PHASE 1 SUMMARY OF ANF-RHO, A NOVEL PEG-MODIFIED FILGRASTIM INVESTIGATIONAL PRODUCT WITH SUPERIOR PK/PD PROPERTIES THAT MAY PROVIDE IMPROVED CONTROL OF NEUTROPENIA DURING DOSE-DENSE CHEMOTHERAPY
(Abstract release date: 05/19/16)
EHA Library. Jubin R. 06/09/16; 132724; E1175
Disclosure(s): Ron Jubin is an employee of Prolong Pharmaceuticals.
Dr. Ronald Jubin
Contributions
Contributions
Abstract
Abstract: E1175
Type: Eposter Presentation
Background
Anti-Neutropenia Factor - Rho (ANF-RHO) is a new longer acting granulocyte-colony stimulating factor (G-CSF) consisting of a novel pegylated version of recombinant human G-CSF protein. ANF-RHO has distinct biophysical and biological properties that produce an improved pharmacokinetic (PK) and pharmacodynamic (PD) profile as compared to either filgrastim (Neupogen®) or PEGfilgrastim (Neulasta®). ANF-RHO is not a biosimilar drug product.
Aims
A Phase 1 clinical study was conducted in healthy volunteers to assess safety and tolerability of ANF-RHO as well as its PK and PD profile.
Methods
The ANF-RHO cohort dosage levels ranged from 5 to50 μg/kg and were compared against both active (PEGfilgrastim) and placebo (saline) comparators. Subcutaneous, single dose treatment with ANF-RHO in ascending doses or PEGfilgrastim at the standard of care dosage (fixed, 6mg) were compared in a randomized, controlled, double-blind study that included peripheral blood absolute neutrophil counts (ANC) and CD34+ stem cell analytical assessments.
Results
Phase 1 clinical safety results were unremarkable, with no severe adverse events in any cohorts. The ANF-RHO PK/PD results in this Phase 1 study were similar to preclinical findings. PK and PD results (ANC and CD34+) were markedly prolonged in the ANF-RHO treatment groups even at the lowest dose. Mean ANC counts for all ANF-RHO treated subjects showed Cmax at 6-7 days, in contrast to 1-2 days for PEGfilgrastim treated subjects. The peak blood levels of ANF-RHO were significantly lower than PEGfilgrastim at all levels tested. Moreover, assessment of the ANC - AUC revealed that ANF-RHO at10 μg/kg was equivalent to PEGfilgrastim at 100 μg/kg, demonstrating an approximately 10-fold potency improvement over PEGfilgrastim in healthy volunteers, with a longer duration of effect of almost two weeks. Peripheral blood CD34+ levels also yielded similar results. ANF-RHO-induced neutrophil counts increased in a stable and prolonged manner following treatment, followed by a slow gradual decline, in contrast to PEGfilgrastim that showed a rapid ANC spike (2 days) and decrease to baseline within 7 days following administration.
Conclusion
The unique PK/PD of ANF-RHO suggests that a significantly lower dosage may achieve sustained neutrophil levels sufficient to mitigate neutropenia - specifically during the high-risk 7-day period following dose-dense myelosuppressive chemotherapy. Additionally, the sustained and elevated CD34+ counts suggest ANF-RHO may also have applications in stem cell mobilization. The lower effective dosages would be anticipated to reduce the incidence of leukocytosis. Collectively, the increased potency and prolonged pharmacodynamics of ANF-RHO should provide more effective management of hematological malignancies when treating patients at high risk for neutropenia and difficult to mobilize patients or when performing dose-intensification in advanced stage cancer patients.
Session topic: E-poster
Keyword(s): Neutropenia, Pegfilgrastim, Pharmacokinetic, Supportive care
Type: Eposter Presentation
Background
Anti-Neutropenia Factor - Rho (ANF-RHO) is a new longer acting granulocyte-colony stimulating factor (G-CSF) consisting of a novel pegylated version of recombinant human G-CSF protein. ANF-RHO has distinct biophysical and biological properties that produce an improved pharmacokinetic (PK) and pharmacodynamic (PD) profile as compared to either filgrastim (Neupogen®) or PEGfilgrastim (Neulasta®). ANF-RHO is not a biosimilar drug product.
Aims
A Phase 1 clinical study was conducted in healthy volunteers to assess safety and tolerability of ANF-RHO as well as its PK and PD profile.
