Data from IND-enabling studies in three species support moving SPK-3006 into the clinic in 2019
PHILADELPHIA, PA, USA I October 08, 2018 I Spark Therapeutics (NASDAQ:ONCE), a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced new data for SPK-3006, an investigational liver-directed adeno-associated viral (AAV) gene therapy for Pompe disease. The data from the Investigational New Drug (IND)-enabling studies were presented Saturday, Oct. 6, 2018, in an oral presentation, “Safety and efficacy evaluation of investigational liver gene transfer for secretable GAA in the treatment of Pompe disease,” during the Late Breaking Session at the 23rd International Congress of the World Muscle Society in Argentina.
Pompe disease is a rare, inherited lysosomal storage disease. It is a progressive, often life-limiting disease caused by the buildup of a complex sugar, glycogen, in the body’s cells. Mutations in the gene encoding acid alpha-glucosidase (GAA) result in deficiencies of the enzyme GAA and limit the breakdown of glycogen. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function. The skeletal muscle cells (including those used in respiration) and heart cells are most affected by Pompe disease.
Unlike the current standard of care, enzyme replacement therapy (ERT), where patients receive recombinant GAA infusions every two weeks, Spark’s one-time investigational gene therapy, SPK-3006, has been engineered to produce a modified GAA enzyme that is secreted from the liver with high efficiency. This is hypothesized to lower immunogenicity to GAA and, in preclinical models, has been shown to sustain plasma levels of GAA to provide increased uptake in muscle tissue throughout the body and more efficiently break down glycogen.
Spark Therapeutics licensed the intellectual property for the transgene in SPK-3006 from Genethon in 2017. Preclinical studies in a Pompe disease model demonstrated a greater therapeutic response and a lower immunogenicity profile of secretable GAA expressed by this transgene in liver cells following AAV gene transfer compared to both native GAA expressed by the liver as well as native GAA expressed directly in muscle tissue.
Preclinical studies evaluating activity of the secretable, modified GAA enzyme found in SPK-3006 in acid alpha-glucosidase knockout (Gaa-/-) mice showed decreased glycogen accumulation, increased survival and improved cardiac, respiratory and muscle function. In these studies, animals were followed up for up to 10 months after gene transfer and no vector-related toxicities were observed. Importantly, the induced liver expression of secretable GAA demonstrated greater ability in restoring muscle strength compared to the standard of care regimen of 20 mg/kg bi-weekly ERT. Secretable GAA was significantly better than ERT in breaking down glycogen in refractory muscle groups, including quadriceps and triceps.
Additionally, a single infusion of SPK-3006 at three ascending doses in a non-human primate (NHP) study conducted by Spark Therapeutics demonstrated dose-dependent expression of GAA in plasma. Long-term follow up of NHPs following infusion of SPK-3006 is ongoing, with a six-month follow up to date and no observed vector-related toxicities.
“We are capitalizing on our proven and proprietary AAV gene therapy platform to target and use liver cells to consistently express GAA in the plasma of animals. Early preclinical data suggest sustained plasma levels of GAA facilitate greater uptake into muscle tissue throughout the body, efficient clearance of glycogen, as well as improved restoration of GAA muscle strength when compared to standard of care,” said Federico Mingozzi, Ph.D., chief scientific officer at Spark Therapeutics. “In these studies, expression of GAA from hepatocytes was considerably less immunogenic because of an induction of immunological tolerance mediated by the liver rather than the muscle. To date, IND-enabling preclinical studies support our approach, leading us to plan for the initiation of a Phase 1/2 clinical trial to assess the safety of this investigational gene therapy in 2019.”
Spark Therapeutics has conducted a pre-IND meeting regarding SPK-3006 with FDA. After completing an ongoing Good Laboratory Practice (GLP) toxicology and biodistribution study, Spark Therapeutics will submit an IND application and Clinical Trial Application (CTA) to regulatory agencies and initiate a U.S. and EU Phase 1/2 clinical trial of SPK-3006 in adult patients in 2019.
About SPK-3006 for Pompe disease
SPK-3006 is an investigational liver-directed AAV gene therapy for Pompe disease. SPK-3006 has been engineered to produce a modified enzyme that is secreted from the liver, which may sustain GAA plasma levels and lower immunogenicity to GAA to potentially provide greater uptake in muscle tissue. The transgene was in-licensed in 2017 from Genethon, a non-profit research and development organization dedicated to the development of gene therapies for orphan genetic diseases from research to clinical validation. Spark Therapeutics retains global commercialization rights to SPK-3006.
About Spark Therapeutics
At Spark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challenge the inevitability of genetic diseases, including blindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases. We have successfully applied our technology in the first FDA-approved gene therapy in the U.S. for a genetic disease, and currently have three programs in clinical trials, including product candidates that have shown promising early results in patients with hemophilia. At Spark, we see the path to a world where no life is limited by genetic disease. For more information, visit www.sparktx.com, and follow us on Twitter and LinkedIn.
