Neurophth Therapeutics’ ND1-LHON Gene Therapy Trial Doses First Patient


The single-arm, open-label clinical trial will seek to enroll approximately 18 patients aged 18 to 75 years.

The first patient has been dosed in a multiregional phase 1/2 clinical trial (NCT05820152) evaluating Neurophth Therapeutics’ NFS-02 (rAAV2-ND1), an investigational gene therapy intended to treat Leber hereditary optic neuropathy associated with mutations in the NADH-dehydrogenase subunit 1 gene (LHON-ND1).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 (rAAV2) vector.2 The study, which is being conducted in both the United States (US) and China, is led by Jia Qu, MD, and Rong Zhou, MD, professors at the Eye Hospital of Wenzhou Medical University.1 Neurophth originally received clearance of the investigational new drug (IND) applications for the trial from the FDA in December 2022 and from China’s National Medical Products Administration (NMPA) in April 2023. 

Several patients have already received NFS-02 in a separate investigator-initiated trial in China, including a patient from Malta whom Neurophth arranged to have treated.3,4 Xiaoning Guo, PhD, the chief medical officer of Neurophth, reported that the gene therapy showed safety and efficacy in the investigator-initiated study. NFS-02 was previously granted orphan drug designation by the FDA in January 2022.2

“Today’s milestoneis a significant step forward,” Bin Li, MD, PhD, the founder, chairman, and CEO of Neurophth, said in a statement.1 “NFS-02 is Neurophth’s second gene therapy to enter clinical trials, demonstrating the company's strong operations. NFS-02 is currently the only ND1-LHON treatment in development worldwide. In response to patients’ expectations, we are committed to conduct global multiregion, multicenter clinical trials to ensure that it’s on the path towards early drug approval and commercialization in the future.”

The single-arm, open-label clinical trial will seek to enroll approximately 18 patients aged 18 to 75 years. An initial group of 6 participants will be treated with NFS-02 at a dose of 1.5×108 vg, 0.05 mL eye/dose; pending analysis by the trial’s safety review committee, dose escalation or de-escalation may be carried out. In the 6 weeks following administration of the gene therapy, if no more than 1 patient experiences a dose-limiting toxicity (DLT) event in the initial group, a dose of 5.0×108 vg, 0.05 mL eye/dose will be administered in the next 6 patients. Similarly, if no more than 1 patient in this group experiences a DLT event in the 6 weeks after administration, the dose will be escalated to 1.5×109 vg, 0.05 mL eye/dose. If DLT events occur in 2 or more patients in the initial group in the first 6 weeks posttreatment, the dose will be de-escalated to 5.0×107 vg, 0.05 mL eye/dose. The trial’s primary end points are the incidence of adverse events (AEs), serious AEs, and DLTs within 52 weeks of administration of NFS-02.

“In the coming months, we will continue to accelerate the patient enrollment process of the China-US phase 1/2 clinical trial,” Guo added to the statement.1 “We anticipate positive results of the clinical trial and hope that it can bring us closer to achieving the goal of building a brighter future for global patients affected by LHON. Furthermore, we are actively exploring other indications where gene therapy may offer significant therapeutic benefit in the hope of meeting more unmet clinical needs.”

Neurophth’s most advanced investigational gene therapy is NR082 (rAAV2-ND4), which is currently being evaluated in separate clinical trials in the US (NCT05293626) and China (NCT04912843) for the treatment of LHON associated with mitochondrial ND4 mutations. 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

“Neurophth has accumulated a wealth of experience through long-term research,” Li said in a statement at the time of the NMPA’s IND clearance for NFS-02.3 “In March, a Maltese patient came to China to find NFS-02 and participated in the investigator-initiated trial, as it’s currently the only gene therapy for ND1-LHON. We will continue to execute our patient-first evaluation in the future.”

1. Neurophth announces first patient dosed in phase I/II clinical trial of second gene therapy. News release. Neurophth Therapeutics, Inc. August 17, 2023. Accessed August 23, 2023.
2. Neurophth receives IND clearance from FDA for AAV-ND1 gene therapy of LHON. News release. Neurophth Therapeutics, Inc. December 19, 2022. Accessed August 23, 2023.
3. Maltese patient received world's first ND1-LHON gene therapy injection donated by Neurophth in China. News release. Neurophth Therapeutics, Inc. March 8, 2023. Accessed August 23, 2023.
4. Neurophth announces IND approval by the NMPA for second gene therapy NFS-02 (rAAV2-ND1). News release. Neurophth Therapeutics, Inc. April 15, 2023. Accessed August 23, 2023.
5. Neurophth Therapeutics. Pipelines. Website Accessed December 21, 2022.
Recent Videos
Leigh Ramos-Platt, MD, on Looking Forward to Gene Therapy’s Growth
Jacques Galipeau, MD, on Highlights from ISCT 2024’s Presidential Plenary
Zheng-Yi Chen, DPhil, on International Collaboration on Clinical Trials
Shankar Ramaswamy, MD, the cofounder, chairman, and CEO of Kriya Therapeutics
Zheng-Yi Chen, DPhil, on Looking Deeper Into Effects of Gene Therapy on OTOF Deafness
Arshad Khanani, MD
Alfonso Sabater, MD, PhD
Shankar Musunuri, PhD
Ula V. Jurkunas, MD
Alfonso Sabater, MD, PhD, on Bringing Gene Therapy to Ophthalmology
© 2024 MJH Life Sciences

All rights reserved.