- Data Supported FDA Accelerated Approval in Relapsed Patients-
- Broad Ongoing Evaluation of ADCETRIS in Earlier Lines of Hodgkin Lymphoma and in Other CD30-Positive Malignancies-
BOTHELL, WA, USA I March 26, 2012 I Seattle Genetics, Inc. (Nasdaq:SGEN – News) today announced that the Journal of Clinical Oncology (JCO) published results of the company’s pivotal clinical trial of ADCETRIS™ (brentuximab vedotin) in Hodgkin lymphoma (HL) patients with relapsed or refractory disease following an autologous stem cell transplant (ASCT). The findings, published today online, demonstrated that treatment with ADCETRIS as a single agent induced durable objective responses in 75 percent of patients and was associated with a manageable safety profile. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in HL and anaplastic large cell lymphoma (ALCL).
Additionally, a separate pivotal clinical trial of ADCETRIS for the treatment of relapsed or refractory systemic ALCL has been accepted for publication and is currently in press for an upcoming issue of JCO.
“Although Hodgkin lymphoma is often viewed as a curable disease, up to 30 percent of patients relapse or are refractory following front-line chemotherapy regimens and subsequent treatments, leaving limited therapeutic options,” said Dr. Anas Younes, Professor of Medicine and Director, Clinical Investigation and Translational Research Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “ADCETRIS represents a new approach that is changing the way we treat relapsed and refractory HL patients. The complete response rate and manageable safety profile we observed with ADCETRIS in the pivotal trial have also generated enthusiasm among the medical community for evaluating ADCETRIS in earlier lines of HL therapy.”
“Data from this pivotal trial served as the basis for the accelerated approval of ADCETRIS in August 2011 for relapsed Hodgkin patients, and is the foundation for our robust clinical development plan to broadly evaluate ADCETRIS in earlier lines of therapy, as well as in other CD30-positive malignancies,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. “We are evaluating ADCETRIS across a broad array of CD30-positive malignancies, towards our goal of bringing it to additional patients in need.”
The open-label, phase II study evaluated the efficacy and safety of ADCETRIS in 102 patients with relapsed or refractory, CD30-positive HL after ASCT.
Highlights from the study include:
75 percent of patients achieved an objective response, the primary endpoint of the trial, as assessed by an independent central review.
34 percent of patients achieved a complete remission.
The median duration of response was 29 weeks by independent central review, and 47 weeks by investigator assessment. Durable complete remissions approaching two years were observed.
Treatment with ADCETRIS was associated with manageable adverse events, the most common being peripheral sensory neuropathy, nausea, fatigue, neutropenia and diarrhea. The most common Grade 3 or higher adverse events were neutropenia, peripheral sensory neuropathy, thrombocytopenia and anemia.
About ADCETRIS
ADCETRIS (brentuximab vedotin) 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 is being evaluated in a phase III clinical trial (the AETHERA trial) for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant (ASCT), a phase II trial for relapsed or refractory CD30-positive non-Hodgkin lymphomas, a phase II trial for CD30-positive non-lymphoma malignancies, a phase II retreatment trial for relapsed patients who previously responded to ADCETRIS, a phase I trial in combination with multi-agent chemotherapy for front-line treatment of Hodgkin lymphoma and a phase I trial in combination with multi-agent chemotherapy for front-line treatment of mature T-cell lymphomas. Three additional phase III trials are planned, including a trial in CD30-positive cutaneous T-cell lymphomas to begin in mid-2012, a front-line trial in Hodgkin lymphoma and a front-line trial in mature T-cell lymphomas. The front-line trials are expected to begin by late 2012 or early 2013.
Seattle Genetics and Millennium: The Takeda Oncology Company are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group is solely responsible for development costs.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The FDA granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at www.seattlegenetics.com.
U.S. Important Safety Information
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS.
Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.
Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Drug Interactions:
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.
