– Randomized Phase 3 Clinical Trial with ADCETRIS Met Primary Endpoint, Demonstrating a Statistically Significant Improvement in Modified Progression-Free Survival
-Abstract to be Submitted for Presentation at the 2017 ASH Annual Meeting; Regulatory Submissions Planned
-Seattle Genetics to Host Conference Call and Webcast Today at 8:30 a.m. ET
CAMBRIDGE, MA, USA, OSAKA, Japan and BOTHELL, WA, USA I June 26, 2017 I Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (NASDAQ: SGEN) today announced that the Phase 3 ECHELON-1 clinical trial met its primary endpoint of a statistically significant improvement in modified progression-free survival (PFS) versus the control arm. ECHELON-1 is a randomized, multicenter trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in 1,334 patients with previously untreated advanced classical Hodgkin lymphoma. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma. ADCETRIS is currently not approved as a frontline therapy for Hodgkin lymphoma.
Patients in ECHELON-1 were randomized to receive either a combination of ADCETRIS+AVD (Adriamycin, vinblastine, dacarbazine) or ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), a recognized standard of care for frontline Hodgkin lymphoma. The results of the ECHELON-1 trial demonstrated that combination treatment with ADCETRIS resulted in a statistically significant improvement in modified PFS versus the control arm as assessed by an Independent Review Facility (hazard ratio=0.770; p-value=0.035). The two-year modified PFS rate for patients in the ADCETRIS arm was 82.1 percent compared to 77.2 percent in the control arm. Interim analysis of overall survival (OS), the key secondary endpoint, also trended in favor of the ADCETRIS+AVD arm. An abstract will be submitted for data presentation at the American Society of Hematology (ASH) annual meeting, December 9-12, 2017, in Atlanta, Ga.
The safety profile of ADCETRIS+AVD in the ECHELON-1 trial was consistent with that known for the single-agent components of the regimen. There was an increased incidence of febrile neutropenia and peripheral neuropathy in the ADCETRIS+AVD arm. Febrile neutropenia was reduced through the use of prophylactic growth factors in a subset of patients, and peripheral neuropathy was managed through dose modifications. The control arm had an increased rate and severity of pulmonary toxicity.
“We are excited about the positive result which shows a statistically significant improvement in the primary endpoint of modified PFS,” said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “The results of this trial signify an important step forward in the development of ADCETRIS and have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
“The outcome of the Phase 3 ECHELON-1 trial represents a significant milestone for the Hodgkin lymphoma community,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “Seattle Genetics’ goal is to establish ADCETRIS as the foundation of care for CD30-expressing lymphomas, including Hodgkin lymphoma. Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin.”
Takeda and Seattle Genetics plan to submit these results to regulatory authorities for approval in their respective territories.
ECHELON-1 Phase 3 Clinical Trial Design
The randomized, open-label, Phase 3 trial is investigating ADCETRIS+AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma. The primary endpoint is modified progression-free survival per Independent Review Facility assessment using the Revised Response Criteria for Malignant Lymphoma. Modified PFS is defined as the time to progression, death or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy per Independent Review Facility. This endpoint was chosen as it provides a clearer picture of the efficacy of frontline chemotherapy and eliminates the confounding impact of salvage and consolidation chemotherapies and radiotherapy. Secondary endpoints include overall survival, complete remission and safety. The multi-center trial was conducted in North America, Europe, South America, Australia, Asia and Africa. The study enrolled 1,334 patients who had a histologically-confirmed diagnosis of Stage III or IV classical Hodgkin lymphoma and had not been previously treated with systemic chemotherapy or radiotherapy. The ECHELON-1 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.
Please see Important Safety Information at the end of this press release.
Seattle Genetics Conference Call Details
Seattle Genetics’ management will host a conference call and webcast to discuss this announcement. The event will be held today at 5:30 a.m. Pacific Time (PT) / 8:30 a.m. Eastern Time (ET). The live event will be available from Seattle Genetics’ website at http://www.seattlegenetics.com, under the Investors section, or by calling 877-723-9521 (domestic) or 719-325-2138 (international). The access code is 9916080. A replay of the discussion will be available beginning at approximately 8:30 a.m. PT / 11:30 a.m. ET today from Seattle Genetics’ website or by calling 888-203-1112 (domestic) or 719-457-0820 (international), using access code 9916080. The telephone replay will be available until 5:00 p.m. PT / 8:00 p.m. ET Wednesday, June 28, 2017.
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 ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas, including three Phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma, the completed ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas.
