LHON-ND4 Gene Therapy Trial Completes Enrollment

NR082 is being evaluated in a phase 1/2/3 clinical trial in patients with Leber hereditary optical neuropathy.

Neurophth has completed patient enrollment in its phase 1/2/3 clinical trial (NCT04912843) evaluating its gene therapy NR082 for the treatment of Leber hereditary optic neuropathy (LHON) with ND4 mutations.1

"We are extremely excited to announce the completion of the last patient visit in this phase 3 study, which marks a significant advancement for NR082 as well as a minor step toward the commercialization of China's self-developed ocular gene therapy. It often takes a decade to develop an innovative drug, and Chinese ophthalmic gene therapy drug costs much more than that,” Prof. Bin Li, founder, chairman and chief executive officer,Neurophth, said in a statement.1 "We would like to express our gratitude to all clinical investigators, trial participants and their families for their time and commitment, and also the excellent teamwork of the entire company to complete the phase 3 clinical trial within 5 months. We are confident that the company will live up to our promise to commercialize Chinese in vivo gene therapy soon and make it available to patients."

NR082 uses a recombinant adeno-associated virus vector (rAAV2) that contains anoptimized ND4 gene under the control of the cytomegalovirus promoter and enhancer to deliver the corrected gene to the patients' damaged optic ganglion cells through intravitreal injection. It is designed to repair the mitochondrial biological respiratory chain and restore damaged optic ganglion cells.

NR082 is being evaluated in a multi-center, 2-part study inparticipants between the ages of 18 and 75 years. Part 1 is a safety, dose-finding phase 1/2 study and part 2 will evaluate the recommended phase 2 dose (RP2D) for efficacy in a randomized, double-blind, controlled phase 3 study. Six patients will be enrolled in the safety run-in phase in part 2 and the randomized portion will begin 6 weeks later pending any new safety signals and Safety Review Committee decision.

READ MORE: Gene Therapy Continues to be Well-Tolerated in Retinitis Pigmentosa

Participants will receive 0.5E9 viral genomes (vg), 1.5E9 vg, or 4.5E9 vg in 1 eye during part 1. In part 2, participants will receive the RP2D in 1 eye and a sham injection in the other. Part 2 primary outcome measures include safety as measured by adverse event (AE) incidence within 6 weeks and efficacy as measured by best corrected visual acuity at 52 weeks. Secondary measures include immunogenicity and vector shedding/biodistribution, cell immunity, humoral immunity, vector DNA shedding in tears (both eyes), biodistribution in whole blood, change in quality of life, change in VFQ-25 and SF-36, and morphological improvement as measured by Retinal Nerve Fiber Layer, ganglion cell layer, and inner plexiform layer thickness in the study eye.

"The design of the NR082 clinical trial and the selection of the optimal dose were based on multiple successful previous studies and in accordance with the CDE. Neurophth and CRO collaborated closely to overcome the challenges of COVID-19 and complete the enrollment of all patients successfully,” Xiaoning Guo, PhD, chief medical officer, Neurophth, added to the statement.1 "We are optimistic about the outcome of this clinical trial. If the study meets the pre-defined endpoints, we will submit a New Drug Application as soon as possible for the early launch of NR082 in China and in the meantime, advance the progress of clinical trial in the U.S. to offer a direly needed treatment for LHON patients."

Another of Neurophth’s pipeline candidates, NFS-02, received investigational new drug application clearance to treat LHON with ND1 mutations in December 2022.2 The company will soon initiate a phase 1/2 trial to evaluate the rAAV2-ND1 gene therapy.

1. Commercialization of gene therapy is coming soon: Neurophth completes patient enrollment for phase iii clinical trial for the gene therapy treatment of LHON. News release. Neurophth. February 21, 2023. https://finance.yahoo.com/news/commercialization-gene-therapy-coming-soon-133000545.html
2. Neurophth receives IND clearance from FDA for AAV-ND1 gene therapy of LHON. News release. Neurophth. December 19, 2022. https://www.neurophth.com/en/NewsD-365.html
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