The primary and secondary endpoints were met. Non-inferiority to pegfilgrastim therapy was established
SHANGHAI, China I December 8, 2014 I Generon (Shanghai) Corporation, a leading biopharmaceutical company in China, today announced the presentation of the global Phase II study results for F-627 (benegrastim) at the American Society of Hematology (ASH®) 56th Annual Meeting at San Francisco entitled “Phase II, Randomized, Multi-Center, Open-Label, Active Controlled, Dose Finding Trial of F-627 (benegrastim) in Women with Breast Cancer Receiving Mylotoxic Chemotherapy” (poster #1584). Benegrastim demonstrated non-inferiority for the duration of moderate and severe neutropenia as compared to pegfilgrastim (Neulasta®) in patients with Stage I-IV breast cancer who received docetaxel / cyclophosphamide (TC) or Doxorubicin / docetaxel / cyclophosphamide (TAC) chemotherapy.
In the Phase II trial, 232 breast cancer patients were enrolled in 35 centers in the US and Eastern Europe. Each patient was scheduled to undergo four (21-day) chemotherapy cycles. Patients were randomized to receive F-627 or pegfilgrastim (6 mg fixed dose) one day after receiving their chemotherapy, for each cycle, as a subcutaneous injection. Three dose levels of F-627 (80, 240, and 320 μg/kg) vs. pegfilgrastim were tested in patients receiving the TC regimen, with a randomization ratio of 1:1:1:1. Two dose levels of F-627 (240 and 320 μg/kg) vs. pegfilgrastim were tested in patients receiving the TAC regimen, with a randomization ratio of 1:1:1. In this study, 141 patients received TC chemotherapy and 91 patients received TAC chemotherapy.
The primary efficacy endpoint of this study was the duration of grade 3 (moderate) and grade 4 (severe) neutropenia, defined as an ANC < 1.0 × 109/L, during the first cycle of chemotherapy. Secondary endpoints included the duration of grade 4 (severe) neutropenia, defined as an ANC < 0.5 × 109/L, for each chemotherapy cycle, evaluation of nadir depth for each chemotherapy cycle, the incidence rate of febrile neutropenia, and time to ANC recovery, defined as an ANC ≥ 2.0 × 109/L post nadir, for each chemotherapy cycle. For patients receiving the TC chemotherapy regimen, the mean difference in the duration of moderate and severe neutropenia in the Intent to Treat Population (ITT) for patients receiving benegrastim as compared to pegfilgrastim was 0.4 days for the 80 μg/kg group with a 95% CI (-0.1, 0.9), 0.3 days for the 240 μg/kg group with a 95% CI (-0.2, 0.8) and 0.3 days for the 320 μg/kg group with a 95% CI (-0.2, 0.9). For patients receiving the TAC chemotherapy regimen, the mean difference in the duration of moderate and severe neutropenia in the ITT for patients receiving benegrastim as compared to pegfilgrastim was 0.3 days for the 240 μg/kg group with a 95% CI (-0.5, 1.1) and 0.4 days for the 320 μg/kg group with a 95% CI (-0.4, 1.2). The secondary objective results for the 240 and 320 μg/kg benegrastim doses were also comparable to pegfilgrastim. The pre-specified non-inferiority margin of 2 days was met from all benegrastim doses in both TC and TAC groups, and was consistent from analysis of the ITT as well as the Per-protocol (PP) analysis populations.
The safety profiles of all doses of benegrastim were similar to that of pegfilgrastim. Two cases of febrile neutropenia were reported in the 320 μg/kg group and 2 cases were reported in the pegfilgrastim group. Three serious adverse events (SAEs) were reported from the combined benegrastim groups, 7 SAEs were reported from the pegfilgrastim group. Adverse events (AEs) coded under Infections and Infestations were reported for 8.6, 4.5 and 3.1% of the patients from the 80, 240, and 320 μg/kg benegrastim dose groups, respectively. Comparably, 9.2% of the patients from the pegfilgrastim group reported AEs coded under Infections and Infestations. No deaths were reported in this study.
Dr. J. Glaspy at UCLA Medical Center congratulated the Generon team and commented: “F-627 is a promising alternative treatment for chemo-induced neutropenia patients. The study was well conducted for a study this size to show non-inferiority.”
Dr. David Lacey, Chairman of the Scientific Advisory Board of Generon, also commented “The Ph II data for Generon’s F-627 that shows non-inferiority to the segment leader Neulasta (R) continues to support the promise of this novel, G-CSF-based therapeutic for use in settings where the risk of chemotherapy-induced febrile neutropenia is appreciable. This molecule presents G-CSF as a dimer and its prolonged half-life is in part due to recombinant fusion with human Fc. These data strongly support the continued development of F-627 for use in settings where myelotoxic therapies are deployed.”
Dr. Yuliang Huang, CEO of Generon said “We are extremely pleased about the exciting Phase II study results of benegrastim. This demonstrated our commitment of ‘innovating for life’ to bring innovative biologicals to patients in China and worldwide. Benegrastim allows us to compete in the approximately $7 billion global market.”
About Benegrastim
Benegrastim (F-627) is a rhG-CSF dimer (rhG-CSF-Fc fusion protein), a third generation recombinant human granulocyte colony-stimulating factor (G-CSF). Benegrastim is expressed as a dimer in mammalian cells. Benegrastim could potentially generate a quicker neutrophil recovery after chemotherapy and help physicians manage severe neutropenia.
About Generon (Shanghai) Corporation
Generon (Shanghai) Corporation (Generon) is a leading biopharmaceutical company located in China focusing on development of innovative biological therapies for global patients. For more information, please visit http://www.generonbiomed.com.
