— Continued functional improvements were observed at 18 months in the low-dose cohort —
— First look at functional outcomes in high-dose cohort found improvements 6 months after administration —
— Results in both cohorts continue to reinforce safety and tolerability profile of SRP-9003 —
CAMBRIDGE, MA, USA I September 28, 2020 I Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced positive results from the ongoing study of SRP-9003 (rAAVrh74.MHCK7.hSGCB), the Company’s investigational gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E). Results included 18-month functional data from three clinical trial participants in the low-dose cohort and 6-month functional data from three participants in the high-dose cohort. SRP-9003 is in development for the treatment of LGMD2E (also known as beta-sarcoglycanopathy and LGMDR4), a devastating monogenic neuromuscular disease caused by a lack of beta-sarcoglycan proteins. SRP-9003 is a gene construct that transduces skeletal and cardiac muscle, delivering a gene that codes for the full-length beta-sarcoglycan protein, the absence of which is the sole cause of the progressive degeneration and a shortened lifespan characterized by the disease.
“There are currently no approved treatments for people with LGMD2E – a disease that causes significant disability in children and often leads to early mortality. It’s very encouraging that we continue to see consistent, positive data from our investigational gene therapy SRP-9003 across several measures, as we know the community needs more options,” said Louise Rodino-Klapac, Ph.D., senior vice president of gene therapy, Sarepta Therapeutics. “The improvements in functional measures at 18- and 6- months in participants from both cohorts who received SRP-9003 are distinctly different from what an age-matched, natural history group would predict with LGMD2E. This sustained durability of the response in functional outcomes reinforces that SRP-9003 is getting to the muscle and suggestive of improvement against disease-mediated muscle damage. When coupled with the strong expression results and encouraging safety profile seen to date, today’s results increase our confidence in the construct and provide additional evidence as we advance the higher dose of SRP-9003 into the next stage of clinical testing.”
Efficient transduction in skeletal muscle and robust beta-sarcoglycan protein expression were seen in both dose cohorts following infusion with SRP-9003, and significant creatine kinase (CK) reductions were observed at 90 days. Cohort-specific results as follows:
Cohort 1 (low dose), at 18 months:
- All three participants continued to show improvements from baseline across all functional measures, including the North Star Assessment for Dysferlinopathies (NSAD), time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test.
- The mean NSAD improvement from baseline was 3.0 at 6 months and 5.7 at 18 months.
- There have been no new drug-related safety signals observed since the one-year update in June 2020, and no decreases in platelet counts outside of the normal range or signs of complement activation were observed.
Cohort 2 (high dose), at 6 months:
- All three participants demonstrated improvements from baseline across all functional measures, including the NSAD, time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test.
- The mean NSAD improvement from baseline was 3.7.
- There have been no new drug-related safety signals observed since expression results were shared in June 2020, and no decreases in platelet counts outside of the normal range or signs of complement activation were observed.
About SRP-9003 and the study
SRP-9003 uses the AAVrh74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle, making it an ideal candidate to treat peripheral neuromuscular diseases. AAVrh74 has lower immunogenicity rates than reported with other human AAV vectors. The MHCK7 promoter has been chosen for its ability to robustly express in the heart, which is critically important for patients with limb-girdle muscular dystrophy Type 2E (LGMD2E), also known as beta-sarcoglycanopathy and LGMDR4, many of whom die from pulmonary or cardiac complications.
This first-in-human study is evaluating a single intravenous infusion of SRP-9003 among children with LGMD2E between the ages of 4 and 15 years with significant symptoms of disease. The SRP-9003 study has two cohorts, each studying a different dose-per-kilogram based on the weight of the patient. Three participants in the low-dose cohort (Cohort 1) were treated with a one-time infusion of SRP-9003 dosed at 5×1013 vg/kg and an additional three participants in the high-dose cohort (Cohort 2) received a one-time infusion dosed at 2×1014 vg/kg. The six participants were between the ages of 4 and 13. Post-treatment biopsies were taken at 60 days.
Sarepta has exclusive rights to the LGMD2E gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital.
About Limb-Girdle Muscular Dystrophy
Limb-girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begin in muscles around the hips and shoulders before progressing to muscles in the arms and legs.
Patients with limb-girdle muscular dystrophy Type 2E (LGMD2E) begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease, which is an autosomal recessive subtype of LGMD, progresses to loss of ambulation in the teen years and often leads to early mortality. There is currently no treatment or cure for LGMD2E.
Sarepta has five LGMD gene therapy programs in development, including subtypes for LGMD2E, LGMD2D, LGMD2C, LGMD2B and LGMD2L, and holds an option for a sixth program for LGMD2A.
About Sarepta Therapeutics
At Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Company’s programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visit www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.
SOURCE: Sarepta Therapeutics
Post Views: 546
— Continued functional improvements were observed at 18 months in the low-dose cohort —
— First look at functional outcomes in high-dose cohort found improvements 6 months after administration —
— Results in both cohorts continue to reinforce safety and tolerability profile of SRP-9003 —
CAMBRIDGE, MA, USA I September 28, 2020 I Sarepta Therapeutics, Inc. (NASDAQ:SRPT), the leader in precision genetic medicine for rare diseases, today announced positive results from the ongoing study of SRP-9003 (rAAVrh74.MHCK7.hSGCB), the Company’s investigational gene therapy for limb-girdle muscular dystrophy Type 2E (LGMD2E). Results included 18-month functional data from three clinical trial participants in the low-dose cohort and 6-month functional data from three participants in the high-dose cohort. SRP-9003 is in development for the treatment of LGMD2E (also known as beta-sarcoglycanopathy and LGMDR4), a devastating monogenic neuromuscular disease caused by a lack of beta-sarcoglycan proteins. SRP-9003 is a gene construct that transduces skeletal and cardiac muscle, delivering a gene that codes for the full-length beta-sarcoglycan protein, the absence of which is the sole cause of the progressive degeneration and a shortened lifespan characterized by the disease.
