Seattle Genetics, Inc. and Millennium: The Takeda Oncology Company, a wholly owned subsidiary of Takeda Pharmaceutical Company Limited have completed patient enrollment in phase III clinical trial of Adcetris (brentuximab vedotin) for post-transplant Hodgkin lymphoma (HL) patients. The phase III trial, also known as the AETHERA trial, is evaluating Adcetris versus placebo for the treatment of patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant (ASCT).
Adcetris is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL.
“We are pleased to complete the enrollment of this important phase III trial, evaluating the use of Adcetris for Hodgkin lymphoma patients who are at high risk of residual disease following an ASCT,” said Thomas C Reynolds, MD, PhD, chief medical officer of Seattle Genetics. “The AETHERA trial is designed to provide the medical community with valuable insight into the potential for Adcetris to consolidate responses in Hodgkin lymphoma patients following a transplant, and will be the first data on the use of Adcetris in a maintenance-type setting. We anticipate data from this trial will be available in late 2013 or early 2014.”
“Completing enrollment of the AETHERA trial in the post-transplant Hodgkin lymphoma patient population at high risk for residual disease is a significant milestone for our Adcetris clinical development programme,” said Karen Ferrante, MD, chief medical officer, Millennium. “We look forward to continuing to work with our partner Seattle Genetics to determine the potential benefit of this targeted treatment in other CD30-expressing tumours.”
The AETHERA trial is a randomized, double-blind, placebo-controlled phase III study, comparing progression-free survival in 329 post-ASCT patients receiving AdcetrisAdcetris to those receiving placebo. Patients must be at high risk for residual HL, defined as those with a history of refractory HL, 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 receive Adcetris every three weeks for up to approximately one year. This international multi-center trial is being conducted in the United States, Europe and Russia.
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 tumour cells.
Adcetris received accelerated approval from the US Food and Drug Administration (FDA) for two indications: 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 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.
Adcetris is not approved for use outside the United States. The marketing authorization application for ADCETRIS in relapsed or refractory Hodgkin lymphoma and sALCL, filed by Takeda Global Research & Development Centre (Europe), 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 approval of Adcetris, supporting an approval decision in the European Union.
Seattle Genetics and Millennium are jointly developing Adcetris. Under the terms of the collaboration agreement, Seattle Genetics has US 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.
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.
Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer.
Millennium: The Takeda Oncology Company, a leading biopharmaceutical company was acquired by Takeda Pharmaceutical Company Ltd. The Company’s research, development and commercialization activities are focused in oncology.