– Opinion Based on Phase 3 ECHELON-2 Study Which Demonstrated ADCETRIS Plus Chemotherapy Resulted in a Statistically Significant Improvement in Progression-Free Survival Compared to a Standard of Care
CAMBRIDGE, MA, USA and OSSAKA, JAPAN I March 31, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the extension of the marketing authorization of ADCETRIS® (brentuximab vedotin) and recommended its approval in combination with CHP (cyclophosphamide, doxorubicin, prednisone) as a treatment for adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL). The positive CHMP opinion is based on the results of the Phase 3 ECHELON-2 study evaluating ADCETRIS in combination with CHP to a standard care, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated patients with CD30+ peripheral T-cell lymphoma (PTCL), including the subtype sALCL. ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, which is expressed on the surface of several types of PTCL, including sALCL.
“There have been no significant treatment advancements for PTCL over the last few decades. Historically there have been a lack of randomized clinical studies in this setting, making it a challenge to establish an optimal therapy for these patients,” said Eva Domingo-Domenech, MD, Institut Català d’Oncologia – Hospitalet, Hospital Duran i Reynals. “Outcomes with currently available therapies are often poor, and there is an urgent need for new treatment options. If approved for adult patients with previously untreated sALCL, ADCETRIS may offer an important option for European patients.”
“The positive CHMP opinion marks an important step forward for the European sALCL community,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “ECHELON-2 showed that ADCETRIS plus CHP demonstrated a significant improvement in progression-free survival and overall survival while maintaining a safety profile comparable to the standard of care of CHOP. We look forward to the European Commission’s review of this positive opinion and hope to bring ADCETRIS to eligible patients in need.”
The opinion for ADCETRIS will now be reviewed by the European Commission (EC) for Commission Decision. ADCETRIS is currently not approved as a therapy for frontline sALCL in Europe.
The ECHELON-2 study met its primary endpoint with ADCETRIS plus CHP demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by an Independent Review Committee (hazard ratio [HR]=0.71; p-value=0.0110), 29 percent improvement in PFS. The safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy.
About the ECHELON-2 Trial
ECHELON-2 is a randomized, double-blind, placebo-controlled Phase 3 trial and is investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The primary endpoint is progression-free survival (PFS) per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease. Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety. The multi-center trial was conducted at sites across North America, Europe and Asia and enrolled 452 patients. The majority of patient enrolled had sALCL.
About T-Cell Lymphomas
There are more than 100 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 an antibody-drug conjugate (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.
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, for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019 and 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 previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) 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, (4) for the treatment of adult patients with relapsed or refractory sALCL and (5) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
In Japan, ADCETRIS received its first approval in January 2014 for relapsed or refractory Hodgkin lymphoma and ALCL, and untreated Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in September 2018, and Peripheral T-cell lymphomas in December 2019. In December 2019, ADCETRIS obtained additional dosage & administration for the treatment of relapsed or refractory Hodgkin lymphoma and Peripheral T-cell lymphomas in pediatric. The current wording of approved indication in Japan package insert is for the treatment of patients with CD30 positive: Hodgkin lymphoma and Peripheral T-cell lymphomas.
ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries/ regions for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.
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.
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.
For more information, visit https://www.takeda.com.
Takeda’s Commitment to Oncology
Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.
SOURCE: Takeda Pharmaceutical Co
Post Views: 64
– Opinion Based on Phase 3 ECHELON-2 Study Which Demonstrated ADCETRIS Plus Chemotherapy Resulted in a Statistically Significant Improvement in Progression-Free Survival Compared to a Standard of Care
CAMBRIDGE, MA, USA and OSSAKA, JAPAN I March 31, 2020 I Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) (“Takeda”) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) granted a positive opinion for the extension of the marketing authorization of ADCETRIS® (brentuximab vedotin) and recommended its approval in combination with CHP (cyclophosphamide, doxorubicin, prednisone) as a treatment for adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL). The positive CHMP opinion is based on the results of the Phase 3 ECHELON-2 study evaluating ADCETRIS in combination with CHP to a standard care, CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), in previously untreated patients with CD30+ peripheral T-cell lymphoma (PTCL), including the subtype sALCL. ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, which is expressed on the surface of several types of PTCL, including sALCL.
“There have been no significant treatment advancements for PTCL over the last few decades. Historically there have been a lack of randomized clinical studies in this setting, making it a challenge to establish an optimal therapy for these patients,” said Eva Domingo-Domenech, MD, Institut Català d’Oncologia – Hospitalet, Hospital Duran i Reynals. “Outcomes with currently available therapies are often poor, and there is an urgent need for new treatment options. If approved for adult patients with previously untreated sALCL, ADCETRIS may offer an important option for European patients.”
