-Phase 1 Clinical Data Featured in Press Program and Oral Presentation Demonstrate 76 Percent Objective Response Rate, Including a 41 Percent Complete Remission Rate, in Newly Diagnosed AML Patients Treated with 33A Combination Therapy-
-Data Support Recently Initiated Phase 3 CASCADE Study Evaluating 33A in Combination with Hypomethylating Agents in AML Patients-
COPENHAGEN, Denmark I June 11, 2016 I Seattle Genetics, Inc. (SGEN) today highlighted data at the 21st Congress of the European Hematology Association (EHA) taking place in Copenhagen, Denmark, June 9-12, 2016, evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with hypomethylating agents (HMAs; azacitidine, decitabine) in frontline patients with acute myeloid leukemia (AML) who had declined intensive therapy. 33A is an investigational antibody-drug conjugate (ADC) targeted to CD33 utilizing Seattle Genetics’ newest technology, comprising an engineered cysteine antibody (EC-mAb) stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer. CD33 is expressed on leukemic blasts in nearly all AML patients with expression generally consistent regardless of age, cytogenetic abnormalities or underlying mutations.
Based on data from the ongoing phase 1 clinical trial, a phase 3 clinical trial, called CASCADE, was recently initiated evaluating 33A in combination with HMAs in previously untreated AML patients not candidates for intensive induction chemotherapy. Seattle Genetics is also evaluating 33A broadly across multiple lines of therapy in patients with myeloid malignancies, including ongoing and planned phase 1 and 2 clinical trials for newly diagnosed or relapsed AML and for previously untreated myelodysplastic syndrome (MDS). More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.
“Hypomethylating agents, or HMAs, are the current standard of care for AML patients who are not able to tolerate intensive therapy. HMAs have limited benefit, with low response rates and median overall survival of 10 months or less,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “We believe that adding 33A to HMAs may improve efficacy and has the potential to redefine the treatment of AML. The clinical data at ASH showing high response rate, manageable tolerability profile and low early mortality reported have been maintained in this larger data set, and support our recently initiated phase 3 CASCADE clinical trial, which is now enrolling patients.”
“There is a dire need to improve outcomes for patients with AML,” said Amir Fathi, M.D., investigator of the phase 1 trial who will present the data at EHA. “The anti-leukemic activity we have observed in the phase 1 clinical trial evaluating 33A combination therapy in AML patients continues to be encouraging. This is an incredibly difficult disease to treat and the results to-date continue to show a balance of activity and tolerability together with low early mortality rates. The data presented suggest that the addition of 33A improves the rates of response and durable remissions in comparison to that seen historically from using the current standard of care alone.”
SGN-CD33A in Combination with Hypomethylating Agents: A Novel, Well-Tolerated Regimen with High Remission Rate in Older Patients with AML (Abstract #S503, oral presentation on Saturday, June 11, 2016 at 4:30 p.m. CEST)
Outcomes for AML patients who are not candidates for intensive chemotherapy or allogeneic stem cell transplant are dismal. Low intensity treatment options, including HMAs (azacitidine and decitabine), are limited. Interim results from the first 25 patients in the ongoing phase 1 study evaluating 33A in combination with HMAs in frontline AML were presented at the 2015 American Society of Hematology (ASH) Annual Meeting and Exposition. Updated interim results from the ongoing phase 1 study were presented in an oral session at EHA.
Data were reported from 53 frontline unfit AML patients with a median age of 75 years and intermediate or adverse cytogenetic risk who had declined intensive therapy. Forty-five percent of patients had evidence of underlying myelodysplasia. Key findings presented by Dr. Fathi include:
- Of 49 efficacy-evaluable patients treated with 33A combined with either azacitidine or decitabine, the overall response rate was 76 percent. Complete remission (CR) or complete remission with incomplete platelet or neutrophil recovery (CRi) was observed in 35 patients (71 percent). The remission rate (CR+CRi) was similar between the two 33A and HMA combination treatment groups (71 percent combined with azacitidine and 72 percent combined with decitabine).
- Responses were observed in higher-risk patients, with remissions achieved in 16 of 22 patients (73 percent) with underlying myelodysplasia and 15 of 18 patients (83 percent) with adverse cytogenetics.
- Patients who achieved minimal residual disease included eight of 19 (42 percent) CR patients and five of 15 (33 percent) CRi patients.
