On December 11, 2017 Italfarmaco Group, a specialty pharmaceutical company, reported the positive results from two clinical trials evaluating its proprietary histone deacetylase (HDAC) inhibitor givinostat in Polycythemia Vera patients -Italfarmaco Group, a specialty pharmaceutical company, reported the positive results from two clinical trials evaluating its proprietary histone deacetylase (HDAC) inhibitor givinostat in Polycythemia Vera patients. The data were presented in an oral and a poster presentation on Saturday December 9th, 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition held in Atlanta, Georgia. In the oral presentation, the company discussed positive safety and efficacy data from a two-part study of givinostat in which over 80% of patients responded to the treatment. These results were further supported by a poster presentation of a long-term evaluation of givinostat’s effect in patients over four years. Combined, the data provide a basis for the company’s decision to proceed with a pivotal Phase III trial in this indication. Polycythemia Vera is a rare blood disease characterized by an increased number of red blood cells, white blood cells and platelets, which significantly raises the risk for thromboembolic and hemorrhagic complications.

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"Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."
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In the oral presentation at ASH (Free ASH Whitepaper), the principal investigator described the multi-center, open label Phase Ib/II givinostat study, which included a dose-escalation and an evaluation of preliminary efficacy and tolerability. The data demonstrated that givinostat was well tolerated overall at the defined dose of 100 mg twice daily and the majority of adverse events were mild to moderate in severity. The overall response rate was more than 80% according to European Leukemia Net standard response criteria, which measure a range of parameters including reduction of the size of spleen and liver, peripheral blood count, absence of hemorrhagic and thrombotic events and bone marrow analysis.

In the larger study investigating long-term safety and efficacy, Italfarmaco researchers and collaborators presented data supporting the potential of givinostat as a durable treatment option that reduces the symptoms and underlying risks of the disease while remaining well-tolerated. Overall, 80% of patients maintained at least a partial response for more than four years. After four years of treatment no patient reported microvascular symptoms or headaches. Pruritus (itchiness), one of the typical symptoms of Polycythemia Vera, was absent in 67% of the patients. Furthermore, the overall incidence of thrombosis (1.13% patients per year) was reduced in comparison to the expected incidence rate in this patient population (3% patients/year). Givinostat treatment additionally reduced the levels of mutated Janus Kinase 2 (JAK2), a key underlying cause of the disease, by 25% in over 40% of the patients.

"The givinostat Phase II proof-of-concept and long-term data are very encouraging and demonstrate the potential of this compound to address the underlying mechanism of the disease while remaining well-tolerated," said Dr. Paolo Bettica, Vice President Research and Development. "Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."

"Italfarmaco is particularly gratified that these results were selected for presentation at ASH (Free ASH Whitepaper) because they underscore the value of our internal research and development efforts," added Dr. Francesco De Santis, President of Italfarmaco.

About Polycythemia Vera

Polycythemia Vera is a rare blood disease characterized by an overproduction of red blood cells, white blood cells and platelets, which thickens the blood and increases the risk of blood clots, a major underlying cause of life-threatening conditions such as thrombosis, embolisms, heart attack or stroke. The disease is associated with mutations in the Janus Kinase 2 (JAK2) gene and disease-related symptoms include headaches, itching and microvascular symptoms. The current standard of care ranges from phlebotomy alone or in combination with low-dose aspirin, to drugs such as the cytoreductive hydroxycarbamide or the JAK inhibitor ruxolitinib. These reduce symptoms, but no treatments targeting the underlying disease mechanism are available.