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 for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL.
In June 2016, the European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.
ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information 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.
About Takeda
Takeda Pharmaceutical Company Limited 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 central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.
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.
About Seattle Genetics
Seattle Genetics is an innovative biotechnology company that develops and commercializes novel antibody-based therapies for the treatment of cancer. The company’s industry-leading antibody-drug conjugate (ADC) technology harnesses the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. ADCETRIS® (brentuximab vedotin), the company’s lead product, in collaboration with Takeda Pharmaceutical Company Limited, is the first in a new class of ADCs commercially available globally in 67 countries for relapsed classical Hodgkin lymphoma and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing enfortumab vedotin, an ADC for metastatic urothelial cancer, in a planned pivotal trial in collaboration with Astellas. Headquartered in Bothell, Washington, Seattle Genetics has a robust pipeline of innovative therapies for blood-related cancers and solid tumors designed to address significant unmet medical needs and improve treatment outcomes for patients. The company has collaborations for its proprietary ADC technology with a number of companies including AbbVie, Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com
SOURCE: Takeda Pharmaceutical Co
Post Views: 46
– Randomized Phase 3 Clinical Trial with ADCETRIS Met Primary Endpoint, Demonstrating a Statistically Significant Improvement in Modified Progression-Free Survival
-Abstract to be Submitted for Presentation at the 2017 ASH Annual Meeting; Regulatory Submissions Planned
-Seattle Genetics to Host Conference Call and Webcast Today at 8:30 a.m. ET
CAMBRIDGE, MA, USA, OSAKA, Japan and BOTHELL, WA, USA I June 26, 2017 I Takeda Pharmaceutical Company Limited (TSE:4502) and Seattle Genetics, Inc. (NASDAQ: SGEN) today announced that the Phase 3 ECHELON-1 clinical trial met its primary endpoint of a statistically significant improvement in modified progression-free survival (PFS) versus the control arm. ECHELON-1 is a randomized, multicenter trial evaluating ADCETRIS (brentuximab vedotin) as part of a frontline combination chemotherapy regimen in 1,334 patients with previously untreated advanced classical Hodgkin lymphoma. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma. ADCETRIS is currently not approved as a frontline therapy for Hodgkin lymphoma.
Patients in ECHELON-1 were randomized to receive either a combination of ADCETRIS+AVD (Adriamycin, vinblastine, dacarbazine) or ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine), a recognized standard of care for frontline Hodgkin lymphoma. The results of the ECHELON-1 trial demonstrated that combination treatment with ADCETRIS resulted in a statistically significant improvement in modified PFS versus the control arm as assessed by an Independent Review Facility (hazard ratio=0.770; p-value=0.035). The two-year modified PFS rate for patients in the ADCETRIS arm was 82.1 percent compared to 77.2 percent in the control arm. Interim analysis of overall survival (OS), the key secondary endpoint, also trended in favor of the ADCETRIS+AVD arm. An abstract will be submitted for data presentation at the American Society of Hematology (ASH) annual meeting, December 9-12, 2017, in Atlanta, Ga.
The safety profile of ADCETRIS+AVD in the ECHELON-1 trial was consistent with that known for the single-agent components of the regimen. There was an increased incidence of febrile neutropenia and peripheral neuropathy in the ADCETRIS+AVD arm. Febrile neutropenia was reduced through the use of prophylactic growth factors in a subset of patients, and peripheral neuropathy was managed through dose modifications. The control arm had an increased rate and severity of pulmonary toxicity.
“We are excited about the positive result which shows a statistically significant improvement in the primary endpoint of modified PFS,” said Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, Takeda Pharmaceutical Company. “The results of this trial signify an important step forward in the development of ADCETRIS and have the potential to change the treatment approach of frontline advanced Hodgkin lymphoma.”
“The outcome of the Phase 3 ECHELON-1 trial represents a significant milestone for the Hodgkin lymphoma community,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “Seattle Genetics’ goal is to establish ADCETRIS as the foundation of care for CD30-expressing lymphomas, including Hodgkin lymphoma. Notably, this is the first clinical trial in frontline advanced Hodgkin lymphoma to show superior efficacy of a regimen that eliminates bleomycin.”
Takeda and Seattle Genetics plan to submit these results to regulatory authorities for approval in their respective territories.
