Retinal Dystrophy, Early Onset Severe

[01-November-2023] HG004 is the first China-developed AAV gene therapy medicine to be evaluated in a multinational, master-protocol clinical trial for patients with inherited retinal dystrophies caused by mutations in RPE65 gene HG004 is also first China independently-developed gene therapy drug granted both ODD and RPDD by the U.S. FDA HG004 is Company's first product candidate from robust pipeline of ophthalmology and neurology advances into the clinic SHANGHAI and CLINTON, N.J., Nov. 1, 2023 /PRNewswire/ -- HuidaGene Therapeutics (辉大基因，"HuidaGene"), a global clinical-stage biotechnology company focused on developing CRISPR-based programmable genomic medicines, today announced the first patient has been dosed in the multinational, master-protocol Phase 1/2a clinical trial (NCT05906953; CTR20232920) of HG004 gene therapy drug, or the STAR (Safety and efficacy Trial of HG004 for leber congenital Amaurosis related to Rpe65 gene mutations) study, an adeno-associated virus 9 (AAV9) gene replacement therapy candidate for the treatment of inherited retinal dystrophies caused by RPE65 mutations (RPE65-IRD). "Commonly used AAV2 for RPE65-related retinal diseases requires high total vector dose and large injection volume emerging to safety concerns such as retinal detachment etc," said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-founder and Chief Executive Officer of HuidaGene. "The efficient retinal transduction in the targeted RPE layers using HG004 for retinal disease allowing to lower both the total vector dose and injection volume has been validated in the HG00401 clinical trial for treating adults and children with LCA2 and makes it likely that this therapy can also potentially treat the IRD caused by RPE65 gene, as suggested by the U.S. FDA. The unmet need is huge for over 55,000 patients living with RPE65-IRD worldwide. Everyone at HuidaGene is excited about this significant milestone as we're working closely with the sites in China and U.S. to develop a safer and more efficacious 'once-and-done' therapy for the RPE65-IRD patient community globally." HG004 is an investigational gene replacement therapy product independently developed by HuidaGene. This HG004 therapy uses the recombinant AAV9 (AAV9) vector to deliver a functional human RPE65 gene to the retina and to restore, treat, and prevent blindness of children and adults with RPE65-IRDs. HG004 was granted both orphan drug designation ( ) and rare pediatric disease designation ( ) by the U.S. Food and Drug Administration (FDA) this year. The HG00401 clinical trial (NCT06088992) for Leber congenital amaurosis type 2 (LCA2) using the same product of HG004 in this multinational, multi-center, master-protocol clinical trial (HG00402; NCT05906953) for RPE65-IRDs also recently announced that the last-patient-dose has been completed with significant visual improvement and no safety concerns in both adult and pediatric populations. "Following the completion of last-patient-dose in the IIT study on October 24, the successful completion of first-patient-dose in the HG004 multinational trial this week means that that company has reached another important milestone, particularly for the global footprint. We'll work diligently to advance this global multinational, master-protocol Phase 1/2a clinical trial to support simultaneous drug marketing approval and commercialization in the future," said Xuan Yao, Ph.D., Co-founder, President, and GM for Greater China of HuidaGene. "This milestone highlights our commitment to developing novel genetic medicines to patients with high, unmet needs and the strong execution capabilities of our team. We hope that this multi-regional trial with the potential to be registrational globally can bring new, transformative therapeutic options for individuals living with RPE65-IRD worldwide." About RPE65 Mutation-Associated Inherited Retinal Dystrophies (RPE65-IRD) Inherited retinal dystrophies (IRDs) are a group of rare blinding conditions caused by mutations in any 1 of more than 250 genes. Leber's congenital amaurosis (LCA), severe early childhood-onset retinal dystrophy (SECORD), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP) which may all be grouped under the heading of IRDs caused by the mutations in RPE65 gene (RPE65-IRDs), are considered to represent a phenotypic continuum of the same disease. The RPE65-IRDs with a typical onset between birth and 5 years of age exhibit several common clinical findings, chiefly night blindness (light staring with profound nyctalopia and nystagmus), progressive loss of visual fields, and loss of central