Robust microdystrophin expression observed in new data from pivotal dose
Patients aged 5.8 and 8.5 years at dosing had expression levels at 77.2% and 46.5% of control, respectively
Consistent high expression of microdystrophin across treated patients in all age groups continues to support plans for accelerated approval
Expects to initiate pivotal trial in Q4 2024
ROCKVILLE, MD, USA I August 1, 2024 I REGENXBIO Inc. (Nasdaq: RGNX) today reported new, positive interim safety and efficacy data in the Phase I/II AFFINITY DUCHENNE® trial of RGX-202 in patients with Duchenne muscular dystrophy (Duchenne) ages 1 to 11 years old.
RGX-202 is an investigational one-time AAV Therapeutic designed to deliver a novel microdystrophin gene that includes key regions of the naturally occurring dystrophin gene. RGX-202 is the only gene therapy approved or in development for Duchenne that encodes for the C-Terminal (CT) domain to produce a microdystrophin that is closer to naturally occurring dystrophin. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself.
“With today’s new, positive data, we are seeing a clear dose response and consistent, robust microdystrophin expression levels across all treated patients in the AFFINITY DUCHENNE trial, and, notably, among the highest levels of microdystrophin expression reported in older ambulatory patients,” said Curran M. Simpson, President and CEO, REGENXBIO. “This data continues to build on the totality of evidence supporting the potential for RGX-202 to be a differentiated, best-in-class treatment for Duchenne. RGX-202 is well positioned to be the next potential gene therapy approved for Duchenne, and, with our commercial-ready, suspension-based manufacturing platform process, we believe we have the capacity to serve the entire market.”
“I remain encouraged by the biomarker data from the AFFINITY DUCHENNE trial of RGX-202 and am eagerly anticipating the initial functional data from this program,” said Aravindhan Veerapandiyan, M.D., Arkansas Children’s Hospital. “This update is also encouraging for the Duchenne community, which is exploring various treatment options that could influence disease progression.”
Data Update In patients aged 5.8 and 8.5 who received RGX-202 at dose level 2, RGX-202 microdystrophin expression was measured to be 77.2%, and 46.5%, respectively, compared to control at three months.
As of July 8, 2024, RGX-202 has been well tolerated with no serious adverse events. All seven patients who completed three-month trial assessments indicate meaningful increases in expression of RGX-202 microdystrophin and reduction from baseline in serum creatinine kinase levels, supporting evidence of clinical improvement.
Microdystrophin expression results to date by dose and age in the AFFINITY DUCHENNE trial are shown in the table below.
Clinical Program Updates RGX-202 in the AFFINITY DUCHENNE trial is manufactured at the REGENXBIO Manufacturing Innovation Center using the Company’s proprietary, high-yielding NAVXpress™ platform process. This suspension-based manufacturing process has demonstrated scalability up to 2,000L with consistent yield and product purity and is suitable for product commercialization. The REGENXBIO Manufacturing Innovation Center has the capacity and yields to produce up to 2,500 doses of RGX-202 per year.
REGENXBIO expects to complete enrollment in the dose level 2 expansion cohort early in the third quarter of 2024 and has initiated enrollment in the cohort for boys aged 1-3. Initiation of the pivotal trial is expected in the fourth quarter of 2024.
REGENXBIO expects to share initial strength and functional assessment data for both dose levels of the AFFINITY DUCHENNE trial in the second half of 2024.
AFFINITY DUCHENNE Trial Design The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne aged 1-11.
The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests.
About RGX-202 RGX-202 is a next-generation investigational gene therapy designed for improved function and outcomes in Duchenne. RGX-202 is the only gene therapy approved or in late-stage development for Duchenne with a differentiated microdystrophin construct that encodes key regions of naturally occurring dystrophin, including the C-Terminal (CT) domain. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase protein translation efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV® AAV8 vector and a well-characterized muscle-specific promoter (Spc5-12). RGX-202 is manufactured using REGENXBIO’s proprietary, high-yielding NAVXpress™ suspension-based platform process.
About Duchenne Muscular Dystrophy Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.
ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO’s AAV Therapeutic platform, including Novartis’ ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit www.regenxbio.com.
Robust microdystrophin expression observed in new data from pivotal dose
Patients aged 5.8 and 8.5 years at dosing had expression levels at 77.2% and 46.5% of control, respectively
Consistent high expression of microdystrophin across treated patients in all age groups continues to support plans for accelerated approval
Expects to initiate pivotal trial in Q4 2024
ROCKVILLE, MD, USA I August 1, 2024 I REGENXBIO Inc. (Nasdaq: RGNX) today reported new, positive interim safety and efficacy data in the Phase I/II AFFINITY DUCHENNE® trial of RGX-202 in patients with Duchenne muscular dystrophy (Duchenne) ages 1 to 11 years old.
RGX-202 is an investigational one-time AAV Therapeutic designed to deliver a novel microdystrophin gene that includes key regions of the naturally occurring dystrophin gene. RGX-202 is the only gene therapy approved or in development for Duchenne that encodes for the C-Terminal (CT) domain to produce a microdystrophin that is closer to naturally occurring dystrophin. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself.
