Neurophth Biotechnology Ltd, a fully-integrated genomic medicines company developing adeno-associated viral (AAV)-delivered gene therapies for the treatment of ocular diseases, announced that the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) has approved the company's Investigational New Drug (IND) application of NR082 (recombinant adeno-associated virus serotype 2 carrying ND4 gene; rAAV2-ND4) for Leber hereditary optic neuropathy (LHON) patients with ND4 mutations.
It marks the first AAV2 gene therapy IND application approval in China. Previously, the company announced NR082 has granted orphan drug designation by the US FDA in September 2020.
The CDE of China NMPA-approved clinical trial is a multicenter, open-labeled, single-arm study investigating the safety and efficacy of NR082 in LHON patients with ND4 mutations. Investigational NR082, a novel recombinant adeno-associated viral serotype 2 (rAAV2) containing a codon-optimized of NADH-dehydrogenase subunit 4 (ND4) gene under the control of the cytomegalovirus promoter and enhancer, is a novel ophthalmic injection that is being developed for the treatment of LHON associated with ND4 mutations.
The team of Professor Bin Li, founder and chairman of Neurophth, has started the research and exploration of ophthalmic gene therapy technology since 2008 and launched the world's first investigator-initiated trial (IIT-1) of LHON gene therapy in 2011. Between 2017 and 2018, the team also completed the enrollment of an international multicenter clinical trial (IIT-2) of LHON gene therapy with the largest sample size in the world. Safety, efficacy and clinical durability up to 90 months of LHON gene therapy have been demonstrated in these two investigator-initiated trials (IITs). The results of these two studies of 168 LHON patients demonstrated that an intravitreal injection of rAAV2-ND4 in LHON patients is well tolerated and can be effective at improving visual acuity, which provides favorable support for the industrial development of LHON candidate drugs.
"We are extremely pleased that the NMPA has granted permission to proceed with this clinical study. This is a big step toward a potential therapy for the LHON community. It has been a long journey since the team started supporting this promising gene therapy research over a decade ago. We are thrilled that it is now entering the clinic, bringing tremendous hope to families and the entire LHON community. I'd like to thank the team involved for their continued support," said Prof. Bin Li.
Dr. Alvin Luk, CEO of Neurophth, added, "NR082 is the first AAV ocular gene therapy to enter active clinical development in China. The program captures the essence of our mission – to liberate patients from debilitating ophthalmic diseases by rapidly advancing the in-vivo gene therapy programmes into clinical development. We look forward to working with our study investigators, regulatory agency, the patient community, and families to get the clinical trial underway, the first of 10 gene therapy products currently under development at Neurophth