ECHELON-1 Phase 3 Clinical Trial Design
The randomized, open-label, Phase 3 trial is investigating ADCETRIS+AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma. The primary endpoint is modified progression-free survival per Independent Review Facility assessment using the Revised Response Criteria for Malignant Lymphoma. Modified PFS is defined as the time to progression, death or receipt of additional anticancer therapy for patients who are not in complete response after completion of frontline therapy per Independent Review Facility. This endpoint was chosen as it provides a clearer picture of the efficacy of frontline chemotherapy and eliminates the confounding impact of salvage and consolidation chemotherapies and radiotherapy. Secondary endpoints include overall survival, complete remission and safety. The multi-center trial was conducted in North America, Europe, South America, Australia, Asia and Africa. The study enrolled 1,334 patients who had a histologically-confirmed diagnosis of Stage III or IV classical Hodgkin lymphoma and had not been previously treated with systemic chemotherapy or radiotherapy. The ECHELON-1 trial is being conducted under a Special Protocol Assessment (SPA) agreement from the U.S. Food and Drug Administration (FDA) and the trial also received European Medicines Agency (EMA) scientific advice.
Please see Important Safety Information at the end of this press release.
Seattle Genetics Conference Call Details
Seattle Genetics’ management will host a conference call and webcast to discuss this announcement. The event will be held today at 5:30 a.m. Pacific Time (PT) / 8:30 a.m. Eastern Time (ET). The live event will be available from Seattle Genetics’ website at http://www.seattlegenetics.com, under the Investors section, or by calling 877-723-9521 (domestic) or 719-325-2138 (international). The access code is 9916080. A replay of the discussion will be available beginning at approximately 8:30 a.m. PT / 11:30 a.m. ET today from Seattle Genetics’ website or by calling 888-203-1112 (domestic) or 719-457-0820 (international), using access code 9916080. The telephone replay will be available until 5:00 p.m. PT / 8:00 p.m. ET Wednesday, June 28, 2017.
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 ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials in CD30-expressing lymphomas, including three Phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma, the completed ALCANZA trial in cutaneous T-cell lymphoma, and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas.
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 for intravenous injection has received approval from the FDA for three indications: (1) regular approval for the treatment of patients with classical Hodgkin lymphoma after failure of autologous hematopoietic stem cell transplantation (auto-HSCT) or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates, (2) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (3) accelerated approval for the treatment of patients with systemic anaplastic large cell lymphoma (sALCL) after failure of at least one prior multi-agent chemotherapy regimen. The sALCL indication is approved under accelerated approval based on overall response rate. Continued approval for the sALCL indication may be contingent upon verification and description of clinical benefit in confirmatory trials. Health Canada granted ADCETRIS approval with conditions for relapsed or refractory Hodgkin lymphoma and sALCL.
ADCETRIS was granted conditional marketing authorization by the European Commission in October 2012 for two indications: (1) for the treatment of adult patients with relapsed or refractory CD30-positive Hodgkin lymphoma following autologous stem cell transplant (ASCT), or following at least two prior therapies when ASCT or multi-agent chemotherapy is not a treatment option, and (2) the treatment of adult patients with relapsed or refractory sALCL.
In June 2016, the European Commission extended the current conditional approval of ADCETRIS and approved ADCETRIS for the treatment of adult patients with CD30-positive Hodgkin lymphoma at increased risk of relapse or progression following ASCT.
ADCETRIS has received marketing authorization by regulatory authorities in 67 countries for relapsed or refractory Hodgkin lymphoma and sALCL. See important safety information 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.
About Takeda
Takeda Pharmaceutical Company Limited 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 central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.
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.
About Seattle Genetics
Seattle Genetics is an innovative biotechnology company that develops and commercializes novel antibody-based therapies for the treatment of cancer. The company’s industry-leading antibody-drug conjugate (ADC) technology harnesses the targeting ability of antibodies to deliver cell-killing agents directly to cancer cells. ADCETRIS® (brentuximab vedotin), the company’s lead product, in collaboration with Takeda Pharmaceutical Company Limited, is the first in a new class of ADCs commercially available globally in 67 countries for relapsed classical Hodgkin lymphoma and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing enfortumab vedotin, an ADC for metastatic urothelial cancer, in a planned pivotal trial in collaboration with Astellas. Headquartered in Bothell, Washington, Seattle Genetics has a robust pipeline of innovative therapies for blood-related cancers and solid tumors designed to address significant unmet medical needs and improve treatment outcomes for patients. The company has collaborations for its proprietary ADC technology with a number of companies including AbbVie, Astellas, Bayer, Celldex, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com
SOURCE: Takeda Pharmaceutical Co
Post Views: 46
