HuidaGene Therapeutics’ CRISPR/Cas13 RNA-Editing Therapy HG202 Gets Greenlight for US Trial in Age-Related Macular Degeneration
According to HuidaGene, it is the first CRISPR/Cas13Y RNA-targeting therapy to receive clearance for a clinical trial from the FDA or any other regulatory agency.
HuidaGene Therapeutics’ HG202, an investigational CRISPR/Cas13 RNA-editing therapy intended to treat neovascular age-related macular degeneration (nAMD), has received clearance of an investigational new drug (IND) application from the FDA, enabling a phase 1 clinical trial.1
HG202 is intended to address nAMD via knock-down of expression of VEGF-A mRNA. According to HuidaGene, it is the first CRISPR/Cas13Y RNA-targeting therapy to receive clearance for a clinical trial from the FDA or any other regulatory agency. It is also the only RNA-targeted therapy currently in clinical trials for the treatment of nAMD. In preclinical research, HG202 effected an 87% decrease in choroidal neovascularization (CNV) area in laser-induced CNV mice, thus performing better on this metric than antiVEGF antibodies and adeno-associated virus (AAV) vector-based antiVEGF gene therapy.
“This open IND for HG202 by the United States FDA – the first regulator to have cleared CRISPR/Cas13 for clinical development – represents an important milestone for HuidaGene and the entire CRISPR gene-editing field of RNA editing,” Alvin Luk, PhD, MBA, CCRA, the cofounder and chief executive officer of HuidaGene, said in a statement.1 “We chose to go to the FDA because HG202 demonstrated good results in the invitro, in vivo preclinical studies and first-in-human ‘SIGHT-I’ trial. In September 2023, we dosed the world’s first novel CRISPR/Cas13 RNA-editing therapy in humans, and we recently presented preliminary data at the ARVO, ASGCT, EURETINA, and ESGCT this year. The rigor of our clinical data in China using a nonreceptor binding pathway approach through Cas13 RNA editor to partially knock down the mRNA expression of VEGFA brings the potential to AMD patients.”
In light of the IND clearance, HuidaGene intends to carry out the planned open-label, multicenter phase 1 BRIGHT clinical trial (NCT06623279). Safety and tolerability following a single dose at different dose levels constitutes BRIGHT’s primary end point. Outcomes on best-corrected visual acuity (BCVA), central retinal thickness (CRT), and necessitation of antiVEGF rescue injections will serve as secondary end points for the study.
“Up to 46% of AMD patients using antiVEGF reagents have shown poor response or have developed tachyphylaxis with antiVEGF therapies, resulting in irreversible vision loss,” Xin Zhang, MD, MSc, the chief operations officer and chief medical officer of HuidaGene, added to the statement.1 “AMD patients deserve safe and effective treatment options. This is a critical step toward overcoming the challenges of AMD patients who have failed antiVEGF therapies. In the proposed BRIGHT clinical trial, we aim to explore safety and efficacy trends at different doses of HG202. We look forward to beginning enrollment soon.”
In addition to HG202, HuidaGene is also developing HG004 (AAV9-hRPE65), an AAV vector-based gene therapy intended to treat Leber congenital amaurosis type 2 (LCA2) associated with mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65).2 Data from the phase 1 LIGHT clinical trial (NCT06088992) evaluating HG004 were recently presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland.
“We saw substantial restoration of vision in patients living with Leber congenital amaurosis who have no treatment options currently in China,” senior author Peiquan Zhao, MD, the director of the Ophthalmology Department at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, said in a statement about the updated data.2 “After only a single, one-time administration, all of the patients given HG004 had improvement in retinal sensitivity and there were no serious adverse events, including retinal detachment, have been observed. This trial data of the ‘LIGHT’ study is the first time been discussed in an oral presentation at an international conference. As the principal investigator of the study, I am committed to working with global stakeholders to bring this safe and effective treatment to patients with LCA and bring light to patients with ophthalmic diseases worldwide.”