SOURCE: Seattle Genetics
Post Views: 31
- Data Supported FDA Accelerated Approval in Relapsed Patients-
- Broad Ongoing Evaluation of ADCETRIS in Earlier Lines of Hodgkin Lymphoma and in Other CD30-Positive Malignancies-
BOTHELL, WA, USA I March 26, 2012 I Seattle Genetics, Inc. (Nasdaq:SGEN – News) today announced that the Journal of Clinical Oncology (JCO) published results of the company’s pivotal clinical trial of ADCETRIS™ (brentuximab vedotin) in Hodgkin lymphoma (HL) patients with relapsed or refractory disease following an autologous stem cell transplant (ASCT). The findings, published today online, demonstrated that treatment with ADCETRIS as a single agent induced durable objective responses in 75 percent of patients and was associated with a manageable safety profile. ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, which is expressed in HL and anaplastic large cell lymphoma (ALCL).
Additionally, a separate pivotal clinical trial of ADCETRIS for the treatment of relapsed or refractory systemic ALCL has been accepted for publication and is currently in press for an upcoming issue of JCO.
“Although Hodgkin lymphoma is often viewed as a curable disease, up to 30 percent of patients relapse or are refractory following front-line chemotherapy regimens and subsequent treatments, leaving limited therapeutic options,” said Dr. Anas Younes, Professor of Medicine and Director, Clinical Investigation and Translational Research Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “ADCETRIS represents a new approach that is changing the way we treat relapsed and refractory HL patients. The complete response rate and manageable safety profile we observed with ADCETRIS in the pivotal trial have also generated enthusiasm among the medical community for evaluating ADCETRIS in earlier lines of HL therapy.”
“Data from this pivotal trial served as the basis for the accelerated approval of ADCETRIS in August 2011 for relapsed Hodgkin patients, and is the foundation for our robust clinical development plan to broadly evaluate ADCETRIS in earlier lines of therapy, as well as in other CD30-positive malignancies,” said Thomas C. Reynolds, M.D., Ph.D., Chief Medical Officer of Seattle Genetics. “We are evaluating ADCETRIS across a broad array of CD30-positive malignancies, towards our goal of bringing it to additional patients in need.”
The open-label, phase II study evaluated the efficacy and safety of ADCETRIS in 102 patients with relapsed or refractory, CD30-positive HL after ASCT.
Highlights from the study include:
75 percent of patients achieved an objective response, the primary endpoint of the trial, as assessed by an independent central review.
34 percent of patients achieved a complete remission.
The median duration of response was 29 weeks by independent central review, and 47 weeks by investigator assessment. Durable complete remissions approaching two years were observed.
Treatment with ADCETRIS was associated with manageable adverse events, the most common being peripheral sensory neuropathy, nausea, fatigue, neutropenia and diarrhea. The most common Grade 3 or higher adverse events were neutropenia, peripheral sensory neuropathy, thrombocytopenia and anemia.
About ADCETRIS
ADCETRIS (brentuximab vedotin) 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 is being evaluated in a phase III clinical trial (the AETHERA trial) for patients at high risk of residual Hodgkin lymphoma following autologous stem cell transplant (ASCT), a phase II trial for relapsed or refractory CD30-positive non-Hodgkin lymphomas, a phase II trial for CD30-positive non-lymphoma malignancies, a phase II retreatment trial for relapsed patients who previously responded to ADCETRIS, a phase I trial in combination with multi-agent chemotherapy for front-line treatment of Hodgkin lymphoma and a phase I trial in combination with multi-agent chemotherapy for front-line treatment of mature T-cell lymphomas. Three additional phase III trials are planned, including a trial in CD30-positive cutaneous T-cell lymphomas to begin in mid-2012, a front-line trial in Hodgkin lymphoma and a front-line trial in mature T-cell lymphomas. The front-line trials are expected to begin by late 2012 or early 2013.
Seattle Genetics and Millennium: The Takeda Oncology Company are jointly developing ADCETRIS. Under the terms of the collaboration agreement, Seattle Genetics has U.S. and Canadian commercialization rights and the Takeda Group has rights to commercialize ADCETRIS in the rest of the world. Seattle Genetics and the Takeda Group are funding joint development costs for ADCETRIS on a 50:50 basis, except in Japan where the Takeda Group is solely responsible for development costs.
