LCA2 Gene Therapy Shows Visual, Retinal Improvements at Low Doses


No serious adverse events or significant retinal atrophy occurred.

HG004 (AAV9-hRPE65; HuidaGene) gene therapy was well-tolerated and improved some visual and retinal function in patients with Leber congenital amaurosis type 2 (LCA2) associated with mutations in the retinal pigment epithelium-specific 65-kDa protein gene (RPE65).1

Updated data from the phase 1 LIGHT study (NCT06088992) of HG004 were presented at the American Society of Gene & Cell Therapy (ASGCT) 27th Annual Meeting, held May 7 to 10, 2024, in Baltimore, Maryland, by Ping Fei, Xinhua Hospital affiliated to Shanghai Jiao Tong University, Shanghai, China.1

“We saw substantial restoration of vision in patients living with Leber congenital amaurosis who have no treatment options currently in China,” senior author Prof. Peiquan Zhao, Director of OphthalmologyDepartment, 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.”

Investigators have dosed 9 participants (4 adults, 5 children) in the LIGHT study as of the cutoff date in December 2023, 3 each in 3 cohorts evaluating low-dose, mid-dose, and high-dose HG004. No serious adverse events (AEs), signs of inflammation, acute renal toxicity, or clinically determined immune responses have been observed. There have also been no severe ocular surgery complications and most AEs were mild, transient, and spontaneously resolved.1

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Participants had no significant or progressive retinal atrophy. Preliminary efficacy findings evaluating best-corrected visual acuity (BCVA), full-field stimulus threshold (FST), and kinetic visual field (KVF) tests were promising, with these measures improving by an average of +11 letters, -2.268 log10cd*s/m2, and +554.25 deg2 (1114e) respectively at 6 months post-treatment. The average BCVA improvement was +14.3 letters at 2 months and +7.5 letters at 3 months post injection; the average FST improvement was –2.774 log10cd*s/m2 at 2 months and –1.413 log10cd*s/m2 at 3 months post injection; and the average KVF improvement was +817.17 deg2 (1114e) at 2 months and +958.30 deg2 (1114e) at 3 months post injection. Most participants had at least a 2-log unit increase in pupillary light responses. Notably, the poster emphasized that these dose levels are 1/25 to 1/15 folds lower than approved gene therapies for LCA2.1

“We look forward to sharing recent progress in preclinical and clinical data on our HG202 CRISPR RNA-targeting therapy program for AMD and HG004 gene replacement therapy program for LCA2 which has been granted both orphan drug and rare pediatric disease designations for inherited retinal dystrophies associated with RPE65 mutations by the U.S. FDA,” Alvin Luk, PhD, MBA, CCRA, cofounder and CEO, HuidaGene, commented in a recent statement.2

1. Fei P, Yang Y, Peng J, et al. Preliminary Safety and Efficacy of HG004 Gene Therapy Trial for Leber's Congenital Amaurosis Associated with Mutations in RPE65 Gene. Presented at: ASGCT 27th Annual Meeting, May 7-10; Baltimore, Maryland. Abstract #915
2. HuidaGene Orally Presents Data Highlighting Strength of Ophthalmology Portfolio at the 2024 Association for Research in Visual and Ophthalmology Annual Meeting. News release. HudaGene. April 22, 2024.
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