– If Authorized in Europe, ADCETRIS in Combination with AVD (Adriamycin, Vinblastine and Dacarbazine) Will Be the First New Treatment Regimen Available for Adult Patients with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma in Decades –
– Opinion Based on Positive Phase 3 ECHELON-1 Study Results, Which Demonstrated ADCETRIS Combination Improved Outcomes and Reduced the Need for Additional Treatment in Adult Patients Versus ABVD (Adriamycin, Bleomycin, Vinblastine and Dacarbazine), a Current Standard of Care –
CAMBRIDGE, MA, USA & OSAKA, Japan I December 14, 2018 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the extension of the marketing authorization of ADCETRIS (brentuximab vedotin) and recommended its approval in combination with AVD in adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma. ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma. ADCETRIS is currently not approved as a therapy for previously untreated Hodgkin lymphoma in Europe.
“For a large number of previously untreated Hodgkin lymphoma patients diagnosed with Stage IV disease, progression will occur with current treatments, highlighting a true unmet need in this population,” said Anna Sureda, M.D., Ph.D., Head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d’Oncologia – Hospital Duran i Reynals. “In the ECHELON-1 clinical trial, ADCETRIS in combination with AVD reduced the risk of progression, death or need for subsequent anticancer therapy in patients with Stage IV disease by 29 percent versus ABVD, a standard of care. If approved in this indication, ADCETRIS may offer an important novel treatment option for previously untreated patients with Stage IV Hodgkin lymphoma in Europe.”
“Today’s positive CHMP opinion represents a significant step forward for the European Hodgkin lymphoma community,” said Jesús Gómez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “The results of the ECHELON-1 trial demonstrated a statistically significant improvement in modified progression-free survival of in patients who received ADCETRIS in combination with AVD compared to the control arm. In addition to demonstrating a safety profile that was generally consistent with that known for the single-agent components of the regimen, in the ADCETRIS containing arm, 35 percent fewer patients with Stage IV disease received subsequent salvage chemotherapy or high-dose chemotherapy and transplant. We look forward to the European Commission’s review of this CHMP positive opinion and hope to offer ADCETRIS as a treatment option to appropriate European Hodgkin lymphoma patients in the future.”
The submission for ADCETRIS will now be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the 28-member states of the European Union (EU). Decisions by the EC are also applicable in Norway, Liechtenstein and Iceland.
The positive CHMP opinion is based on the results of the Phase 3 ECHELON-1 study designed to compare ADCETRIS plus AVD to ABVD as a therapy in adult patients with previously untreated Hodgkin lymphoma. The trial achieved its primary endpoint resulting in a statistically significant improvement in modified progression-free survival (PFS) versus the control arm (HR 0.77; p-value=0.035). Key subgroup analyses, such as modified PFS by disease stage, showed a larger effect in patients with Stage IV Hodgkin lymphoma in the ADCETRIS plus AVD arm versus the control arm (HR 0.71; p-value = 0.023). This corresponds to a 29 percent reduction in the risk of progression, death or need for additional anticancer therapy for Stage IV patients.
About the ECHELON-1 Trial
The randomized, open-label, two-arm, multi-center Phase 3 ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS+AVD resulting in a statistically significant improvement in modified progression-free survival (PFS) versus the control arm of ABVD as assessed by an Independent Review Facility (IRF) (HR 0.77; p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death or need for additional anticancer therapy.
- All secondary endpoints trended in favor of the ADCETRIS+AVD arm, including interim analysis of overall survival (OS; HR 0.72; p-value=0.19).
- In the ADCETRIS+AVD arm, 33 percent fewer patients received subsequent salvage chemotherapy or high-dose chemotherapy and transplant.
- The safety profile of ADCETRIS+AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen.
- The most common clinically relevant adverse events of any grade that occurred in at least 15 percent of patients in the ADCETRIS+AVD and ABVD arms were: neutropenia, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhea, pyrexia, peripheral neuropathy, abdominal pain and stomatitis. In both the ADCETRIS+AVD and ABVD arms, the most common Grade 3 or 4 events were neutropenia, febrile neutropenia and neutrophil count decrease.
About 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. 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.
According to the Lymphoma Coalition, approximately 67,000 people worldwide are diagnosed with Hodgkin lymphoma each year and more than 25,000 people die each year from this cancer.
Up to 30 percent of previously untreated Hodgkin lymphoma patients progress following their first therapy depending on the stage of the disease. Only 50 percent of patients with relapsed or refractory Hodgkin lymphoma achieve long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT), a historically used treatment regimen, highlighting the need for successful treatments for previously untreated patients.
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 transplant (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
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) 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, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries 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) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Approximately 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries.
For more information, visit https://www.takeda.com/newsroom/.
Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.
SOURCE: Takeda Pharmaceutical Co
Post Views: 679
– If Authorized in Europe, ADCETRIS in Combination with AVD (Adriamycin, Vinblastine and Dacarbazine) Will Be the First New Treatment Regimen Available for Adult Patients with Previously Untreated CD30+ Stage IV Hodgkin Lymphoma in Decades –
– Opinion Based on Positive Phase 3 ECHELON-1 Study Results, Which Demonstrated ADCETRIS Combination Improved Outcomes and Reduced the Need for Additional Treatment in Adult Patients Versus ABVD (Adriamycin, Bleomycin, Vinblastine and Dacarbazine), a Current Standard of Care –
CAMBRIDGE, MA, USA & OSAKA, Japan I December 14, 2018 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the European Medicines Agency’s (EMA) Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion for the extension of the marketing authorization of ADCETRIS (brentuximab vedotin) and recommended its approval in combination with AVD in adult patients with previously untreated CD30+ Stage IV Hodgkin lymphoma. ADCETRIS is an antibody-drug conjugate (ADC) directed at CD30, a defining marker of Hodgkin lymphoma. ADCETRIS is currently not approved as a therapy for previously untreated Hodgkin lymphoma in Europe.
