HuidaGene's CRISPR/Cas13 RNA-Editing Therapy HG202 Cleared for US Trial in Macular Degeneration
Key Insights
HuidaGene Therapeutics (search)' HG202, a CRISPR/Cas13 RNA-editing therapy, has received FDA clearance for a Phase 1 clinical trial to treat neovascular age-related macular degeneration (search) (nAMD).
HG202 aims to knock down VEGF-A (search) mRNA expression and has shown an 87% decrease in choroidal neovascularization area in preclinical studies, outperforming anti-VEGF antibodies.
The Phase 1 BRIGHT trial (NCT06623279) will assess the safety and tolerability of HG202, with secondary endpoints including best-corrected visual acuity and central retinal thickness.
HuidaGene Therapeutics (search) has received FDA clearance for its Investigational New Drug (IND) application for HG202, a CRISPR/Cas13 RNA-editing therapy intended for the treatment of neovascular age-related macular degeneration (search) (nAMD). This clearance enables a Phase 1 clinical trial to proceed in the United States. HG202 represents a novel approach to addressing nAMD by targeting and knocking down the expression of VEGF-A (search) mRNA.
HG202: A Novel Approach to nAMD Treatment
HG202 is distinguished as the first CRISPR/Cas13Y RNA-targeting therapy to receive clinical trial clearance from the FDA, marking a significant milestone in the field of RNA editing. Preclinical research demonstrated that HG202 achieved an 87% reduction in choroidal neovascularization (CNV) area in laser-induced CNV mice, surpassing the performance of traditional anti-VEGF antibodies and adeno-associated virus (AAV) vector-based anti-VEGF gene therapy.
Alvin Luk, PhD, MBA, CCRA, cofounder and CEO of HuidaGene, stated, "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." He further noted the promising results from in vitro and in vivo preclinical studies, as well as the first-in-human 'SIGHT-I' trial, which led to the decision to pursue FDA approval. Preliminary data from these studies were presented at ARVO, ASGCT, EURETINA, and ESGCT earlier this year.
BRIGHT Clinical Trial: Assessing Safety and Tolerability
With the IND clearance secured, HuidaGene plans to initiate the open-label, multicenter Phase 1 BRIGHT clinical trial (NCT06623279). The primary endpoint of the BRIGHT trial is to evaluate the safety and tolerability of HG202 following a single dose at various dose levels. Secondary endpoints include assessments of best-corrected visual acuity (BCVA), central retinal thickness (CRT), and the need for anti-VEGF rescue injections.
Xin Zhang, MD, MSc, COO and CMO of HuidaGene, highlighted the unmet need in AMD treatment, stating, "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." She emphasized the importance of developing safe and effective treatment options for AMD patients who have not responded well to anti-VEGF therapies. The BRIGHT trial aims to explore safety and efficacy trends across different doses of HG202.
HG004 for Leber Congenital Amaurosis Type 2 (LCA2)
In addition to HG202, HuidaGene is also advancing HG004 (AAV9-hRPE65), an AAV vector-based gene therapy designed to treat Leber congenital amaurosis type 2 (search) (LCA2) associated with mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65 (search)). 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.
Peiquan Zhao, MD, Director of the Ophthalmology Department at Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, reported substantial vision restoration in LCA2 patients with no existing treatment options in China. Following a single administration of HG004, all patients showed improvement in retinal sensitivity, with no serious adverse events observed, including retinal detachment. These findings mark the first time the LIGHT study data has been discussed in an oral presentation at an international conference.