Hui Genomics: The first gene therapy drug HG004 was approved as an orphan drug by the US FDA

The company announced that its new eye gene therapy drug HG004, which was designed and developed by the US Food and Drug Administration (FDA), was granted Orphan drug designation (ODD) for the treatment of inherited retinal diseases caused by the RPE65 mutation.

"The US orphan drug designation marks another important milestone in the development of HG004 following its IND approval in January," said Dr. Xuen Yao, co-founder and CEO of Hui Genomics. This not only demonstrates the FDA's approval of HG004, but also demonstrates the significant clinical value of this therapy for patients with severe visual impairment or blindness caused by RPE65 mutations. We are now accelerating the clinical development of HG004 to provide safe, long-term and high-quality treatment options for patients with RPE65 mutation-related inherited retinal diseases, and to more quickly realize Fujinus' vision of benefiting patients around the world."

The FDA Orphan Drug Act encourages the treatment, diagnosis, or prevention of rare diseases. Orphan drug designation applies to drugs and biologics with rare diseases affecting less than 200,000 people in the United States each year. And to give policy support related products (https://www.fda.gov/patients/rare-diseases-fda). HG004 has been recognized as an orphan drug by the FDA, which will facilitate its subsequent research and development, registration and commercialization in the United States. HG004 will have the opportunity to enjoy certain positive policy support, including, but not limited to, tax deductions for clinical trial fees, exemption of NDA/BLA application fees, access to special research and development funds, fast-track approval green channel, and seven years of US market exclusivity and protection from patents after launch.

In January 2023, HG004 new drug application (IND) clinical trials for FDA approval, and plans on the international multicenter clinical trials (blockbuster | fai big gene is the first gene therapy drug IND is approved in the United States, will undertake the international multicenter clinical trial). At present, China's National Medical Products Administration (NMPA) has accepted the application for clinical trials of HG004 injection.

RPE65 mutations associated with inherited retinal diseases

Hereditary retinal dystrophy (IRDs) is a rare blinding disease caused by genetic mutations. More than 250 genes have been reported to cause the disease. Mutations in the RPE65 gene may cause Leber congenital amaurosis (LCA), severe early-onset childhood retinal dystrophy (SECORD), early-onset severe retinal dystrophy (EOSRD), or retinitis pigmentosa (RP), which are all considered RPE65-mutated retinopathy. Representing a phenotypic continuum of the same disease. RPE65 mutation-associated retinopathy usually develops between birth and 5 years of age, and its main clinical manifestations include night blindness (gazing with severe night blindness and nystagmus), progressive visual field loss, and central vision loss. The proportion of patients meeting the World Health Organization (WHO) diagnostic criteria for blindness (biallelic RPE65 mutation) increases with age, reaching 100% after age 40. Severe and early vision loss due to RPE65 mutation-associated retinopathy may also result in delayed development of other functions such as language, social interaction, and behavior.

About HG004

HG004 injection is a novel ophthalmic gene therapy agent in development for the treatment of RPE65-mutation-associated retinopathy. It uses a recombinant adeno-associated virus vector to deliver a functional human RPE65 gene to the retina to restore, treat and prevent blindness in children and adults with RPE65-mutation-associated IRD. The company independently developed a Rpe65 gene knockout mouse model using CRISPR gene editing technology, which successfully simulated the retinal phenotype and function in patients with RPE65 gene mutation-associated retinopathy. Based on a preclinical comparison of the same dose of HG004 and adeno-associated virus serotype 2(AAV2), Rpe65 knockout mouse models showed a 67.6% and 35.8% improvement in retinal function at week 17 after a single injection, respectively. HG004 shows better retinal pigment epithelium (RPE) transduction efficiency than AAV2 and is expected to reduce the total vector dose, thereby reducing the risk of AAV vector associated immunogenicity or ocular adverse events.