On November 25, 2019 Seattle Genetics, Inc. (Nasdaq:SGEN) reported that Health Canada has approved the supplemental New Drug Submission that expands the use of ADCETRIS (brentuximab vedotin) 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 tumours express CD30 (Press release, Seattle Genetics, NOV 25, 2019, View Source [SID1234551660]). The approval is based on positive results of the phase 3 ECHELON-2 clinical trial that compared ADCETRIS plus CHP to CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone). Health Canada granted a Priority Review Designation for this submission. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed on the surface of several types of PTCL.
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"The Health Canada approval of ADCETRIS (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, M.D., 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 ADCETRIS (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."
"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," said Roger Dansey, M.D., Chief Medical Officer at Seattle Genetics. "With this new indication for ADCETRIS, 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 ADCETRIS globally to patients in need."
In May 2019, Health Canada approved the supplemental New Drug Submission that expanded the use of ADCETRIS 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 3 ECHELON-1 clinical trial.
About T-Cell Lymphomas
There are more than 60 subtypes of non-Hodgkin lymphomas which are broadly divided into two major groups: B-cell lymphomas, which develop from abnormal B-lymphocytes, and T-cell lymphomas, which develop from abnormal T-lymphocytes. There are many different forms of T-cell lymphomas, some of which are extremely rare. T-cell lymphomas can be aggressive (fast-growing) or indolent (slow-growing). PTCL accounts for approximately 10 percent of non-Hodgkin lymphoma cases in the U.S. and Europe and may be as high as 24 percent in parts of Asia.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas. These include three completed phase 3 trials: ECHELON-2 trial in frontline peripheral T-cell lymphomas, ECHELON-1 in previously untreated Hodgkin lymphoma, and ALCANZA in cutaneous T-cell lymphoma.
ADCETRIS 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 tumor cells.
ADCETRIS injection for intravenous infusion has received FDA approval for six indications in adult patients with: (1) previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone, (2) previously untreated Stage III or IV classical Hodgkin lymphoma (cHL), in combination with doxorubicin, vinblastine, and dacarbazine, (3) cHL at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation, (4) cHL after failure of auto-HSCT or failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (5) sALCL after failure of at least one prior multi-agent chemotherapy regimen, and (6) primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy.
Health Canada granted ADCETRIS approval with conditions in 2013 for patients with (1) HL after failure of autologous stem cell transplant (ASCT) or after failure of at least two multi-agent chemotherapy regimens in patients who are not ASCT candidates and (2) sALCL after failure of at least one multi-agent chemotherapy regimen. Non-conditional approval was granted for (3) post-ASCT consolidation treatment of patients with HL at increased risk of relapse or progression in 2017, (4) adult patients with pcALCL or CD30-expressing MF who have received prior systemic therapy in 2018, (5) for previously untreated patients with Stage IV HL in combination with doxorubicin, vinblastine, and dacarbazine in 2019, and (6) for previously untreated adult patients with sALCL, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS) or angioimmunoblastic T-cell lymphoma (AITL), whose tumors express CD30, in combination with cyclophosphamide, doxorubicin, prednisone in 2019.
ADCETRIS received conditional marketing authorization from the European Commission in October 2012. The approved indications in Europe are: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following ASCT, or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, (2) for the treatment of adult patients with relapsed or refractory sALCL, (3) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy and (5) for the treatment of adult patients with previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with AVD (Adriamycin, vinblastine and dacarbazine).
ADCETRIS has received marketing authorization by regulatory authorities in 73 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See select important safety information, including Boxed Warning, below.
Seattle Genetics and Takeda are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and Takeda has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and Takeda are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where Takeda is solely responsible for development costs.