Health Canada, the Canadian regulatory counterpart of the U.S. Food and Drug Administration (FDA), has approved the supplemental New Drug Submission that expands the use of brentuximab vedotin (Adcetris®; Seattle Genetics/Takeda) in combination with CHP (cyclophosphamide, doxorubicin, prednisone) chemotherapy for the treatment of previously untreated adult patients with systemic anaplastic large cell lymphoma (sALCL), peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30.
The approval of brentuximab vedotin in this indication is based on positive results of the phase III ECHELON-2 clinical trial that compared brentuximab vedotin plus CHP to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone).
Health Canada granted a Priority Review Designation for this submission.
Brentuximab vedotin is an antibody-drug conjugate or ADC directed to CD30, which is expressed on the surface of several types of peripheral T-cell lymphoma (PTCL). The drug’s anti-CD30 monoclonal antibody is attached by a protease-cleavable linker to a microtubule disrupting agent, monomethyl auristatin E (MMAE).
ADCs are highly targeted biopharmaceutical drugs that combine monoclonal antibodies specific to surface antigens present on particular tumor cells with highly potent anti-cancer agents linked via a chemical linker.
With five approved drugs on the market, these novel, targeted drugs have become a powerful class of therapeutic agents in oncology and hematology.
“The Health Canada approval of brentuximab vedotin in combination with CHP chemotherapy in newly diagnosed CD30-expressing peripheral T-cell lymphoma represents the first major advance for Canadian patients with PTCL in decades,” said Kerry Savage, MD., Medical Oncologist at the BC Cancer Agency, Professor of Medicine at the University of British Columbia and investigator on the ECHELON-2 clinical trial.
“The approval is based on the ECHELON-2 clinical trial that demonstrated brentuximab vedotin plus CHP regimen was superior for both progression-free survival and all key secondary endpoints, including overall survival, when compared to the standard of care CHOP chemotherapy,” Savage added.
Standard of Care
“The current standard of care for initial treatment of peripheral T-cell lymphoma is multi-agent chemotherapy, which results in low complete remission rates and poor progression-free and overall survival. ECHELON-2 is the first randomized trial to demonstrate an overall survival benefit over established standard therapy, making it a meaningful advance in the treatment of these rare lymphomas,” noted Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics.
“With this new indication for brentuximab vedotin, physicians and eligible patients in Canada now have access to this important new regimen for treating frontline CD30-expressing peripheral T-cell lymphoma, another milestone supporting our plans to continue to expand brentuximab vedotin globally to patients in need.”
Approval in Hodgkin lymphoma
In May 2019, Health Canada approved the supplemental New Drug Submission that expanded the use of brentuximab vedotin in combination with AVD (Adriamycin, vinblastine and dacarbazine) chemotherapy in patients with previously untreated Stage IV Hodgkin lymphoma (HL) based on the results of the phase III ECHELON-1 clinical trial.
Brentuximab vedotin has received marketing authorization by regulatory authorities in 73 countries for relapsed or refractory Hodgkin lymphoma and systemic anaplastic large cell lymphomas (ALCL).
ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas (ECHELON-2) – NCT01777152