“For a large number of previously untreated Hodgkin lymphoma patients diagnosed with Stage IV disease, progression will occur with current treatments, highlighting a true unmet need in this population,” said Anna Sureda, M.D., Ph.D., Head of the Hematology Department and Hematopoietic Stem Cell Transplant Programme, Institut Català d’Oncologia – Hospital Duran i Reynals. “In the ECHELON-1 clinical trial, ADCETRIS in combination with AVD reduced the risk of progression, death or need for subsequent anticancer therapy in patients with Stage IV disease by 29 percent versus ABVD, a standard of care. If approved in this indication, ADCETRIS may offer an important novel treatment option for previously untreated patients with Stage IV Hodgkin lymphoma in Europe.”
“Today’s positive CHMP opinion represents a significant step forward for the European Hodgkin lymphoma community,” said Jesús Gómez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “The results of the ECHELON-1 trial demonstrated a statistically significant improvement in modified progression-free survival of in patients who received ADCETRIS in combination with AVD compared to the control arm. In addition to demonstrating a safety profile that was generally consistent with that known for the single-agent components of the regimen, in the ADCETRIS containing arm, 35 percent fewer patients with Stage IV disease received subsequent salvage chemotherapy or high-dose chemotherapy and transplant. We look forward to the European Commission’s review of this CHMP positive opinion and hope to offer ADCETRIS as a treatment option to appropriate European Hodgkin lymphoma patients in the future.”
The submission for ADCETRIS will now be reviewed by the European Commission (EC), which has the authority to approve medicines for use in the 28-member states of the European Union (EU). Decisions by the EC are also applicable in Norway, Liechtenstein and Iceland.
The positive CHMP opinion is based on the results of the Phase 3 ECHELON-1 study designed to compare ADCETRIS plus AVD to ABVD as a therapy in adult patients with previously untreated Hodgkin lymphoma. The trial achieved its primary endpoint resulting in a statistically significant improvement in modified progression-free survival (PFS) versus the control arm (HR 0.77; p-value=0.035). Key subgroup analyses, such as modified PFS by disease stage, showed a larger effect in patients with Stage IV Hodgkin lymphoma in the ADCETRIS plus AVD arm versus the control arm (HR 0.71; p-value = 0.023). This corresponds to a 29 percent reduction in the risk of progression, death or need for additional anticancer therapy for Stage IV patients.
About the ECHELON-1 Trial
The randomized, open-label, two-arm, multi-center Phase 3 ECHELON-1 trial achieved its primary endpoint with the combination of ADCETRIS+AVD resulting in a statistically significant improvement in modified progression-free survival (PFS) versus the control arm of ABVD as assessed by an Independent Review Facility (IRF) (HR 0.77; p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death or need for additional anticancer therapy.
- All secondary endpoints trended in favor of the ADCETRIS+AVD arm, including interim analysis of overall survival (OS; HR 0.72; p-value=0.19).
- In the ADCETRIS+AVD arm, 33 percent fewer patients received subsequent salvage chemotherapy or high-dose chemotherapy and transplant.
- The safety profile of ADCETRIS+AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen.
- The most common clinically relevant adverse events of any grade that occurred in at least 15 percent of patients in the ADCETRIS+AVD and ABVD arms were: neutropenia, constipation, vomiting, fatigue, peripheral sensory neuropathy, diarrhea, pyrexia, peripheral neuropathy, abdominal pain and stomatitis. In both the ADCETRIS+AVD and ABVD arms, the most common Grade 3 or 4 events were neutropenia, febrile neutropenia and neutrophil count decrease.
About 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. 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.
According to the Lymphoma Coalition, approximately 67,000 people worldwide are diagnosed with Hodgkin lymphoma each year and more than 25,000 people die each year from this cancer.
Up to 30 percent of previously untreated Hodgkin lymphoma patients progress following their first therapy depending on the stage of the disease. Only 50 percent of patients with relapsed or refractory Hodgkin lymphoma achieve long-term remission with high-dose chemotherapy and an autologous stem cell transplant (ASCT), a historically used treatment regimen, highlighting the need for successful treatments for previously untreated patients.
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 transplant (ASCT) consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
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) 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, and (4) for the treatment of adult patients with CD30-positive cutaneous T-cell lymphoma (CTCL) after at least one prior systemic therapy.
ADCETRIS has received marketing authorization by regulatory authorities in more than 70 countries 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) is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and neuroscience therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. Innovative products, especially in oncology and gastroenterology, as well as Takeda’s presence in emerging markets, are currently fueling the growth of Takeda. Approximately 30,000 Takeda employees are committed to improving quality of life for patients, working with Takeda’s partners in health care in more than 70 countries.
For more information, visit https://www.takeda.com/newsroom/.
Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.
SOURCE: Takeda Pharmaceutical Co
Post Views: 679