“With today’s new, positive data, we are seeing a clear dose response and consistent, robust microdystrophin expression levels across all treated patients in the AFFINITY DUCHENNE trial, and, notably, among the highest levels of microdystrophin expression reported in older ambulatory patients,” said Curran M. Simpson, President and CEO, REGENXBIO. “This data continues to build on the totality of evidence supporting the potential for RGX-202 to be a differentiated, best-in-class treatment for Duchenne. RGX-202 is well positioned to be the next potential gene therapy approved for Duchenne, and, with our commercial-ready, suspension-based manufacturing platform process, we believe we have the capacity to serve the entire market.”
“I remain encouraged by the biomarker data from the AFFINITY DUCHENNE trial of RGX-202 and am eagerly anticipating the initial functional data from this program,” said Aravindhan Veerapandiyan, M.D., Arkansas Children’s Hospital. “This update is also encouraging for the Duchenne community, which is exploring various treatment options that could influence disease progression.”
Data Update In patients aged 5.8 and 8.5 who received RGX-202 at dose level 2, RGX-202 microdystrophin expression was measured to be 77.2%, and 46.5%, respectively, compared to control at three months.
As of July 8, 2024, RGX-202 has been well tolerated with no serious adverse events. All seven patients who completed three-month trial assessments indicate meaningful increases in expression of RGX-202 microdystrophin and reduction from baseline in serum creatinine kinase levels, supporting evidence of clinical improvement.
Microdystrophin expression results to date by dose and age in the AFFINITY DUCHENNE trial are shown in the table below.
Clinical Program Updates RGX-202 in the AFFINITY DUCHENNE trial is manufactured at the REGENXBIO Manufacturing Innovation Center using the Company’s proprietary, high-yielding NAVXpress™ platform process. This suspension-based manufacturing process has demonstrated scalability up to 2,000L with consistent yield and product purity and is suitable for product commercialization. The REGENXBIO Manufacturing Innovation Center has the capacity and yields to produce up to 2,500 doses of RGX-202 per year.
REGENXBIO expects to complete enrollment in the dose level 2 expansion cohort early in the third quarter of 2024 and has initiated enrollment in the cohort for boys aged 1-3. Initiation of the pivotal trial is expected in the fourth quarter of 2024.
REGENXBIO expects to share initial strength and functional assessment data for both dose levels of the AFFINITY DUCHENNE trial in the second half of 2024.
AFFINITY DUCHENNE Trial Design The Phase I/II AFFINITY DUCHENNE trial is a multicenter, open-label dose escalation and dose expansion clinical study to evaluate the safety, tolerability and clinical efficacy of a one-time intravenous (IV) dose of RGX-202 in patients with Duchenne aged 1-11.
The trial design was informed by the Duchenne community and engagement with key opinion leaders, including a comprehensive, short-term, prophylactic immunosuppression regimen to proactively mitigate potential complement-mediated immunologic responses, and inclusion criteria based on dystrophin gene mutation status, including DMD gene mutations in exons 18 and above. Trial endpoints include safety, immunogenicity assessments, pharmacodynamic and pharmacokinetic measures of RGX-202, including microdystrophin protein levels in muscle, and strength and functional assessments, including the North Star Ambulatory Assessment (NSAA) and timed function tests.
About RGX-202 RGX-202 is a next-generation investigational gene therapy designed for improved function and outcomes in Duchenne. RGX-202 is the only gene therapy approved or in late-stage development for Duchenne with a differentiated microdystrophin construct that encodes key regions of naturally occurring dystrophin, including the C-Terminal (CT) domain. In preclinical studies, the CT domain has been shown to protect the muscle from contraction-induced stress and improve its ability to repair itself. Additional design features, including codon optimization and reduction of CpG content, may potentially improve gene expression, increase protein translation efficiency and reduce immunogenicity. RGX-202 is designed to support the delivery and targeted expression of genes throughout skeletal and heart muscle using the NAV® AAV8 vector and a well-characterized muscle-specific promoter (Spc5-12). RGX-202 is manufactured using REGENXBIO’s proprietary, high-yielding NAVXpress™ suspension-based platform process.
About Duchenne Muscular Dystrophy Duchenne is a severe, progressive, degenerative muscle disease, affecting 1 in 3,500 to 5,000 boys born each year worldwide. Duchenne is caused by mutations in the Duchenne gene which encodes for dystrophin, a protein involved in muscle cell structure and signaling pathways. Without dystrophin, muscles throughout the body degenerate and become weak, eventually leading to loss of movement and independence, required support for breathing, cardiomyopathy and premature death.
ABOUT REGENXBIO Inc. REGENXBIO is a leading clinical-stage biotechnology company seeking to improve lives through the curative potential of gene therapy. Since its founding in 2009, REGENXBIO has pioneered the development of AAV Therapeutics, an innovative class of gene therapy medicines. REGENXBIO is advancing a pipeline of AAV Therapeutics for retinal and rare diseases, including ABBV-RGX-314 for the treatment of wet AMD and diabetic retinopathy, being developed in collaboration with AbbVie, RGX-202 for the treatment of Duchenne and RGX-121 for the treatment of MPS II. Thousands of patients have been treated with REGENXBIO’s AAV Therapeutic platform, including Novartis’ ZOLGENSMA for children with spinal muscular atrophy. Designed to be one-time treatments, AAV Therapeutics have the potential to change the way healthcare is delivered for millions of people. For more information, please visit www.regenxbio.com.
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