BLA Based on Clinical Trial Results from the Phase 3 ALCANZA and Phase 2 Investigator-Sponsored Studies in Cutaneous T-Cell Lymphoma
BOTHELL, WA, USA I June 20, 2017 I Seattle Genetics, Inc. (Nasdaq: SGEN) announced today that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). ADCETRIS is currently not approved for the treatment of CTCL.
“The submission of the supplemental BLA requesting label expansion for ADCETRIS as a treatment in CTCL patients who require systemic therapy is an important milestone. CTCL is an incurable and disfiguring disease in need of new therapeutic options, particularly those that achieve durable responses,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development of Seattle Genetics. “Results from the phase 3 ALCANZA trial demonstrated that CTCL patients treated with ADCETRIS had superior outcomes across all primary and secondary endpoints compared to patients in the control arm who were treated with either methotrexate or bexarotene standard of care agents. In addition to the ALCANZA results, data from two investigator-sponsored trials also support ADCETRIS use in this disease setting. We believe these data are clinically meaningful and support a label expansion for ADCETRIS in CTCL, which would be the fourth indication for this program.”
In November 2016, based on preliminary analysis of ALCANZA, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These represent the most common subtypes of CTCL. Based on discussions with the FDA following the BTD, additional data from investigator-sponsored phase 2 trials have been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.
The supplemental BLA is primarily based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) annual meeting in December 2016 and published in the Lancet in June 2017. Results from the ALCANZA trial in 128 CTCL patients requiring systemic therapy included:
- The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001).
- Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm.
- The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.
About CTCL
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. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.
The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma, from which data were submitted in a supplemental BLA.
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-positive 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. 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 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 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 and is commercially available globally in 67 countries for relapsed classical Hodgkin lymphoma (HL) 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 and with European and international operations in Zug, Switzerland, 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: Seattle Genetics
Post Views: 163
BLA Based on Clinical Trial Results from the Phase 3 ALCANZA and Phase 2 Investigator-Sponsored Studies in Cutaneous T-Cell Lymphoma
BOTHELL, WA, USA I June 20, 2017 I Seattle Genetics, Inc. (Nasdaq: SGEN) announced today that it has submitted a supplemental Biologics License Application (BLA) to the U.S. Food and Drug Administration (FDA) based on data from the phase 3 ALCANZA trial and two phase 2 investigator-sponsored trials of ADCETRIS (brentuximab vedotin) in patients with cutaneous T-cell lymphoma (CTCL). ADCETRIS is currently not approved for the treatment of CTCL.
“The submission of the supplemental BLA requesting label expansion for ADCETRIS as a treatment in CTCL patients who require systemic therapy is an important milestone. CTCL is an incurable and disfiguring disease in need of new therapeutic options, particularly those that achieve durable responses,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development of Seattle Genetics. “Results from the phase 3 ALCANZA trial demonstrated that CTCL patients treated with ADCETRIS had superior outcomes across all primary and secondary endpoints compared to patients in the control arm who were treated with either methotrexate or bexarotene standard of care agents. In addition to the ALCANZA results, data from two investigator-sponsored trials also support ADCETRIS use in this disease setting. We believe these data are clinically meaningful and support a label expansion for ADCETRIS in CTCL, which would be the fourth indication for this program.”
In November 2016, based on preliminary analysis of ALCANZA, the FDA granted ADCETRIS Breakthrough Therapy Designation (BTD) for the treatment of patients with CD30-expressing mycosis fungoides and primary cutaneous anaplastic large cell lymphoma who require systemic therapy and have received one prior systemic therapy. These represent the most common subtypes of CTCL. Based on discussions with the FDA following the BTD, additional data from investigator-sponsored phase 2 trials have been incorporated into the supplemental BLA to support the potential for a broader label in CTCL.
The supplemental BLA is primarily based on positive results from a phase 3 trial called ALCANZA that were presented at the 58th American Society of Hematology (ASH) annual meeting in December 2016 and published in the Lancet in June 2017. Results from the ALCANZA trial in 128 CTCL patients requiring systemic therapy included:
- The trial achieved its primary endpoint with the ADCETRIS treatment arm demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4) versus the control arm as assessed by an independent review facility. ORR4, as assessed by Global Response Score, was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm (p-value <0.0001).
- Key secondary endpoints specified in the protocol, including complete response rate, progression-free survival and reduction in the burden of symptoms during treatment (Skindex-29), were all highly statistically significant in favor of the ADCETRIS arm.
- The safety profile associated with ADCETRIS from the ALCANZA trial was generally consistent with the existing prescribing information. The most common adverse events of any grade include: peripheral neuropathy, nausea, diarrhea, fatigue, vomiting, alopecia, pruritis, pyrexia, decreased appetite and hypertriglyceridemia.
About CTCL
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. Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. According to the Cutaneous Lymphoma Foundation, CTCL is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. Progression from limited skin involvement may be accompanied by skin tumor formation, ulceration and exfoliation, complicated by itching and infections. Advanced stages are defined by involvement of lymph nodes, peripheral blood and internal organs.
The standard treatment for systemically pretreated CTCL includes skin-directed therapies, radiation and systemic therapies. The systemic therapies currently approved for treatment have demonstrated 30 to 45 percent objective response rates, with low complete response rates.
About ADCETRIS
ADCETRIS is being evaluated broadly in more than 70 ongoing clinical trials, including three Phase 3 studies, the ongoing ECHELON-1 trial in frontline classical Hodgkin lymphoma and the ongoing ECHELON-2 trial in frontline mature T-cell lymphomas, as well as the completed ALCANZA trial in cutaneous T-cell lymphoma, from which data were submitted in a supplemental BLA.
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-positive 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. 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 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 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 and is commercially available globally in 67 countries for relapsed classical Hodgkin lymphoma (HL) 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 and with European and international operations in Zug, Switzerland, 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: Seattle Genetics
Post Views: 163