- The median overall survival for all patients in the phase 1 trial is interim and expected to evolve. The estimated median overall survival for the first 25 patients enrolled in the study was 12.75 months, with a median follow-up of 12.58 months.
- Median relapse-free survival was 7.7 months (range, 0.0+ and 11.3+) with 27 patients (51 percent) remaining alive and on study as of last follow-up. The 30- and 60-day mortality rates were two and eight percent, respectively.
- The most common treatment-related adverse events of any grade occurring in 20 percent or more of patients were fatigue (57 percent), thrombocytopenia (53 percent), nausea (49 percent), febrile neutropenia (45 percent), and constipation and anemia (42 percent each). The most common Grade 3 or 4 treatment-emergent adverse events occurring in 20 percent or more of patients were febrile neutropenia, thrombocytopenia, neutropenia, anemia and fatigue.
About Acute Myeloid Leukemia
Acute myeloid leukemia, also called acute myelocytic leukemia or AML, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. AML is a cancer that starts in the cells that are supposed to mature into different types of blood cells. AML starts in the bone marrow (the interior part of bones, where new blood cells are made) and quickly moves into the blood. According to the American Cancer Society, in 2016 approximately 20,000 new cases of AML (mostly in adults) will be diagnosed and nearly 10,500 deaths will occur from AML (almost all will be in adults).
About Vadastuximab Talirine (SGN-CD33A)
Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells.
33A was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.
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 approved globally in more than 60 countries for relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing vadastuximab talirine (SGN-CD33A; 33A), an ADC in a phase 3 trial for acute myeloid leukemia. Headquartered in Bothell, Washington, Seattle Genetics is also advancing 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, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
SOURCE: Seattle Genetics
Post Views: 153
-Phase 1 Clinical Data Featured in Press Program and Oral Presentation Demonstrate 76 Percent Objective Response Rate, Including a 41 Percent Complete Remission Rate, in Newly Diagnosed AML Patients Treated with 33A Combination Therapy-
-Data Support Recently Initiated Phase 3 CASCADE Study Evaluating 33A in Combination with Hypomethylating Agents in AML Patients-
COPENHAGEN, Denmark I June 11, 2016 I Seattle Genetics, Inc. (SGEN) today highlighted data at the 21st Congress of the European Hematology Association (EHA) taking place in Copenhagen, Denmark, June 9-12, 2016, evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with hypomethylating agents (HMAs; azacitidine, decitabine) in frontline patients with acute myeloid leukemia (AML) who had declined intensive therapy. 33A is an investigational antibody-drug conjugate (ADC) targeted to CD33 utilizing Seattle Genetics’ newest technology, comprising an engineered cysteine antibody (EC-mAb) stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer. CD33 is expressed on leukemic blasts in nearly all AML patients with expression generally consistent regardless of age, cytogenetic abnormalities or underlying mutations.
Based on data from the ongoing phase 1 clinical trial, a phase 3 clinical trial, called CASCADE, was recently initiated evaluating 33A in combination with HMAs in previously untreated AML patients not candidates for intensive induction chemotherapy. Seattle Genetics is also evaluating 33A broadly across multiple lines of therapy in patients with myeloid malignancies, including ongoing and planned phase 1 and 2 clinical trials for newly diagnosed or relapsed AML and for previously untreated myelodysplastic syndrome (MDS). More information about 33A and ongoing clinical trials can be found at www.ADC-CD33.com.
“Hypomethylating agents, or HMAs, are the current standard of care for AML patients who are not able to tolerate intensive therapy. HMAs have limited benefit, with low response rates and median overall survival of 10 months or less,” said Jonathan Drachman, M.D., Chief Medical Officer and Executive Vice President, Research and Development at Seattle Genetics. “We believe that adding 33A to HMAs may improve efficacy and has the potential to redefine the treatment of AML. The clinical data at ASH showing high response rate, manageable tolerability profile and low early mortality reported have been maintained in this larger data set, and support our recently initiated phase 3 CASCADE clinical trial, which is now enrolling patients.”
“There is a dire need to improve outcomes for patients with AML,” said Amir Fathi, M.D., investigator of the phase 1 trial who will present the data at EHA. “The anti-leukemic activity we have observed in the phase 1 clinical trial evaluating 33A combination therapy in AML patients continues to be encouraging. This is an incredibly difficult disease to treat and the results to-date continue to show a balance of activity and tolerability together with low early mortality rates. The data presented suggest that the addition of 33A improves the rates of response and durable remissions in comparison to that seen historically from using the current standard of care alone.”