vision. Given the often severe and early visual loss associated with RPE65-IRDs, other areas of development including speech, social skills, and behavior may also be delayed. About Multinational, Master-Protocol Clinical Trial of HG004 (NCT05906953; CTR20232920) This multinational, multicenter, multiple-cohort, dose-finding, and master-protocol clinical trial is designed to evaluate the safety, tolerability, and efficacy of HG004 in patients with inherited retinal dystrophies caused by RPE65 mutations. The primary endpoints include adverse events, certain laboratory measures, and ophthalmic examinations. This HG00402 study will also assess visual function via. multi-luminance mobility test (MLMT) where subjects will be navigating a mobility course under a variety of light levels. Following the completion of the primary study period, subjects will continue to be assessed in a long-term follow-up study of HG004. For more information, please contact: HG00402@huidagene.com or visit About HuidaGene - 辉大基因 HuidaGene Therapeutics (辉大基因) is a global clinical-stage biotechnology company focusing on discovering, engineering, and developing novel gene-editing tools and gene therapies to rewrite the future of genomic medicine. Based in Shanghai and New Jersey, HuidaGene is committed to addressing patients' needs globally with various preclinical therapeutic programs covering ophthalmology and neurology. We are currently advancing clinical programs of HG004 in inherited retinal disease caused by RPE65 mutations (which has been granted both ODD and RPDD by U.S. FDA), HG202 CRISPR/Cas13Y RNA-editing in neovascular age-related macular degeneration (nAMD), and our preclinical pipeline, including programs HG301 CRISPR/Cas12 DNA-editing in retinitis pigmentosa, HG204 CRISPR/Cas13Y RNA-editing in neurodevelopmental disease of MECP2 duplication syndrome (MDS) (which has been granted RPDD and ODD by U.S. FDA), and HG302 CRISPR/Cas12 DNA-editing in neuromuscular diseases of Duchenne muscular dystrophy (DMD) etc. Company's CRISPR-based therapeutics offer the potential to cure patients with life-threatening conditions by repairing the cause of their disease. HuidaGene is committed to transforming the future of genome-editing medicine. For more information, please visit or follow us on LinkedIn at

HG004 is the first China-developed AAV gene therapy medicine to be evaluated in a multinational, master-protocol clinical trial for patients with inherited retinal dystrophies caused by mutations in RPE65 gene HG004 is also first China independently-developed gene therapy drug granted both ODD and RPDD by the U.S. FDA HG004 is Company's first product candidate from robust pipeline of ophthalmology and neurology advances into the clinic SHANGHAI and CLINTON, N.J., Oct. 31, 2023 /PRNewswire/ -- HuidaGene Therapeutics (辉大基因，"HuidaGene"), a global clinical-stage biotechnology company focused on developing CRISPR-based programmable genomic medicines, today announced the first patient has been dosed in the multinational, master-protocol Phase 1/2a clinical trial (NCT05906953; CTR20232920) of HG004 gene therapy drug, or the STAR (Safety and efficacy Trial of HG004 for leber congenital Amaurosis related to Rpe65 gene mutations) study, an adeno-associated virus 9 (AAV9) gene replacement therapy candidate for the treatment of inherited retinal dystrophies caused by RPE65 mutations (RPE65-IRD). "Commonly used AAV2 for RPE65-related retinal diseases requires high total vector dose and large injection volume emerging to safety concerns such as retinal detachment etc," said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-founder and Chief Executive Officer of HuidaGene. "The efficient retinal transduction in the targeted RPE layers using HG004 for retinal disease allowing to lower both the total vector dose and injection volume has been validated in the HG00401 clinical trial for treating adults and children with LCA2 and makes it likely that this therapy can also potentially treat the IRD caused by RPE65 gene, as suggested by the U.S. FDA. The unmet need is huge for over 55,000 patients living with RPE65-IRD worldwide. Everyone at HuidaGene is excited about this significant milestone as we're working closely with the sites in China and U.S. to develop a safer and more efficacious 'once-and-done' therapy for the RPE65-IRD patient community globally." HG004 is an investigational gene replacement therapy product independently-developed by HuidaGene. This HG004 therapy uses the recombinant AAV9 (AAV9) vector to deliver a functional human RPE65 gene to the retina and to restore, treat, and prevent