Health Canada, the federal department responsible for helping Canadians maintain and improve their health, has issued a non-conditional marketing authorization for use of brentuximab vedotin (Adcetris®; Seattle Genetics) as post-autologous stem cell transplant (ASCT) consolidation treatment of patients with Hodgkin lymphoma (HL) at increased risk of relapse or progression.
In 2013 Health Canada granted brentuximab vedotin approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
Brentuximab vedotin is an antibody-drug conjugate or 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-positive tumor cells.
The drug is used in the treatment of lymphoma, 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 expresses CD30.
Fig 1.0: The AETHERA Trial is a Phase III Study of brentuximab vedotin, also known as SGN-35, in Patients at High Risk of Residual Hodgkin Lymphoma Following Stem Cell Transplant. PFS follow-up (year 2) included continued monitoring with scans at 18 and 24 months and quarterly clinical assessments. Patients in this trial who experienced disease progression per investigator during the study were unblinded and could receive brentuximab vedotin as part of a separate trial.AETHERA trial
The newly approved indication is based on positive results from the phase III AETHERA clinical trial. [1] Brentuximab vedotin previously received approval with conditions in Canada for two lymphoma indications: HL patients who relapse after ASCT or relapse after at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates; and for systemic anaplastic large cell lymphoma (sALCL) patients who relapse after at least one multi-agent chemotherapy regimen.
“With this expanded brentuximab vedotin label, physicians and eligible patients in Canada will have further access to this important therapeutic option for treating Hodgkin lymphoma,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics.
“This is one of several brentuximab vedotin regulatory milestones during 2017 towards our goal of expanding its availabilty globally to patients in need. We recently submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) for brentuximab vedotin approval in cutaneous T-cell lymphoma based primarily on our phase III ALCANZA clinical trial, and we plan to submit a supplemental BLA to the FDA for brentuximab vedotin in frontline Hodgkin lymphoma based on the positive phase III ECHELON-1 clinical trial. We plan to follow up with submissions to Health Canada for indications in these settings,” Siegall added.
Brentuximab vedotin is currently not approved for use in Cutaneous T-Cell Lymphoma (CTCL) or frontline Hodgkin lymphoma.