SOURCE: Spark Therapeutics
Post Views: 564
Data from IND-enabling studies in three species support moving SPK-3006 into the clinic in 2019
PHILADELPHIA, PA, USA I October 08, 2018 I Spark Therapeutics (NASDAQ:ONCE), a fully integrated, commercial gene therapy company dedicated to challenging the inevitability of genetic disease, today announced new data for SPK-3006, an investigational liver-directed adeno-associated viral (AAV) gene therapy for Pompe disease. The data from the Investigational New Drug (IND)-enabling studies were presented Saturday, Oct. 6, 2018, in an oral presentation, “Safety and efficacy evaluation of investigational liver gene transfer for secretable GAA in the treatment of Pompe disease,” during the Late Breaking Session at the 23rd International Congress of the World Muscle Society in Argentina.
Pompe disease is a rare, inherited lysosomal storage disease. It is a progressive, often life-limiting disease caused by the buildup of a complex sugar, glycogen, in the body’s cells. Mutations in the gene encoding acid alpha-glucosidase (GAA) result in deficiencies of the enzyme GAA and limit the breakdown of glycogen. The accumulation of glycogen in certain organs and tissues, especially muscles, impairs their ability to function. The skeletal muscle cells (including those used in respiration) and heart cells are most affected by Pompe disease.
Unlike the current standard of care, enzyme replacement therapy (ERT), where patients receive recombinant GAA infusions every two weeks, Spark’s one-time investigational gene therapy, SPK-3006, has been engineered to produce a modified GAA enzyme that is secreted from the liver with high efficiency. This is hypothesized to lower immunogenicity to GAA and, in preclinical models, has been shown to sustain plasma levels of GAA to provide increased uptake in muscle tissue throughout the body and more efficiently break down glycogen.
Spark Therapeutics licensed the intellectual property for the transgene in SPK-3006 from Genethon in 2017. Preclinical studies in a Pompe disease model demonstrated a greater therapeutic response and a lower immunogenicity profile of secretable GAA expressed by this transgene in liver cells following AAV gene transfer compared to both native GAA expressed by the liver as well as native GAA expressed directly in muscle tissue.
Preclinical studies evaluating activity of the secretable, modified GAA enzyme found in SPK-3006 in acid alpha-glucosidase knockout (Gaa-/-) mice showed decreased glycogen accumulation, increased survival and improved cardiac, respiratory and muscle function. In these studies, animals were followed up for up to 10 months after gene transfer and no vector-related toxicities were observed. Importantly, the induced liver expression of secretable GAA demonstrated greater ability in restoring muscle strength compared to the standard of care regimen of 20 mg/kg bi-weekly ERT. Secretable GAA was significantly better than ERT in breaking down glycogen in refractory muscle groups, including quadriceps and triceps.
Additionally, a single infusion of SPK-3006 at three ascending doses in a non-human primate (NHP) study conducted by Spark Therapeutics demonstrated dose-dependent expression of GAA in plasma. Long-term follow up of NHPs following infusion of SPK-3006 is ongoing, with a six-month follow up to date and no observed vector-related toxicities.
“We are capitalizing on our proven and proprietary AAV gene therapy platform to target and use liver cells to consistently express GAA in the plasma of animals. Early preclinical data suggest sustained plasma levels of GAA facilitate greater uptake into muscle tissue throughout the body, efficient clearance of glycogen, as well as improved restoration of GAA muscle strength when compared to standard of care,” said Federico Mingozzi, Ph.D., chief scientific officer at Spark Therapeutics. “In these studies, expression of GAA from hepatocytes was considerably less immunogenic because of an induction of immunological tolerance mediated by the liver rather than the muscle. To date, IND-enabling preclinical studies support our approach, leading us to plan for the initiation of a Phase 1/2 clinical trial to assess the safety of this investigational gene therapy in 2019.”
Spark Therapeutics has conducted a pre-IND meeting regarding SPK-3006 with FDA. After completing an ongoing Good Laboratory Practice (GLP) toxicology and biodistribution study, Spark Therapeutics will submit an IND application and Clinical Trial Application (CTA) to regulatory agencies and initiate a U.S. and EU Phase 1/2 clinical trial of SPK-3006 in adult patients in 2019.
About SPK-3006 for Pompe disease
SPK-3006 is an investigational liver-directed AAV gene therapy for Pompe disease. SPK-3006 has been engineered to produce a modified enzyme that is secreted from the liver, which may sustain GAA plasma levels and lower immunogenicity to GAA to potentially provide greater uptake in muscle tissue. The transgene was in-licensed in 2017 from Genethon, a non-profit research and development organization dedicated to the development of gene therapies for orphan genetic diseases from research to clinical validation. Spark Therapeutics retains global commercialization rights to SPK-3006.
About Spark Therapeutics
At Spark Therapeutics, a fully integrated, commercial company committed to discovering, developing and delivering gene therapies, we challenge the inevitability of genetic diseases, including blindness, hemophilia, lysosomal storage disorders and neurodegenerative diseases. We have successfully applied our technology in the first FDA-approved gene therapy in the U.S. for a genetic disease, and currently have three programs in clinical trials, including product candidates that have shown promising early results in patients with hemophilia. At Spark, we see the path to a world where no life is limited by genetic disease. For more information, visit www.sparktx.com, and follow us on Twitter and LinkedIn.
SOURCE: Spark Therapeutics
Post Views: 564