SOURCE: Generon
Post Views: 139
The primary and secondary endpoints were met. Non-inferiority to pegfilgrastim therapy was established
SHANGHAI, China I December 8, 2014 I Generon (Shanghai) Corporation, a leading biopharmaceutical company in China, today announced the presentation of the global Phase II study results for F-627 (benegrastim) at the American Society of Hematology (ASH®) 56th Annual Meeting at San Francisco entitled “Phase II, Randomized, Multi-Center, Open-Label, Active Controlled, Dose Finding Trial of F-627 (benegrastim) in Women with Breast Cancer Receiving Mylotoxic Chemotherapy” (poster #1584). Benegrastim demonstrated non-inferiority for the duration of moderate and severe neutropenia as compared to pegfilgrastim (Neulasta®) in patients with Stage I-IV breast cancer who received docetaxel / cyclophosphamide (TC) or Doxorubicin / docetaxel / cyclophosphamide (TAC) chemotherapy.
In the Phase II trial, 232 breast cancer patients were enrolled in 35 centers in the US and Eastern Europe. Each patient was scheduled to undergo four (21-day) chemotherapy cycles. Patients were randomized to receive F-627 or pegfilgrastim (6 mg fixed dose) one day after receiving their chemotherapy, for each cycle, as a subcutaneous injection. Three dose levels of F-627 (80, 240, and 320 μg/kg) vs. pegfilgrastim were tested in patients receiving the TC regimen, with a randomization ratio of 1:1:1:1. Two dose levels of F-627 (240 and 320 μg/kg) vs. pegfilgrastim were tested in patients receiving the TAC regimen, with a randomization ratio of 1:1:1. In this study, 141 patients received TC chemotherapy and 91 patients received TAC chemotherapy.
The primary efficacy endpoint of this study was the duration of grade 3 (moderate) and grade 4 (severe) neutropenia, defined as an ANC < 1.0 × 109/L, during the first cycle of chemotherapy. Secondary endpoints included the duration of grade 4 (severe) neutropenia, defined as an ANC < 0.5 × 109/L, for each chemotherapy cycle, evaluation of nadir depth for each chemotherapy cycle, the incidence rate of febrile neutropenia, and time to ANC recovery, defined as an ANC ≥ 2.0 × 109/L post nadir, for each chemotherapy cycle. For patients receiving the TC chemotherapy regimen, the mean difference in the duration of moderate and severe neutropenia in the Intent to Treat Population (ITT) for patients receiving benegrastim as compared to pegfilgrastim was 0.4 days for the 80 μg/kg group with a 95% CI (-0.1, 0.9), 0.3 days for the 240 μg/kg group with a 95% CI (-0.2, 0.8) and 0.3 days for the 320 μg/kg group with a 95% CI (-0.2, 0.9). For patients receiving the TAC chemotherapy regimen, the mean difference in the duration of moderate and severe neutropenia in the ITT for patients receiving benegrastim as compared to pegfilgrastim was 0.3 days for the 240 μg/kg group with a 95% CI (-0.5, 1.1) and 0.4 days for the 320 μg/kg group with a 95% CI (-0.4, 1.2). The secondary objective results for the 240 and 320 μg/kg benegrastim doses were also comparable to pegfilgrastim. The pre-specified non-inferiority margin of 2 days was met from all benegrastim doses in both TC and TAC groups, and was consistent from analysis of the ITT as well as the Per-protocol (PP) analysis populations.
The safety profiles of all doses of benegrastim were similar to that of pegfilgrastim. Two cases of febrile neutropenia were reported in the 320 μg/kg group and 2 cases were reported in the pegfilgrastim group. Three serious adverse events (SAEs) were reported from the combined benegrastim groups, 7 SAEs were reported from the pegfilgrastim group. Adverse events (AEs) coded under Infections and Infestations were reported for 8.6, 4.5 and 3.1% of the patients from the 80, 240, and 320 μg/kg benegrastim dose groups, respectively. Comparably, 9.2% of the patients from the pegfilgrastim group reported AEs coded under Infections and Infestations. No deaths were reported in this study.
Dr. J. Glaspy at UCLA Medical Center congratulated the Generon team and commented: “F-627 is a promising alternative treatment for chemo-induced neutropenia patients. The study was well conducted for a study this size to show non-inferiority.”
Dr. David Lacey, Chairman of the Scientific Advisory Board of Generon, also commented “The Ph II data for Generon’s F-627 that shows non-inferiority to the segment leader Neulasta (R) continues to support the promise of this novel, G-CSF-based therapeutic for use in settings where the risk of chemotherapy-induced febrile neutropenia is appreciable. This molecule presents G-CSF as a dimer and its prolonged half-life is in part due to recombinant fusion with human Fc. These data strongly support the continued development of F-627 for use in settings where myelotoxic therapies are deployed.”
Dr. Yuliang Huang, CEO of Generon said “We are extremely pleased about the exciting Phase II study results of benegrastim. This demonstrated our commitment of ‘innovating for life’ to bring innovative biologicals to patients in China and worldwide. Benegrastim allows us to compete in the approximately $7 billion global market.”
About Benegrastim
Benegrastim (F-627) is a rhG-CSF dimer (rhG-CSF-Fc fusion protein), a third generation recombinant human granulocyte colony-stimulating factor (G-CSF). Benegrastim is expressed as a dimer in mammalian cells. Benegrastim could potentially generate a quicker neutrophil recovery after chemotherapy and help physicians manage severe neutropenia.
About Generon (Shanghai) Corporation
Generon (Shanghai) Corporation (Generon) is a leading biopharmaceutical company located in China focusing on development of innovative biological therapies for global patients. For more information, please visit http://www.generonbiomed.com.
SOURCE: Generon
Post Views: 139
