Neurophth Biologics Receives CDE Acceptance for Clinical Trial Application of Ophthalmic Gene Therapy NR082 (NFS-01) for LHON

Source: Medical Perspective

On January 19, the Center for Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) announced that the clinical trial application for NR082 ophthalmic injection (Project NFS-01), a gene therapy developed by Neurophth for ophthalmic use, had been submitted and accepted. Previously, NR082 had been granted Orphan Drug Designation by the U.S. Food and Drug Administration (FDA) for the treatment of Leber’s Hereditary Optic Neuropathy (LHON) caused by the ND4 mutation.

Screenshot source: CDE official website

Public information indicates that NR082 is the first candidate drug developed by Neurophth, which has previously completed a global, large-sample clinical trial of gene therapy for Leber hereditary optic neuropathy (LHON). In this project, scientists used recombinant adeno-associated virus as a vector to deliver the correct human ND4 gene via intravitreal injection to damaged retinal ganglion cells in patients, thereby repairing the mitochondrial respiratory chain and restoring the vitality and visual function of retinal ganglion cells.

As early as 2011, Neurophth initiated an exploratory clinical trial of NR082 gene therapy in China. The results showed that among the nine patients with LHON caused by ND4 mutations who participated in the trial, seven experienced significant improvement in vision, with best-corrected visual acuity recovering to 0.8. The mean best-corrected visual acuity improved by 0.39 logMAR (equivalent to nearly four lines on the Snellen chart) across all nine patients. Eight patients completed long-term follow-up for nearly eight years, with no serious adverse events reported.

Based on the positive results from earlier studies, NR082 completed an international gene therapy clinical trial involving 159 LHON patients in China and Argentina between 2017 and 2018.

According to a previous press release issued by Neurophth, the reason gene therapy has “excelled” in the treatment of ocular diseases lies in the unique characteristics of the eye: as a closed spherical structure, it allows for localized intraocular injection of drugs with minimal systemic impact, making it well-suited for gene therapy. Furthermore, more than 220 genes are associated with ophthalmic conditions, and mutations in any of these genes can lead to vision loss and blindness. Practice has demonstrated that gene therapy utilizing safe viral vectors to deliver nucleic acid-based therapeutics—aimed at correcting genetic abnormalities or expressing normal gene products—is one of the promising strategies for treating blinding eye diseases.

Leber’s Hereditary Optic Neuropathy (LHON) is a rare maternally inherited mitochondrial disorder characterized by degeneration of retinal ganglion cells, leading to irreversible vision loss and even blindness. Genetic sequencing has revealed that this condition is typically caused by the m.11778G>A mutation in mitochondrial DNA, which affects the NADH dehydrogenase subunit 4 (ND4) gene. This mutation impairs the mitochondrial respiratory chain, resulting in ATP deficiency, oxidative stress in retinal ganglion cells, and subsequent apoptosis.

Currently, there are no effective treatments or cures for LHON in clinical practice, indicating a significant unmet medical need. We hope that the clinical development of Neurophth’s NR082 in China proceeds smoothly, bringing innovative therapies to patients as soon as possible.

▽Follow [WuXi AppTecDe】WeChat Official Account