About Givinostat

Givinostat is a potent, orally-available, class I and II histone deacetylase (HDAC) inhibitor and an investigational product discovered through Italfarmaco’s internal research and development efforts. Through the pharmacological modulation of cell growth, differentiation and apoptosis and the additional specific inhibition of the proliferation of cells bearing the JAK2V617F mutation, givinostat may represent a novel disease modifier in Polycythemia Vera. Besides these properties, givinostat has shown immuno-modulatory activity that may specifically target other diseases, making it a very promising candidate for Duchenne Muscular Dystrophy (Phase III) and Becker Muscular Dystrophy (Phase II). The data were presented in an oral and a poster presentation on Saturday December 9th, 2017 at the 59th American Society of Hematology (ASH) (Free ASH Whitepaper) Meeting & Exposition held in Atlanta, Georgia. In the oral presentation, the company discussed positive safety and efficacy data from a two-part study of givinostat in which over 80% of patients responded to the treatment. These results were further supported by a poster presentation of a long-term evaluation of givinostat’s effect in patients over four years. Combined, the data provide a basis for the company’s decision to proceed with a pivotal Phase III trial in this indication. Polycythemia Vera is a rare blood disease characterized by an increased number of red blood cells, white blood cells and platelets, which significantly raises the risk for thromboembolic and hemorrhagic complications.

"Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."
Tweet this
In the oral presentation at ASH (Free ASH Whitepaper), the principal investigator described the multi-center, open label Phase Ib/II givinostat study, which included a dose-escalation and an evaluation of preliminary efficacy and tolerability. The data demonstrated that givinostat was well tolerated overall at the defined dose of 100 mg twice daily and the majority of adverse events were mild to moderate in severity. The overall response rate was more than 80% according to European Leukemia Net standard response criteria, which measure a range of parameters including reduction of the size of spleen and liver, peripheral blood count, absence of hemorrhagic and thrombotic events and bone marrow analysis.

In the larger study investigating long-term safety and efficacy, Italfarmaco researchers and collaborators presented data supporting the potential of givinostat as a durable treatment option that reduces the symptoms and underlying risks of the disease while remaining well-tolerated. Overall, 80% of patients maintained at least a partial response for more than four years. After four years of treatment no patient reported microvascular symptoms or headaches. Pruritus (itchiness), one of the typical symptoms of Polycythemia Vera, was absent in 67% of the patients. Furthermore, the overall incidence of thrombosis (1.13% patients per year) was reduced in comparison to the expected incidence rate in this patient population (3% patients/year). Givinostat treatment additionally reduced the levels of mutated Janus Kinase 2 (JAK2), a key underlying cause of the disease, by 25% in over 40% of the patients.

"The givinostat Phase II proof-of-concept and long-term data are very encouraging and demonstrate the potential of this compound to address the underlying mechanism of the disease while remaining well-tolerated," said Dr. Paolo Bettica, Vice President Research and Development. "Polycythemia Vera patients have limited treatment options that currently only ameliorate the symptoms of the disease. We look forward to initiating the planned pivotal study in this indication."

"Italfarmaco is particularly gratified that these results were selected for presentation at ASH (Free ASH Whitepaper) because they underscore the value of our internal research and development efforts," added Dr. Francesco De Santis, President of Italfarmaco.

About Polycythemia Vera

Polycythemia Vera is a rare blood disease characterized by an overproduction of red blood cells, white blood cells and platelets, which thickens the blood and increases the risk of blood clots, a major underlying cause of life-threatening conditions such as thrombosis, embolisms, heart attack or stroke. The disease is associated with mutations in the Janus Kinase 2 (JAK2) gene and disease-related symptoms include headaches, itching and microvascular symptoms. The current standard of care ranges from phlebotomy alone or in combination with low-dose aspirin, to drugs such as the cytoreductive hydroxycarbamide or the JAK inhibitor ruxolitinib. These reduce symptoms, but no treatments targeting the underlying disease mechanism are available.

About Givinostat

Givinostat is a potent, orally-available, class I and II histone deacetylase (HDAC) inhibitor and an investigational product discovered through Italfarmaco’s internal research and development efforts. Through the pharmacological modulation of cell growth, differentiation and apoptosis and the additional specific inhibition of the proliferation of cells bearing the JAK2V617F mutation, givinostat may represent a novel disease modifier in Polycythemia Vera. Besides these properties, givinostat has shown immuno-modulatory activity that may specifically target other diseases, making it a very promising candidate for Duchenne Muscular Dystrophy (Phase III) and Becker Muscular Dystrophy (Phase II).