blindness of children and adults with RPE65-IRDs. HG004 was granted both orphan drug designation ( ) and rare pediatric disease designation ( ) by the U.S. Food and Drug Administration (FDA) this year. The HG00401 clinical trial (NCT06088992) for Leber congenital amaurosis type 2 (LCA2) using the same product of HG004 in this multinational, multi-center, master-protocol clinical trial (HG00402; NCT05906953) for RPE65-IRDs also recently announced that the last-patient-dose has been completed with significant visual improvement and no safety concerns in both adult and pediatric populations. "Following the completion of last-patient-dose in the IIT study on October 24, the successful completion of first-patient-dose in the HG004 multinational trial this week means that that company has reached another important milestone, particularly for the global footprint. We'll work diligently to advance this global multinational, master-protocol Phase 1/2a clinical trial to support simultaneous drug marketing approval and commercialization in the future," said Xuan Yao, Ph.D., Co-founder, President, and GM for Greater China of HuidaGene. "This milestone highlights our commitment to developing novel genetic medicines to patients with high, unmet needs and the strong execution capabilities of our team. We hope that this multi-regional trial with the potential to be registrational globally can bring new, transformative therapeutic options for individuals living with RPE65-IRD worldwide." About RPE65 Mutation-Associated Inherited Retinal Dystrophies (RPE65-IRD) Inherited retinal dystrophies (IRDs) are a group of rare blinding conditions caused by mutations in any 1 of more than 250 genes. Leber's congenital amaurosis (LCA), severe early childhood-onset retinal dystrophy (SECORD), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP) which may all be grouped under the heading of IRDs caused by the mutations in RPE65 gene (RPE65-IRDs), are considered to represent a phenotypic continuum of the same disease. The RPE65-IRDs with a typical onset between birth and 5 years of age exhibit several common clinical findings, chiefly night blindness (light staring with profound nyctalopia and nystagmus), progressive loss of visual fields, and loss of central vision. Given the often severe and early visual loss associated with RPE65-IRDs, other areas of development including speech, social skills, and behavior may also be delayed. About Multinational, Master-Protocol Clinical Trial of HG004 (NCT05906953; CTR20232920) This multinational, multicenter, multiple-cohort, dose-finding, and master-protocol clinical trial is designed to evaluate the safety, tolerability, and efficacy of HG004 in patients with inherited retinal dystrophies caused by RPE65 mutations. The primary endpoints include adverse events, certain laboratory measures, and ophthalmic examinations. This HG00402 study will also assess visual function via. multi-luminance mobility test (MLMT) where subjects will be navigating a mobility course under a variety of light levels. Following the completion of the primary study period, subjects will continue to be assessed in a long-term follow-up study of HG004. For more information, please contact: HG00402@huidagene.com or visit About HuidaGene - 辉大基因 HuidaGene Therapeutics (辉大基因) is a global clinical-stage biotechnology company focusing on discovering, engineering, and developing novel gene-editing tools and gene therapies to rewrite the future of genomic medicine. Based in Shanghai and New Jersey, HuidaGene is committed to addressing patients' needs globally with various preclinical therapeutic programs covering ophthalmology and neurology. We are currently advancing clinical programs of HG004 in inherited retinal disease caused by RPE65 mutations (which has been granted both ODD and RPDD by U.S. FDA), HG202 CRISPR/Cas13Y RNA-editing in neovascular age-related macular degeneration (nAMD), and our preclinical pipeline, including programs HG301 CRISPR/Cas12 DNA-editing in retinitis pigmentosa, HG204 CRISPR/Cas13Y RNA-editing in neurodevelopmental disease of MECP2 duplication syndrome (MDS) (which has been granted RPDD and ODD by U.S. FDA), and HG302 CRISPR/Cas12 DNA-editing in neuromuscular diseases of Duchenne muscular dystrophy (DMD) etc. Company's CRISPR-based therapeutics offer the potential to cure patients with life-threatening conditions by repairing the cause of their disease. HuidaGene is committed to transforming the future of genome-editing medicine. For more information, please visit or follow us on LinkedIn at View original content to download multimedia: SOURCE HuidaGene Therapeutics