“The positive CHMP opinion marks an important step forward for the European sALCL community,” said Christopher Arendt, Head, Oncology Therapeutic Area Unit, Takeda. “ECHELON-2 showed that ADCETRIS plus CHP demonstrated a significant improvement in progression-free survival and overall survival while maintaining a safety profile comparable to the standard of care of CHOP. We look forward to the European Commission’s review of this positive opinion and hope to bring ADCETRIS to eligible patients in need.”
The opinion for ADCETRIS will now be reviewed by the European Commission (EC) for Commission Decision. ADCETRIS is currently not approved as a therapy for frontline sALCL in Europe.
The ECHELON-2 study met its primary endpoint with ADCETRIS plus CHP demonstrating a statistically significant improvement in progression-free survival (PFS) as assessed by an Independent Review Committee (hazard ratio [HR]=0.71; p-value=0.0110), 29 percent improvement in PFS. The safety profile of ADCETRIS plus CHP in the ECHELON-2 trial was comparable to CHOP and consistent with the established safety profile of ADCETRIS in combination with chemotherapy.
About the ECHELON-2 Trial
ECHELON-2 is a randomized, double-blind, placebo-controlled Phase 3 trial and is investigating ADCETRIS plus CHP (cyclophosphamide, doxorubicin, prednisone) versus CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) as frontline therapy in patients with CD30-expressing peripheral T-cell lymphoma, also known as mature T-cell lymphoma. The primary endpoint is progression-free survival (PFS) per Independent Review Facility assessment, with events defined as progression, death, or receipt of chemotherapy for residual or progressive disease. Secondary endpoints include PFS in patients with systemic anaplastic large cell lymphoma (sALCL), complete remission rate, overall survival and objective response rate, in addition to safety. The multi-center trial was conducted at sites across North America, Europe and Asia and enrolled 452 patients. The majority of patient enrolled had sALCL.
About T-Cell Lymphomas
There are more than 100 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 an antibody-drug conjugate (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.
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, for previously untreated Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in 2019 and 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 previously untreated CD30-positive Stage IV Hodgkin lymphoma in combination with doxorubicin, vinblastine and dacarbazine (AVD), (2) for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT, (3) 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, (4) for the treatment of adult patients with relapsed or refractory sALCL and (5) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
In Japan, ADCETRIS received its first approval in January 2014 for relapsed or refractory Hodgkin lymphoma and ALCL, and untreated Hodgkin lymphoma in combination with doxorubicin, vinblastine, and dacarbazine in September 2018, and Peripheral T-cell lymphomas in December 2019. In December 2019, ADCETRIS obtained additional dosage & administration for the treatment of relapsed or refractory Hodgkin lymphoma and Peripheral T-cell lymphomas in pediatric. The current wording of approved indication in Japan package insert is for the treatment of patients with CD30 positive: Hodgkin lymphoma and Peripheral T-cell lymphomas.
ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries/ regions for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information below.
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including a Phase 3 study in first-line Hodgkin lymphoma (ECHELON-1) and another Phase 3 study in first-line CD30-positive peripheral T-cell lymphomas (ECHELON-2), as well as trials in many additional types of CD30-positive malignancies.
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.
About Takeda Pharmaceutical Company
Takeda Pharmaceutical Company Limited (TSE:4502/NYSE:TAK) is a global, values-based, R&D-driven biopharmaceutical leader headquartered in Japan, committed to bringing Better Health and a Brighter Future to patients by translating science into highly-innovative medicines. Takeda focuses its R&D efforts on four therapeutic areas: Oncology, Rare Diseases, Neuroscience, and Gastroenterology (GI). We also make targeted R&D investments in Plasma-Derived Therapies and Vaccines. We are focusing on developing highly innovative medicines that contribute to making a difference in people’s lives by advancing the frontier of new treatment options and leveraging our enhanced collaborative R&D engine and capabilities to create a robust, modality-diverse pipeline. Our employees are committed to improving quality of life for patients and to working with our partners in health care in approximately 80 countries.
For more information, visit https://www.takeda.com.
Takeda’s Commitment to Oncology
Our core R&D mission is to deliver novel medicines to patients with cancer worldwide through our commitment to science, breakthrough innovation and passion for improving the lives of patients. Whether it’s with our hematology therapies, our robust pipeline, or solid tumor medicines, we aim to stay both innovative and competitive to bring patients the treatments they need. For more information, visit www.takedaoncology.com.
SOURCE: Takeda Pharmaceutical Co
Post Views: 64