Methods
The ANF-RHO cohort dosage levels ranged from 5 to50 μg/kg and were compared against both active (PEGfilgrastim) and placebo (saline) comparators. Subcutaneous, single dose treatment with ANF-RHO in ascending doses or PEGfilgrastim at the standard of care dosage (fixed, 6mg) were compared in a randomized, controlled, double-blind study that included peripheral blood absolute neutrophil counts (ANC) and CD34+ stem cell analytical assessments.
Results
Phase 1 clinical safety results were unremarkable, with no severe adverse events in any cohorts. The ANF-RHO PK/PD results in this Phase 1 study were similar to preclinical findings. PK and PD results (ANC and CD34+) were markedly prolonged in the ANF-RHO treatment groups even at the lowest dose. Mean ANC counts for all ANF-RHO treated subjects showed Cmax at 6-7 days, in contrast to 1-2 days for PEGfilgrastim treated subjects. The peak blood levels of ANF-RHO were significantly lower than PEGfilgrastim at all levels tested. Moreover, assessment of the ANC - AUC revealed that ANF-RHO at10 μg/kg was equivalent to PEGfilgrastim at 100 μg/kg, demonstrating an approximately 10-fold potency improvement over PEGfilgrastim in healthy volunteers, with a longer duration of effect of almost two weeks. Peripheral blood CD34+ levels also yielded similar results. ANF-RHO-induced neutrophil counts increased in a stable and prolonged manner following treatment, followed by a slow gradual decline, in contrast to PEGfilgrastim that showed a rapid ANC spike (2 days) and decrease to baseline within 7 days following administration.
Conclusion
The unique PK/PD of ANF-RHO suggests that a significantly lower dosage may achieve sustained neutrophil levels sufficient to mitigate neutropenia - specifically during the high-risk 7-day period following dose-dense myelosuppressive chemotherapy. Additionally, the sustained and elevated CD34+ counts suggest ANF-RHO may also have applications in stem cell mobilization. The lower effective dosages would be anticipated to reduce the incidence of leukocytosis. Collectively, the increased potency and prolonged pharmacodynamics of ANF-RHO should provide more effective management of hematological malignancies when treating patients at high risk for neutropenia and difficult to mobilize patients or when performing dose-intensification in advanced stage cancer patients.
Session topic: E-poster
Keyword(s): Neutropenia, Pegfilgrastim, Pharmacokinetic, Supportive care
Abstract: E1175
Type: Eposter Presentation
Background
Anti-Neutropenia Factor - Rho (ANF-RHO) is a new longer acting granulocyte-colony stimulating factor (G-CSF) consisting of a novel pegylated version of recombinant human G-CSF protein. ANF-RHO has distinct biophysical and biological properties that produce an improved pharmacokinetic (PK) and pharmacodynamic (PD) profile as compared to either filgrastim (Neupogen®) or PEGfilgrastim (Neulasta®). ANF-RHO is not a biosimilar drug product.
Aims
A Phase 1 clinical study was conducted in healthy volunteers to assess safety and tolerability of ANF-RHO as well as its PK and PD profile.
Methods
The ANF-RHO cohort dosage levels ranged from 5 to50 μg/kg and were compared against both active (PEGfilgrastim) and placebo (saline) comparators. Subcutaneous, single dose treatment with ANF-RHO in ascending doses or PEGfilgrastim at the standard of care dosage (fixed, 6mg) were compared in a randomized, controlled, double-blind study that included peripheral blood absolute neutrophil counts (ANC) and CD34+ stem cell analytical assessments.
Results
Phase 1 clinical safety results were unremarkable, with no severe adverse events in any cohorts. The ANF-RHO PK/PD results in this Phase 1 study were similar to preclinical findings. PK and PD results (ANC and CD34+) were markedly prolonged in the ANF-RHO treatment groups even at the lowest dose. Mean ANC counts for all ANF-RHO treated subjects showed Cmax at 6-7 days, in contrast to 1-2 days for PEGfilgrastim treated subjects. The peak blood levels of ANF-RHO were significantly lower than PEGfilgrastim at all levels tested. Moreover, assessment of the ANC - AUC revealed that ANF-RHO at10 μg/kg was equivalent to PEGfilgrastim at 100 μg/kg, demonstrating an approximately 10-fold potency improvement over PEGfilgrastim in healthy volunteers, with a longer duration of effect of almost two weeks. Peripheral blood CD34+ levels also yielded similar results. ANF-RHO-induced neutrophil counts increased in a stable and prolonged manner following treatment, followed by a slow gradual decline, in contrast to PEGfilgrastim that showed a rapid ANC spike (2 days) and decrease to baseline within 7 days following administration.