“There are currently no approved treatments for people with LGMD2E – a disease that causes significant disability in children and often leads to early mortality. It’s very encouraging that we continue to see consistent, positive data from our investigational gene therapy SRP-9003 across several measures, as we know the community needs more options,” said Louise Rodino-Klapac, Ph.D., senior vice president of gene therapy, Sarepta Therapeutics. “The improvements in functional measures at 18- and 6- months in participants from both cohorts who received SRP-9003 are distinctly different from what an age-matched, natural history group would predict with LGMD2E. This sustained durability of the response in functional outcomes reinforces that SRP-9003 is getting to the muscle and suggestive of improvement against disease-mediated muscle damage. When coupled with the strong expression results and encouraging safety profile seen to date, today’s results increase our confidence in the construct and provide additional evidence as we advance the higher dose of SRP-9003 into the next stage of clinical testing.”
Efficient transduction in skeletal muscle and robust beta-sarcoglycan protein expression were seen in both dose cohorts following infusion with SRP-9003, and significant creatine kinase (CK) reductions were observed at 90 days. Cohort-specific results as follows:
Cohort 1 (low dose), at 18 months:
- All three participants continued to show improvements from baseline across all functional measures, including the North Star Assessment for Dysferlinopathies (NSAD), time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test.
- The mean NSAD improvement from baseline was 3.0 at 6 months and 5.7 at 18 months.
- There have been no new drug-related safety signals observed since the one-year update in June 2020, and no decreases in platelet counts outside of the normal range or signs of complement activation were observed.
Cohort 2 (high dose), at 6 months:
- All three participants demonstrated improvements from baseline across all functional measures, including the NSAD, time-to-rise, four-stair climb, 100-meter walk test and 10-meter walk test.
- The mean NSAD improvement from baseline was 3.7.
- There have been no new drug-related safety signals observed since expression results were shared in June 2020, and no decreases in platelet counts outside of the normal range or signs of complement activation were observed.
About SRP-9003 and the study
SRP-9003 uses the AAVrh74 vector, which is designed to be systemically and robustly delivered to skeletal, diaphragm and cardiac muscle, making it an ideal candidate to treat peripheral neuromuscular diseases. AAVrh74 has lower immunogenicity rates than reported with other human AAV vectors. The MHCK7 promoter has been chosen for its ability to robustly express in the heart, which is critically important for patients with limb-girdle muscular dystrophy Type 2E (LGMD2E), also known as beta-sarcoglycanopathy and LGMDR4, many of whom die from pulmonary or cardiac complications.
This first-in-human study is evaluating a single intravenous infusion of SRP-9003 among children with LGMD2E between the ages of 4 and 15 years with significant symptoms of disease. The SRP-9003 study has two cohorts, each studying a different dose-per-kilogram based on the weight of the patient. Three participants in the low-dose cohort (Cohort 1) were treated with a one-time infusion of SRP-9003 dosed at 5×1013 vg/kg and an additional three participants in the high-dose cohort (Cohort 2) received a one-time infusion dosed at 2×1014 vg/kg. The six participants were between the ages of 4 and 13. Post-treatment biopsies were taken at 60 days.
Sarepta has exclusive rights to the LGMD2E gene therapy program initially developed at the Abigail Wexner Research Institute at Nationwide Children’s Hospital.
About Limb-Girdle Muscular Dystrophy
Limb-girdle muscular dystrophies are genetic diseases that cause progressive, debilitating weakness and wasting that begin in muscles around the hips and shoulders before progressing to muscles in the arms and legs.
Patients with limb-girdle muscular dystrophy Type 2E (LGMD2E) begin showing neuromuscular symptoms such as difficulty running, jumping and climbing stairs before age 10. The disease, which is an autosomal recessive subtype of LGMD, progresses to loss of ambulation in the teen years and often leads to early mortality. There is currently no treatment or cure for LGMD2E.
Sarepta has five LGMD gene therapy programs in development, including subtypes for LGMD2E, LGMD2D, LGMD2C, LGMD2B and LGMD2L, and holds an option for a sixth program for LGMD2A.
About Sarepta Therapeutics
At Sarepta, we are leading a revolution in precision genetic medicine and every day is an opportunity to change the lives of people living with rare disease. The Company has built an impressive position in Duchenne muscular dystrophy (DMD) and in gene therapies for limb-girdle muscular dystrophies (LGMDs), mucopolysaccharidosis type IIIA, Charcot-Marie-Tooth (CMT), and other CNS-related disorders, with more than 40 programs in various stages of development. The Company’s programs and research focus span several therapeutic modalities, including RNA, gene therapy and gene editing. For more information, please visit www.sarepta.com or follow us on Twitter, LinkedIn, Instagram and Facebook.
SOURCE: Sarepta Therapeutics
Post Views: 546