HG004 is a one-time, direct-to-RPE treatment of inherited retinal disease caused by mutations in the RPE65 gene ~10-fold lower vector doses in multiregion, multicenter HG00402 trial than other AAV2 gene therapy clinical trials HG004 was previously granted orphan drug designation (ODD) for RPE65-IRD on 31 March 2023 SHANGHAI and CLINTON N.J., Aug. 7, 2023 /PRNewswire/ -- HuidaGene Therapeutics (辉大基因，"HuidaGene"), a clinical-stage biotechnology company focused on developing CRISPR-based programmable genomic medicines, today announced the U.S. Food and Drug Administration (FDA) had granted Rare Pediatric Disease Designation (RPDD) to HG004 for the treatment of inherited retinal disease caused by RPE65 mutations (RPE65-IRDs). The FDA grants RPDD to incentive development of new treatments for serious or life-threatening diseases that primarily affect children ages 18 years or younger with fewer than 200,000 people affected in the U.S. The RPDD program allows for a sponsor who receives an approval to qualify for a priority review voucher (PRV) that can be deemed to receive an expedited six-month priority review for any subsequent marketing application or may be sold or transferred. PRVs have historically commanded prices in excess of $100 million USD with the highest price paid for a PRV was $350 million USD. For a large company launching a billion-dollar drug, the six-month acceleration in regulatory review can be of substantial economic value. Most recently, Sarepta Therapeutics sold a PRV for $102 million USD. "This Rare Pediatric Disease designation from the US FDA highlights the significant unmet medical need that HuidaGene is seeking to address with HG004 for RPE65-IRDs," said Alvin Luk, Ph.D., M.B.A., C.C.R.A., Co-founder and Chief Executive Officer of HuidaGene. "HG004 was granted both RPDD and orphan drug designation (ODD) by the US FDA in March, allowing tax credits for clinical development, exemptions for certain FDA application fees, 7-year of market exclusivity, and assistance in the drug development process. We look forward to advancing HG004 in the clinic and remain steadfast in our commitment to answering patients worldwide." "We are pleased to have received another significant regulatory feedback from the US FDA underscoring the dire need for a treatment option of this devastating inherited blindness," said Linyu Shi, Ph.D., Co-founder and Chief Scientific Officer of HuidaGene. "Data from our preclinical studies have shown that HG004 demonstrates significant superiority than AAV2-hRPE65 (LUXTURNA like) in the recovery of retinal function of the Rpe65-/- mice. We are committed to delivering transformative genetic medicines for rare genetic diseases globally." About Inherited Retinal Disease Caused by RPE65 Mutations Inherited retinal disease (IRD) is a group of rare blinding conditions caused by mutations in any 1 of more than 250 genes. Leber's congenital amaurosis (LCA), severe early childhood-onset retinal dystrophy (SECORD), early-onset severe retinal dystrophy (EOSRD), and retinitis pigmentosa (RP), which may all be grouped under the heading of inherited retinal disease caused by RPE65 mutations (RPE65-IRD), are considered to represent a phenotypic continuum of the same disease. The RPE65-IRD with a typical onset between birth and five years of age exhibits several common clinical findings, chiefly night blindness, progressive loss of visual fields, and loss of central vision. Given the often severe and early visual loss associated with RPE65-IRD, other areas of development, including speech, social skills, and behavior, may also be delayed. About HuidaGene -辉大基因 HuidaGene Therapeutics (辉大基因) is a global clinical-stage biotechnology company focusing on discovering, engineering, and developing CRISPR-based genetic medicine to rewrite the future of genomic medicine. Based in Shanghai and New Jersey, HuidaGene is committed to addressing patients' needs globally with various preclinical therapeutic programs covering ophthalmology, otology, myology, and neurology. We are currently advancing clinical programs in inherited retinal disease caused by RPE65 mutations and our preclinical pipeline, including programs in neovascular age-related macular degeneration, retinitis pigmentosa, hereditary hearing loss, Duchenne muscular dystrophy, and MECP2 duplication syndrome. Company's CRISPR-based therapeutics offer the potential to cure patients with life-threatening conditions by repairing the cause of their disease. HuidaGene is committed to transforming the future of genome-editing medicine. For more information, please visit or follow us on LinkedIn at