Conclusion
The unique PK/PD of ANF-RHO suggests that a significantly lower dosage may achieve sustained neutrophil levels sufficient to mitigate neutropenia - specifically during the high-risk 7-day period following dose-dense myelosuppressive chemotherapy. Additionally, the sustained and elevated CD34+ counts suggest ANF-RHO may also have applications in stem cell mobilization. The lower effective dosages would be anticipated to reduce the incidence of leukocytosis. Collectively, the increased potency and prolonged pharmacodynamics of ANF-RHO should provide more effective management of hematological malignancies when treating patients at high risk for neutropenia and difficult to mobilize patients or when performing dose-intensification in advanced stage cancer patients.
Session topic: E-poster
Keyword(s): Neutropenia, Pegfilgrastim, Pharmacokinetic, Supportive care
Type: Eposter Presentation
Background
Anti-Neutropenia Factor - Rho (ANF-RHO) is a new longer acting granulocyte-colony stimulating factor (G-CSF) consisting of a novel pegylated version of recombinant human G-CSF protein. ANF-RHO has distinct biophysical and biological properties that produce an improved pharmacokinetic (PK) and pharmacodynamic (PD) profile as compared to either filgrastim (Neupogen®) or PEGfilgrastim (Neulasta®). ANF-RHO is not a biosimilar drug product.
Aims
A Phase 1 clinical study was conducted in healthy volunteers to assess safety and tolerability of ANF-RHO as well as its PK and PD profile.
Methods
The ANF-RHO cohort dosage levels ranged from 5 to50 μg/kg and were compared against both active (PEGfilgrastim) and placebo (saline) comparators. Subcutaneous, single dose treatment with ANF-RHO in ascending doses or PEGfilgrastim at the standard of care dosage (fixed, 6mg) were compared in a randomized, controlled, double-blind study that included peripheral blood absolute neutrophil counts (ANC) and CD34+ stem cell analytical assessments.
Results
Phase 1 clinical safety results were unremarkable, with no severe adverse events in any cohorts. The ANF-RHO PK/PD results in this Phase 1 study were similar to preclinical findings. PK and PD results (ANC and CD34+) were markedly prolonged in the ANF-RHO treatment groups even at the lowest dose. Mean ANC counts for all ANF-RHO treated subjects showed Cmax at 6-7 days, in contrast to 1-2 days for PEGfilgrastim treated subjects. The peak blood levels of ANF-RHO were significantly lower than PEGfilgrastim at all levels tested. Moreover, assessment of the ANC - AUC revealed that ANF-RHO at10 μg/kg was equivalent to PEGfilgrastim at 100 μg/kg, demonstrating an approximately 10-fold potency improvement over PEGfilgrastim in healthy volunteers, with a longer duration of effect of almost two weeks. Peripheral blood CD34+ levels also yielded similar results. ANF-RHO-induced neutrophil counts increased in a stable and prolonged manner following treatment, followed by a slow gradual decline, in contrast to PEGfilgrastim that showed a rapid ANC spike (2 days) and decrease to baseline within 7 days following administration.
Conclusion
The unique PK/PD of ANF-RHO suggests that a significantly lower dosage may achieve sustained neutrophil levels sufficient to mitigate neutropenia - specifically during the high-risk 7-day period following dose-dense myelosuppressive chemotherapy. Additionally, the sustained and elevated CD34+ counts suggest ANF-RHO may also have applications in stem cell mobilization. The lower effective dosages would be anticipated to reduce the incidence of leukocytosis. Collectively, the increased potency and prolonged pharmacodynamics of ANF-RHO should provide more effective management of hematological malignancies when treating patients at high risk for neutropenia and difficult to mobilize patients or when performing dose-intensification in advanced stage cancer patients.
Session topic: E-poster
Keyword(s): Neutropenia, Pegfilgrastim, Pharmacokinetic, Supportive care
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