-PDUFA Action Date May 1, 2018-
-Submission Based on Positive Results from the Phase 3 ECHELON-1 Clinical Trial-
-FDA Previously Granted Breakthrough Therapy Designation for ADCETRIS in Frontline Advanced Hodgkin Lymphoma-
BOTHELL, WA, USA I January 2, 2018 I Seattle Genetics, Inc. (NASDAQ:SGEN) announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental Biologics License Application (BLA) for ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with advanced classical Hodgkin lymphoma. The FDA granted Priority Review for the application, and the Prescription Drug User Fee Act (PDUFA) target action date is May 1, 2018. The submission of the supplemental BLA is based on positive results from a phase 3 clinical trial called ECHELON-1 that was designed to determine if ADCETRIS in combination with chemotherapy could extend modified progression-free survival (modified PFS) in previously untreated advanced classical Hodgkin lymphoma patients. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma. ADCETRIS is being evaluated globally as the foundation of care for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials. ADCETRIS is currently not approved as a frontline therapy for Hodgkin lymphoma.
“The FDA’s filing of our supplemental BLA with Priority Review represents a significant milestone in our goal to redefine the frontline treatment of advanced Hodgkin lymphoma,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We recently reported the primary data from the phase 3 ECHELON-1 clinical trial in the Plenary Scientific Session of the 2017 ASH Annual Meeting with simultaneous publication in the New England Journal of Medicine. The data demonstrated superior activity of the ADCETRIS-containing regimen over standard of care, and we are working with the FDA to make this bleomycin-free regimen available to newly diagnosed advanced Hodgkin lymphoma patients as soon as possible.”
In October 2017, the FDA granted ADCETRIS Breakthrough Therapy Designation based on the ECHELON-1 study results. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies in one or more clinically significant endpoints.
The ECHELON-1 study evaluated a combination of ADCETRIS plus AVD (Adriamycin, vinblastine, dacarbazine) compared to a recognized standard of care chemotherapy regimen, ABVD (which includes bleomycin), in frontline advanced classical Hodgkin lymphoma. The positive results from the phase 3 ECHELON-1 trial were featured in the Plenary Scientific Session of the 59th American Society of Hematology (ASH) Annual Meeting with simultaneous publication in the New England Journal of Medicine in December 2017. Results from the ECHELON-1 trial in 1,334 Hodgkin lymphoma patients included:
- The trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by an Independent Review Facility (IRF) (p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death or need for additional anticancer therapy. Per IRF assessment, the two-year modified PFS rate for patients in the ADCETRIS plus AVD arm was 82.1 percent compared to 77.2 percent in the control arm.
- The investigator assessment of modified PFS also demonstrated a statistically significant advantage for ADCETRIS plus AVD versus the control arm of ABVD (p-value <0.01).
- All secondary endpoints, including interim analysis of overall survival, trended in favor of the ADCETRIS plus AVD arm.
- The safety profile of ADCETRIS plus AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen.
ECHELON-1 Phase 3 Clinical Trial Design
The randomized, open-label, phase 3 trial is investigating ADCETRIS plus AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma. The primary endpoint is modified PFS 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. 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 was conducted under a Special Protocol Assessment (SPA) agreement from the FDA and the trial also received EMA scientific advice.
Please see Important Safety Information at the end of this press release.
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. Although the currently used standard of care frontline combination chemotherapy can result in durable responses, up to 30 percent of patients with advanced Hodgkin lymphoma relapse or are refractory to frontline treatment.
According to the American Cancer Society, approximately 8,260 cases of Hodgkin lymphoma will be diagnosed in the United States during 2017 and more than 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people (including early and advanced stage) worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin 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 four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) 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, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) 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 in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
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. The European Commission extended the current conditional marketing authorization 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 70 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 Seattle Genetics
Seattle Genetics is an innovative biotechnology company dedicated to improving the lives of people with cancer through novel antibody-based therapies. 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. Seattle Genetics commercializes ADCETRIS® (brentuximab vedotin) for the treatment of several types of CD30-expressing lymphomas. The company is also advancing a robust pipeline of novel therapies for solid tumors and blood-related cancers designed to address significant unmet medical needs and improve treatment outcomes for patients. More information can be found at www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
SOURCE: Seattle Genetics
Post Views: 25
-PDUFA Action Date May 1, 2018-
-Submission Based on Positive Results from the Phase 3 ECHELON-1 Clinical Trial-
-FDA Previously Granted Breakthrough Therapy Designation for ADCETRIS in Frontline Advanced Hodgkin Lymphoma-
BOTHELL, WA, USA I January 2, 2018 I Seattle Genetics, Inc. (NASDAQ:SGEN) announced today that the U.S. Food and Drug Administration (FDA) has accepted for filing a supplemental Biologics License Application (BLA) for ADCETRIS (brentuximab vedotin) in combination with chemotherapy for the frontline treatment of patients with advanced classical Hodgkin lymphoma. The FDA granted Priority Review for the application, and the Prescription Drug User Fee Act (PDUFA) target action date is May 1, 2018. The submission of the supplemental BLA is based on positive results from a phase 3 clinical trial called ECHELON-1 that was designed to determine if ADCETRIS in combination with chemotherapy could extend modified progression-free survival (modified PFS) in previously untreated advanced classical Hodgkin lymphoma patients. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, a defining marker of classical Hodgkin lymphoma. ADCETRIS is being evaluated globally as the foundation of care for CD30-expressing lymphomas in more than 70 corporate- and investigator-sponsored clinical trials. ADCETRIS is currently not approved as a frontline therapy for Hodgkin lymphoma.