SGN-CD33A in Combination with Hypomethylating Agents: A Novel, Well-Tolerated Regimen with High Remission Rate in Older Patients with AML (Abstract #S503, oral presentation on Saturday, June 11, 2016 at 4:30 p.m. CEST)
Outcomes for AML patients who are not candidates for intensive chemotherapy or allogeneic stem cell transplant are dismal. Low intensity treatment options, including HMAs (azacitidine and decitabine), are limited. Interim results from the first 25 patients in the ongoing phase 1 study evaluating 33A in combination with HMAs in frontline AML were presented at the 2015 American Society of Hematology (ASH) Annual Meeting and Exposition. Updated interim results from the ongoing phase 1 study were presented in an oral session at EHA.
Data were reported from 53 frontline unfit AML patients with a median age of 75 years and intermediate or adverse cytogenetic risk who had declined intensive therapy. Forty-five percent of patients had evidence of underlying myelodysplasia. Key findings presented by Dr. Fathi include:
- Of 49 efficacy-evaluable patients treated with 33A combined with either azacitidine or decitabine, the overall response rate was 76 percent. Complete remission (CR) or complete remission with incomplete platelet or neutrophil recovery (CRi) was observed in 35 patients (71 percent). The remission rate (CR+CRi) was similar between the two 33A and HMA combination treatment groups (71 percent combined with azacitidine and 72 percent combined with decitabine).
- Responses were observed in higher-risk patients, with remissions achieved in 16 of 22 patients (73 percent) with underlying myelodysplasia and 15 of 18 patients (83 percent) with adverse cytogenetics.
- Patients who achieved minimal residual disease included eight of 19 (42 percent) CR patients and five of 15 (33 percent) CRi patients.
- The median overall survival for all patients in the phase 1 trial is interim and expected to evolve. The estimated median overall survival for the first 25 patients enrolled in the study was 12.75 months, with a median follow-up of 12.58 months.
- Median relapse-free survival was 7.7 months (range, 0.0+ and 11.3+) with 27 patients (51 percent) remaining alive and on study as of last follow-up. The 30- and 60-day mortality rates were two and eight percent, respectively.
- The most common treatment-related adverse events of any grade occurring in 20 percent or more of patients were fatigue (57 percent), thrombocytopenia (53 percent), nausea (49 percent), febrile neutropenia (45 percent), and constipation and anemia (42 percent each). The most common Grade 3 or 4 treatment-emergent adverse events occurring in 20 percent or more of patients were febrile neutropenia, thrombocytopenia, neutropenia, anemia and fatigue.
About Acute Myeloid Leukemia
Acute myeloid leukemia, also called acute myelocytic leukemia or AML, is an aggressive type of cancer of the bone marrow and blood that progresses rapidly without treatment. AML is a cancer that starts in the cells that are supposed to mature into different types of blood cells. AML starts in the bone marrow (the interior part of bones, where new blood cells are made) and quickly moves into the blood. According to the American Cancer Society, in 2016 approximately 20,000 new cases of AML (mostly in adults) will be diagnosed and nearly 10,500 deaths will occur from AML (almost all will be in adults).
About Vadastuximab Talirine (SGN-CD33A)
Vadastuximab talirine (SGN-CD33A; 33A) is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. CD33 is expressed on most AML and MDS blast cells. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The ADC is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells.
33A was granted Orphan Drug Designation by both the U.S. Food and Drug Administration (FDA) and the European Commission for the treatment of AML. FDA orphan drug designation is intended to encourage companies to develop therapies for the treatment of diseases that affect fewer than 200,000 individuals in the United States.
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 approved globally in more than 60 countries for relapsed classical Hodgkin lymphoma (HL) and relapsed systemic anaplastic large cell lymphoma (sALCL). Seattle Genetics is also advancing vadastuximab talirine (SGN-CD33A; 33A), an ADC in a phase 3 trial for acute myeloid leukemia. Headquartered in Bothell, Washington, Seattle Genetics is also advancing 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, Genentech, GlaxoSmithKline and Pfizer. More information can be found at www.seattlegenetics.com.
SOURCE: Seattle Genetics
Post Views: 153
