IND Cleared for Leber Hereditary Optic Neuropathy Gene Therapy


NFS-02 previously received orphan drug designation from the FDA in January of this year.

Neurophth Therapeutics’ NFS-02 (rAAV2-ND1), an investigational gene therapy intended to treat Leber hereditary optic neuropathy (LHON) associated with mutations in the NADH-dehydrogenase subunit 1 gene (ND1), has received clearance of its investigational new drug (IND) application from the FDA.1

NFS-02 is designed to be administered as an ophthalmic injection and is intended to deliver a codon-optimized copy of ND1 via an adeno-associated viral serotype 2 vector (rAAV2). It previously received orphan drug designation (ODD) from the FDA in January of this year. Neurophth Therapeutics plans to evaluate the safety and efficacy of the therapy in a multicenter, single-arm, open-label, dose-finding phase 1/2 clinical trial for patients with LHON associated with ND1 mutations.

“The approval of this IND marks a significant milestone for the Company,” Xiaoning Guo, PhD, chief medical officer, Neurophth Therapeutics, said in a statement regarding the news.1 “Based on encouraging preclinical data, we believe that this gene therapy drug candidate holds promise to become a safe and effective treatment for patients. We are excited to proceed with our NFS-02 clinical trial plans for treating ND1-LHON patients, and we look forward to initiate the enrollment of our US clinical trial early next year.”

The news comes several months after the company announced the dosing of the first patient in phase 3 of the phase 1/2/3 GOLD clinical trial (NCT04912843) for 1 of its other investigational gene therapies, NR082, in September 2022.2 NR082 is intended to treat LHON associated with mutations in the ND4 gene. It received ODD from the FDA in September 2020 and from the European Medicines Agency in January 2022, as well as breakthrough therapy designation from China’s Center for Drug Evaluation in July 2022.2-4 At the time of the September 2022 announcement, the company noted that NR082 has been evaluated in 3 previous investigator-initiated trials involving 186 patients with LHON and was well-tolerated and demonstrated efficacy in improving visual acuity. Clinical durability was shown to last up to 90 months in the first trial.

In addition to NFS-02 and NR082, the company also has several other therapies in preclinical development for indications including optic neuropathy (NFS-04), autosomal dominant optic atrophy (NFS-05), and vascular retinopathy (NFS-10), plus several therapies for which no indication has been disclosed.5

“We are thrilled to have received IND clearance for NFS-02, marking our second program to reach clinical development,” Bin Li, founder, chairman, and CEO, Neurophth Therapeutics, added to the statement.1 “Our first drug targets ND4-LHON, and this time we continue to advance our pipeline of ophthalmic gene therapy and develop drugs for patients with ND1-LHON, hoping that every patient can embrace a bright future.”

1. Neurophth receives IND clearance from FDA for AAV-ND1 gene therapy of LHON. News release. Neurophth Therapeutics, Inc. December 19, 2022. 
2. Neurophth announces first patient dosed in Phase III clinical trial for the gene therapy treatment of LHON. News release. Neurophth Therapeutics, Inc. September 27, 2022. 
3. Neurophth Therapeutics' treatment of Leber's hereditary optic neuropathy gene therapy NR082 was granted orphan drug designation by EMA. News release. Neurophth Therapeutics, Inc. January 24, 2022. 
4. China CDE grants breakthrough therapy designation (BTD) to Neurophth’s NR082 in LHON. News release. Neurophth Therapeutics, Inc. July 15, 2022. 
5. Neurophth Therapeutics. Pipelines. Website Accessed December 21, 2022. 
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