“The FDA’s filing of our supplemental BLA with Priority Review represents a significant milestone in our goal to redefine the frontline treatment of advanced Hodgkin lymphoma,” said Clay Siegall, Ph.D., President and Chief Executive Officer of Seattle Genetics. “We recently reported the primary data from the phase 3 ECHELON-1 clinical trial in the Plenary Scientific Session of the 2017 ASH Annual Meeting with simultaneous publication in the New England Journal of Medicine. The data demonstrated superior activity of the ADCETRIS-containing regimen over standard of care, and we are working with the FDA to make this bleomycin-free regimen available to newly diagnosed advanced Hodgkin lymphoma patients as soon as possible.”
In October 2017, the FDA granted ADCETRIS Breakthrough Therapy Designation based on the ECHELON-1 study results. The FDA’s Breakthrough Therapy Designation is intended to expedite the development and review of promising drug candidates for serious or life-threatening conditions. It is based upon clinical evidence of substantial improvement over existing therapies in one or more clinically significant endpoints.
The ECHELON-1 study evaluated a combination of ADCETRIS plus AVD (Adriamycin, vinblastine, dacarbazine) compared to a recognized standard of care chemotherapy regimen, ABVD (which includes bleomycin), in frontline advanced classical Hodgkin lymphoma. The positive results from the phase 3 ECHELON-1 trial were featured in the Plenary Scientific Session of the 59th American Society of Hematology (ASH) Annual Meeting with simultaneous publication in the New England Journal of Medicine in December 2017. Results from the ECHELON-1 trial in 1,334 Hodgkin lymphoma patients included:
- The trial achieved its primary endpoint with the combination of ADCETRIS plus AVD resulting in a statistically significant improvement in modified PFS versus the control arm of ABVD as assessed by an Independent Review Facility (IRF) (p-value=0.035). This corresponds to a 23 percent reduction in the risk of progression, death or need for additional anticancer therapy. Per IRF assessment, the two-year modified PFS rate for patients in the ADCETRIS plus AVD arm was 82.1 percent compared to 77.2 percent in the control arm.
- The investigator assessment of modified PFS also demonstrated a statistically significant advantage for ADCETRIS plus AVD versus the control arm of ABVD (p-value <0.01).
- All secondary endpoints, including interim analysis of overall survival, trended in favor of the ADCETRIS plus AVD arm.
- The safety profile of ADCETRIS plus AVD in the ECHELON-1 trial was generally consistent with that known for the single-agent components of the regimen.
ECHELON-1 Phase 3 Clinical Trial Design
The randomized, open-label, phase 3 trial is investigating ADCETRIS plus AVD versus ABVD as frontline therapy in patients with advanced classical Hodgkin lymphoma. The primary endpoint is modified PFS 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. 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 was conducted under a Special Protocol Assessment (SPA) agreement from the FDA and the trial also received EMA scientific advice.
Please see Important Safety Information at the end of this press release.
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. Although the currently used standard of care frontline combination chemotherapy can result in durable responses, up to 30 percent of patients with advanced Hodgkin lymphoma relapse or are refractory to frontline treatment.
According to the American Cancer Society, approximately 8,260 cases of Hodgkin lymphoma will be diagnosed in the United States during 2017 and more than 1,000 will die from the disease. According to the Lymphoma Coalition, over 62,000 people (including early and advanced stage) worldwide are diagnosed with Hodgkin lymphoma each year and approximately 25,000 people die each year from this cancer.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 clinical trials, including three phase 3 studies: the completed ECHELON-1 trial in frontline classical Hodgkin lymphoma that supported the recent FDA Breakthrough Therapy Designation and submission of the supplemental Biologics License Application (BLA) for use in this setting, the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, and the ongoing CHECKMATE 812 trial of ADCETRIS in combination with Opdivo (nivolumab) for relapsed/refractory Hodgkin 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 four indications: (1) regular approval for adult patients with primary cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing mycosis fungoides (MF) who have received prior systemic therapy, (2) 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, (3) regular approval for the treatment of classical Hodgkin lymphoma patients at high risk of relapse or progression as post-auto-HSCT consolidation, and (4) 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 in 2013, and non-conditional approval for post-ASCT consolidation treatment of Hodgkin lymphoma patients at increased risk of relapse or progression.
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. The European Commission extended the current conditional marketing authorization 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 70 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 Seattle Genetics
Seattle Genetics is an innovative biotechnology company dedicated to improving the lives of people with cancer through novel antibody-based therapies. 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. Seattle Genetics commercializes ADCETRIS® (brentuximab vedotin) for the treatment of several types of CD30-expressing lymphomas. The company is also advancing a robust pipeline of novel therapies for solid tumors and blood-related cancers designed to address significant unmet medical needs and improve treatment outcomes for patients. More information can be found at www.seattlegenetics.com and follow @SeattleGenetics on Twitter.
SOURCE: Seattle Genetics
Post Views: 25
