HuidaGene’s AAV Gene Therapy HG004 IND Approved by NMPA

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

HuidaGene Co-founder and Chief Executive Officer Dr. Xuan Yao stated, “The IND approvals for HG004 by both the U.S. FDA and China’s CDE represent an important milestone in HuidaGene’s R&D progress and fully recognize the HuidaGene team’s outstanding innovation and R&D capabilities. At the same time, the simultaneous approval of HG004’s international multi-regional, multicenter Master Protocol by the FDA and NMPA has also made HuidaGene the first gene therapy company in China to achieve an international multi-regional, 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 past four years since the company’s establishment and operation, as well as our partners and relevant regulatory authorities for their strong support. Looking ahead, 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. Yingming Lu, a member of HuidaGene’s Scientific Advisory Board, stated, “The HG004 program aims to develop a one-time, non-AAV2 gene replacement therapy to provide a treatment option for children and adult patients worldwide with severe visual impairment or blindness caused by RPE65 mutation-associated inherited retinal disease (IRD). As China’s first ophthalmic gene therapy drug adopting the same international multi-regional, multicenter Master Protocol, the HuidaGene team will conduct an in-depth and comprehensive exploration of HG004’s clinical safety, tolerability, efficacy, and durability during global clinical development, with the goal of delivering an innovative therapy with superior clinical value and higher product quality to patients.”

“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 multi-regional, multicenter clinical trial. The starting effective dose of HG004, at approximately 1/25 of the vector dose, is far lower than that of the approved AAV2-hRPE65 gene therapy product LUXTURNA, and requires a smaller injection volume into the retina, which will significantly reduce the risk of AAV vector-related immunogenicity or ocular adverse events in humans,” said Dr. Xuan Yao. “Previously, in the investigator-initiated 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 HG004 International Multi-Regional, Multicenter Clinical Trial

HG004 is being evaluated in a multinational, multicenter, multi-cohort, 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 this study is to evaluate the safety, tolerability, efficacy, and long-term clinical durability of a single injection 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), and subjects will continue to be evaluated in the long-term follow-up study of HG004.

About RPE65 Mutation-Associated Inherited Retinal Diseases

Inherited retinal dystrophies (IRDs) are a group of rare blinding diseases caused by genetic mutations, with more than 250 pathogenic genes reported to date. Among them, mutations in the RPE65 gene may lead to Leber congenital amaurosis (LCA), severe early-onset childhood retinal dystrophy (SECORD), early-onset severe retinal dystrophy (EOSRD), or retinitis pigmentosa (RP). These diseases are all considered RPE65 mutation-associated retinal diseases and represent a phenotypic continuum of the same disease. RPE65 mutation-associated retinal disease typically develops between birth and five years of age. Its major clinical manifestations include night blindness, staring accompanied by severe night blindness 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, with biallelic RPE65 mutations, increases with age and reaches 100% after the age of 40. Severe and early vision loss caused by RPE65 mutation-associated retinal disease may also result in developmental delays in other functions, including language, social interaction, and behavior.