HuidaGene Receives NMPA IND Approval for Its AAV Gene Therapy HG004

Recently, HuidaGene Therapeutics announced that the Investigational New Drug (IND) application for HG004, its first independently developed ophthalmic gene therapy drug, has been approved by the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA). This milestone marks the candidate’s official entry into full-scale international multicenter clinical development. Previously, HG004 received IND clearance from the U.S. Food and Drug Administration (FDA) in January this year and Orphan Drug Designation (ODD) from the FDA in March.

Dr. Yao Xuan, Co-founder and Chief Executive Officer of HuidaGene, said, “The successive approvals of HG004’s IND applications by the U.S. FDA and China’s CDE represent an important milestone in HuidaGene’s R&D progress and a strong recognition of our team’s outstanding innovation and R&D capabilities. At the same time, the simultaneous approval by the FDA and NMPA of HG004’s international, multiregional and multicenter Master Protocol also makes HuidaGene the first gene therapy company in China to achieve an international multiregional and multicenter clinical development strategy under the same Master Protocol in the field of gene therapy, greatly accelerating HuidaGene’s globalization journey. We would like to thank our team members for their concerted efforts over the four years since the company’s establishment and operation, as well as our partners and relevant regulatory authorities for their strong support. Going forward, we will spare no effort in advancing the clinical development of HG004 and continue to research and develop more independently innovative gene therapy products, so that more safe and effective innovative medicines can benefit patients and families worldwide as early as possible.”

Dr. Lu Yingming, a member of HuidaGene’s Scientific Advisory Board, said, “The HG004 program aims to develop a one-time, non-AAV2 gene replacement therapy to provide a treatment option for children and adults worldwide with severe visual impairment or blindness caused by RPE65 mutation-associated inherited retinal disease (IRD). As China’s first ophthalmic gene therapy drug to adopt the same Master Protocol for an international multiregional and multicenter clinical trial, the HuidaGene team will conduct an in-depth and comprehensive evaluation of HG004’s clinical safety, tolerability, efficacy and durability in global clinical development, with the goal of bringing patients an innovative therapy with greater clinical value and higher product quality.”

“HG004 Injection is a novel ophthalmic gene therapy drug intended for the treatment of RPE65 mutation-associated retinal disease. We have obtained high-quality preclinical data to support the upcoming international multiregional and multicenter clinical trial. The initial effective dose of HG004, approximately 1/25 of the vector dose, is significantly lower than that of the approved AAV2-hRPE65 gene therapy product LUXTURNA, and the required subretinal injection volume is smaller. This is expected to substantially reduce the risk of AAV vector-related immunogenicity or ocular adverse events in humans,” said Dr. Yao Xuan. “In a previous investigator-initiated clinical trial (IIT) conducted at Xinhua Hospital in Shanghai, China, encouraging preliminary efficacy results were achieved, with substantial and meaningful vision restoration observed in both adult and pediatric patients treated with HG004.”

About the International Multiregional and Multicenter Clinical Trial of HG004

HG004 is being evaluated in a multinational, multicenter, multicohort, dose-exploration study in adult and pediatric patients with RPE65-associated retinal disease. The same Master Protocol will be adopted across different countries and regions. The objective of the study is to evaluate the safety, tolerability, efficacy and long-term clinical durability of a single administration of HG004 through Week 52. Primary endpoints include adverse events, specific laboratory tests and ophthalmic examinations.

The study will also assess visual function using the internationally standardized multi-luminance mobility test (MLMT). In addition, subjects will continue to be evaluated in a long-term follow-up study of HG004.

About RPE65 Mutation-Associated Inherited Retinal Disease

Inherited retinal dystrophies (IRDs) are a group of rare blinding diseases caused by genetic mutations, with more than 250 disease-causing genes reported to date. Mutations in the RPE65 gene may lead to Leber congenital amaurosis (LCA), severe early childhood-onset retinal dystrophy (SECORD), early-onset severe retinal dystrophy (EOSRD), or retinitis pigmentosa (RP). These conditions are collectively considered RPE65 mutation-associated retinal disease and represent a phenotypic continuum of the same disease.

RPE65 mutation-associated retinal disease typically develops between birth and five years of age. Its main clinical manifestations include night blindness, characterized by poor fixation with severe nyctalopia and nystagmus, progressive visual field loss, and loss of central vision. The proportion of patients meeting the World Health Organization (WHO) diagnostic criteria for blindness due to biallelic RPE65 mutations increases with age, reaching 100% after the age of 40.

Severe and early vision loss caused by RPE65 mutation-associated retinal disease may also lead to developmental delays in other functions, including language, social and behavioral development.