About Seattle Genetics
Seattle Genetics is a biotechnology company focused on the development and commercialization of monoclonal antibody-based therapies for the treatment of cancer. The FDA granted accelerated approval of ADCETRIS in August 2011 for two indications. ADCETRIS is being developed in collaboration with Millennium: The Takeda Oncology Company. In addition, Seattle Genetics has three other clinical-stage ADC programs: SGN-75, ASG-5ME and ASG-22ME. Seattle Genetics has collaborations for its ADC technology with a number of leading biotechnology and pharmaceutical companies, including Abbott, Bayer, Celldex Therapeutics, Daiichi Sankyo, Genentech, GlaxoSmithKline, Millennium, Pfizer and Progenics, as well as ADC co-development agreements with Agensys, an affiliate of Astellas, and Genmab. More information can be found at www.seattlegenetics.com.
U.S. Important Safety Information
BOXED WARNING
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death can occur in patients receiving ADCETRIS.
Contraindication:
Concomitant use of ADCETRIS and bleomycin is contraindicated due to pulmonary toxicity.
Warnings and Precautions:
Peripheral neuropathy: ADCETRIS treatment causes a peripheral neuropathy that is predominantly sensory. Cases of peripheral motor neuropathy have also been reported. ADCETRIS-induced peripheral neuropathy is cumulative. Treating physicians should monitor patients for symptoms of neuropathy, such as hypoesthesia, hyperesthesia, paresthesia, discomfort, a burning sensation, neuropathic pain or weakness and institute dose modifications accordingly.
Infusion reactions: Infusion-related reactions, including anaphylaxis, have occurred with ADCETRIS. Monitor patients during infusion. If an infusion reaction occurs, the infusion should be interrupted and appropriate medical management instituted. If anaphylaxis occurs, the infusion should be immediately and permanently discontinued and appropriate medical management instituted.
Neutropenia: Monitor complete blood counts prior to each dose of ADCETRIS and consider more frequent monitoring for patients with Grade 3 or 4 neutropenia. If Grade 3 or 4 neutropenia develops, manage by dose delays, reductions or discontinuation. Prolonged (≥1 week) severe neutropenia can occur with ADCETRIS.
Tumor lysis syndrome: Patients with rapidly proliferating tumor and high tumor burden are at risk of tumor lysis syndrome and these patients should be monitored closely and appropriate measures taken.
Progressive multifocal leukoencephalopathy (PML): JC virus infection resulting in PML and death has been reported in ADCETRIS-treated patients. In addition to ADCETRIS therapy, other possible contributory factors include prior therapies and underlying disease that may cause immunosuppression. Consider the diagnosis of PML in any patient presenting with new-onset signs and symptoms of central nervous system abnormalities. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture or brain biopsy. Hold ADCETRIS if PML is suspected and discontinue ADCETRIS if PML is confirmed.
Stevens-Johnson syndrome: Stevens-Johnson syndrome has been reported with ADCETRIS. If Stevens-Johnson syndrome occurs, discontinue ADCETRIS and administer appropriate medical therapy.
Use in pregnancy: Fetal harm can occur. Pregnant women should be advised of the potential hazard to the fetus.
Adverse Reactions:
ADCETRIS was studied as monotherapy in 160 patients in two phase 2 trials. Across both trials, the most common adverse reactions (≥20%), regardless of causality, were neutropenia, peripheral sensory neuropathy, fatigue, nausea, anemia, upper respiratory tract infection, diarrhea, pyrexia, rash, thrombocytopenia, cough and vomiting.
Drug Interactions:
Patients who are receiving strong CYP3A4 inhibitors concomitantly with ADCETRIS should be closely monitored for adverse reactions.
For additional important safety information, including Boxed WARNING, please see the full U.S. prescribing information for ADCETRIS at www.seattlegenetics.com or www.ADCETRIS.com.
SOURCE: Seattle Genetics
Post Views: 31
