HuidaGene Therapeutics gains FDA clearance for multinational clinical trial of investigational new drug

HG004 is the company's first IND clearance from the FDA and aims to be more effective than AAV2 products. (Adobe Stock image)

HuidaGene Therapeutics announced the FDA has cleared its investigational new drug (IND) application for the planned, multi-national clinical trial of HG004.

According to a news release by HuidaGene, HG004 will be used for the treatment of patients suffering from RPE65 mutation-associated inherited retinal dystrophies. This is a group of genetic diseases caused by mutations in the RPE65 gene affecting the retina and passed on to children.

Xuan Yao, PhD, co-founder, and chief executive officer of HuidaGene talked about HG004, it being the company's first IND clearance from the FDA and the impact it could have in the release.

"We are thrilled to have received the IND clearance of our HG004 program from US FDA, marking our first IND clearance as a company and our first retinal disorder program to reach clinical development stage," said Xuan Yao. " The goal of the HG004 program is to develop a one-time, non-AAV2 gene replacement therapy to restore, treat, and prevent blindness of children and adults with severe visual impairment or blindness due to RPE65 mutation-associated retinopathies globally."

According to the release, the planned multi-national, multicenter, multiple-cohort, dose-finding clinical trial will evaluate HG004 in adult and pediatric subjects with RPE65 retinopathies under a single master protocol in various countries.

The HG004 project aims to develop a single-injection, non-adeno-associated virus serotype 2 (AAV2) gene replacement therapy, based on the same dose of HG004 and AAV2 clinical trials, according to the company.

Head-to-head preclinical comparisons of HG004 and AAV2 at the same, single dose showed a recovery of retinal functions in mice by 67.6% with HG004 and 35.8% with AAV2 products at week 17 according to the release.

"We are excited by the promise of HG004 to offer a potential transformative treatment better than AAV2-mediated gene replacement therapy," said Hui Yang, PhD, co-founder and chief scientific advisor of HuidaGene. "Our extensive preclinical studies demonstrated superior transduction efficiency and substantial restoration of vision loss at the RPE layer when HG004 compared to AAV2 through our independently-developed RPE65 gene knockout murine disease model, which is found to mimic the retinal phenotypes and functions of patients with RPE65 mutation-associated inherited retinal dystrophies."

According to the company, patients enrolled in the investigator-initiated trial (IIT) in China at the end of 2022 that were progressing toward complete blindness saw a substantial restoration of vision with “nearly 25-fold lower vector doses” of HG004 than the approved AAV2-hRPE65 gene therapy product.

The company expects to initiate the trial in the first half of this year.