Neurophth Announces Clinical Advancement of Two Ophthalmic Gene Therapies: NR082 Receives U.S. IND Approval and NFS-02 Granted FDA Orphan Drug Designation

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Recently, two ophthalmic in vivo gene therapy drugs under development by Neurophth have made new progress: NR082 has been approved for clinical trials in the United States, targeting Leber's Hereditary Optic Neuropathy (LHON) caused by ND4 mutations; NFS-02 has been granted Orphan Drug Designation by the US FDA for the treatment of LHON caused by ND1 mutations.

According to the introduction on the Neurophth Biotechnology's official website, Leber hereditary optic neuropathy (LHON) is a rare maternally inherited mitochondrial disease that causes bilateral vision loss leading to blindness. More than 90% of LHON cases are caused by three mitochondrial DNA mutations: G11778A (ND4 gene), G3460A (ND1 gene), and T14484C (ND6 gene), with the G11778A mutation in the ND4 gene being the most common. These genetic mutations impair the function of the mitochondrial respiratory chain in cells, resulting in reduced ATP production, oxidative stress in retinal ganglion cells, and ultimately leading to cell apoptosis. Currently, there is no effective treatment or cure available for LHON in clinical practice, indicating a significant unmet medical need.

Public information shows that NR082 (NFS-01), the first candidate drug developed by Neurophth, is currently undergoing a multi-center, 1/2/3 phase two-stage clinical study targeting Chinese patients with Leber's hereditary optic neuropathy (LHON) caused by ND4 mutations. It uses recombinant adeno-associated virus serotype 2 (rAAV2) to deliver a bioengineered ND4 gene, and through a single intravitreal injection, delivers the correct ND4 protein to the optic nerve cells of LHON patients, thereby improving or even restoring severe vision loss caused by ND4 mutations.

According to an earlier press release from Neurophth, the safety and efficacy of NR082 have been demonstrated in three investigator-initiated clinical studies (IITs) involving 186 subjects with Leber's hereditary optic neuropathy. Long-term safety, efficacy, and tolerability in some patients have even reached up to 90 months.

Previously, NR082 has been granted Orphan Drug Designation by the FDA for the treatment of Leber's Hereditary Optic Neuropathy (LHON) caused by ND4 mutations. This time, the product has been approved in the United States to conduct a multi-center, open-label, single-arm clinical study, which will evaluate the safety and efficacy of NR082 in patients with LHON caused by ND4 mutations.

Public information shows that NFS-02 (rAAV2-ND1) is also an ophthalmic in vivo gene therapy drug under development. It is the second candidate drug of Neurophth to obtain FDA orphan drug designation and is currently being developed for the treatment of Leber's hereditary optic neuropathy caused by ND1 gene mutations. It is in the preparation stage for IND application.

According to the introduction on the Neurophth website, NFS-02 is similar to NR082 in terms of mechanism of action. It adopts a gene therapy strategy, using recombinant adeno-associated virus as a vector to deliver the correct gene to the patient's damaged retinal ganglion cells via intravitreal injection, repairing the mitochondrial bio-respiratory chain and restoring vitality and visual function to the retinal ganglion cells.

References:

[1] First Chinese-produced ophthalmic gene therapy drug receives U.S. FDA clinical trial approval. Retrieved Jan 18, 2022, from https://www.neurophth.com/NewsD-271.html

[2] First Case in China! Neurophth Announces the First Patient Dosed in the Registrational Clinical Trial of the First In Vivo Gene Therapy for Ophthalmology LHON. Retrieved Jun 28, 2021, from https://www.neurophth.com/NewsD-241.html

[3]NFS-02! Neurophth's New In Vivo Gene Therapy for Ophthalmology Receives FDA Orphan Drug Designation. Retrieved Jan 19, 2022, from https://mp.weixin.qq.com/s/fUCJ_ye4Ep8MMVStTYOckg

(Original text has been edited)

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