymphoma," said Nancy Simonian, M.D., Chief Medical Officer of Millennium. "The initiation of this phase III trial is aimed to support the ongoing pivotal trial of brentuximab vedotin and further enables the Takeda Group to move toward its goal of global oncology leadership."

The AETHERA trial is a randomized, double-blind, placebo-controlled phase III study comparing progression-free survival in approximately 325 post-ASCT patients receiving brentuximab vedotin to those receiving placebo. Patients must be at high risk for residual Hodgkin lymphoma, defined as those with a history of refractory Hodgkin lymphoma, those who relapse or progress within one year from receiving front-line chemotherapy and/or those who have disease outside of the lymph nodes at the time of pre-ASCT relapse. Secondary endpoints of the trial include overall survival, safety and tolerability. Patients will receive brentuximab vedotin every three weeks for up to approximately one year. This international multi-center trial will be conducted in the United States, Europe and Russia.

Seattle Genetics is developing brentuximab vedotin in collaboration with Millennium, under which Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize brentuximab vedotin in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for brentuximab vedotin on a 50:50 basis, except in Japan where the Takeda Group will be solely responsible for development costs.

Under the collaboration, Seattle Genetics and Millennium are conducting a pivotal trial of brentuximab vedotin for relapsed and refractory Hodgkin lymphoma under a Special Protocol Assessment (SPA) with the FDA, and top-line data are expected in the second half of 2010. The pivotal trial also received EU Centralized Scientific Advice from the EMA. The pivotal trial is designed to form the basis for registrational filings with the FDA and EMA under the accelerated approval and conditional authorization regulations. These regulations provide a mechanism for making promising products for life-threatening diseases commercially available on the basis of preliminary evidence prior to formal demonstration of patient benefit.

In addition, the companies are conducting a phase II trial for relapsed and refractory systemic anaplastic large cell lymphoma, a phase II retreatment trial for relapsed patients who previously responded to brentuximab vedotin therapy, and a phase I combination trial for front-line Hodgkin lymphoma.