On May 3, 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 AVD (Adriamycin, vinblastine and dacarbazine) chemotherapy in patients with previously untreated Stage IV Hodgkin lymphoma (HL) (Press release, Seattle Genetics, MAY 3, 2019, View Source [SID1234535704]). The approval is based on positive results of the phase 3 ECHELON-1 clinical trial that compared ADCETRIS plus AVD to ABVD (Adriamycin, bleomycin, vinblastine and dacarbazine). In addition, a supplemental New Drug Submission was recently submitted to Health Canada for ADCETRIS in combination with CHP (cyclophosphamide, doxorubicin, prednisone) in patients with previously untreated CD30-expressing peripheral T-cell lymphoma (PTCL) based on the positive phase 3 ECHELON-2 clinical trial results. Health Canada granted a Priority Review Designation for this submission. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical HL and expressed on the surface of several types of PTCL.
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"The Health Canada approval of ADCETRIS in combination with AVD chemotherapy in advanced-stage (Stage IV) Hodgkin lymphoma represents the first major advance for patients 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 both the phase 3 ECHELON-1 and ECHELON-2 clinical trials. "Advanced-stage Hodgkin lymphoma tends to be more aggressive and difficult to treat. This new ADCETRIS-containing regimen demonstrated superior efficacy when compared to the standard of care ABVD chemotherapy in the phase 3 ECHELON-1 clinical trial supporting the Health Canada approval and represents a meaningful advance for this Hodgkin lymphoma patient population."
"Currently, up to 30 percent of newly diagnosed patients with advanced-stage Hodgkin lymphoma will experience disease progression after treatment with the current standard of care, representing a significant need for improved treatment options," said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. "With this new indication for ADCETRIS, physicians and eligible patients in Canada have access to this important new regimen for treating Stage IV Hodgkin lymphoma. We also recently submitted a supplemental New Drug Submission application to Health Canada, which was granted Priority Review Designation, for ADCETRIS in combination with chemotherapy in frontline PTCL, a milestone supporting our plans to expand ADCETRIS globally to patients in need."
In March 2018, the U.S. Food and Drug Administration (FDA) approved ADCETRIS in combination with AVD for the treatment of adult patients with previously untreated stage III or IV classical HL based on the results of the phase 3 ECHELON-1 clinical trial. In November 2018, the FDA approved ADCETRIS in combination with CHP for the treatment of adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing PTCL, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
About Classical Hodgkin Lymphoma
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. Classical 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.
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. The ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin lymphoma is ongoing.
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 for relapsed or refractory Hodgkin lymphoma and sALCL in 2013, and non-conditional approval for post-autologous stem cell transplantation (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression in 2017, adults with pcALCL or CD30-expressing MF who have had prior systemic therapy in 2018, and for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine 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 72 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.