Takeda, Millennium, Seattle Genetics Begin Brentuximab Vedotin Phase III Aethera Trial

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, is expected to evaluate Brentuximab vedotin versus placebo for the treatment of patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant (ASCT).

The Aethera trial is a randomised, double-blind, placebo-controlled Phase III study comparing progression-free survival in approximately 325 post-ASCT patients receiving Brentuximab vedotin to those receiving placebo.

Seattle Genetics is developing Brentuximab vedotin in collaboration with Millennium, under which Seattle Genetics has US and Canadian commercialisation rights and the Takeda Group has rights to commercialise 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.

Reportedly, as per 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 Centralised Scientific Advice from the EMA. The trial is designed to form the basis for registrational filings with the FDA and EMA under the accelerated approval and conditional authorization regulations.

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.

Thomas Reynolds, chief medical officer of Seattle Genetics, said: “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 FDA and European Medicines Agency (EMA) during the first half of 2011 under the accelerated approval and conditional authorization regulations respectively.

“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.”

Nancy Simonian, chief medical officer of Millennium, said: “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. The initiation of this Phase III trial is aimed to support the ongoing pivotal trial of Brentuximab vedotin.”