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Neurophth Therapeutics' Treatment of Leber's Hereditary Optic Neuropathy Gene Therapy NR082 was Granted Orphan Drug Designation by EMA

Neurophth Therapeutics' Treatment of Leber's Hereditary Optic Neuropathy Gene Therapy NR082 was Granted Orphan Drug Designation by EMA

WUHAN, China and SAN DIEGO, Jan. 25, 2022 /PRNewswire/ -- Neurophth Therapeutics, Inc., (hereinafter referred to as "Neurophth"), today announced that the European Medicines Agency (EMA) Committee for Orphan Medicinal Products (COMP) granted the orphan drug designation (ODD) for the Company's leading gene therapy drug candidate, NR082 (rAAV2-ND4), for the treatment of Leber's hereditary optic neuropathy (LHON) associated with mtND4 mutation. Please see Public Summary of the COMP opinion on EMA website Union Register of medicinal products - Public Health - European Commission (

"The positive opinion from the COMP acknowledges the compelling IND-enabling data and clinical data of 186 subjects from three investigator-initiated trials (IITs)," said Dr. Bin Li, Founder of Neurophth. "Some of the subjects in the earlier IIT were followed for up to 75-90 months, demonstrating excellent clinical durability. Our integrated Phase 1/2/3 registrational trial is ongoing, and the data from this trial are intended to support global regulatory filings."

"This orphan drug designation is an important milestone toward addressing the unmet need of families and patients living with LHON, and it follows the ODD previously granted in 2020 by the US. Food and Drug Administration (FDA) for this same gene therapy drug candidate as a potential treatment for mtND4-LHON," said Xin Zhang, M.D., M.Sc., Chief Medical Officer and Chief Operations Officer at Neurophth. "In China, for Global - as Neurophth expands its regulatory strategy in Europe, we will continue to make meaningful changes in the lives of patients with genetic diseases around the world."

Ms. Yiyuan Chen, Head of Global Regulatory Affairs of Neurophth, commented, "We are very pleased to receive EMA's orphan drug designation, which is another good news following the recent US IND clearance of NR082 and the grant of US Orphan Drug Designation of NFS-02. This is a true reflection of the company's operational excellence. We will continue to deliver our promise to bring transformative treatments to patients around the world."

About Orphan Drug Designation

EMA orphan designation is designed to encourage the development of new treatments to treat a seriously debilitating or life-threatening condition that affects fewer than 5 in 10,000 people in the European Union (EU), and there must be sufficient non-clinical or clinical data to suggest the investigational medicine may produce clinically relevant outcomes. Medicines that meet the EMA's orphan designation criteria qualify for several incentives, including 10 years of market exclusivity, clinical protocol assistance, differentiated evaluation procedures for Health Technology Assessments in certain countries, access to a centralized marketing authorization procedure valid in all EU member states, and potentially reduced fees for regulatory activities. Applications for orphan designation are examined by the EMA's Committee for Orphan Medicinal Products (COMP), using the Committee's network of experts.

About Leber's Hereditary Optic Neuropathy (LHON)

Leber hereditary optic neuropathy (LHON) is a maternally inherited blinding bilateral optic atrophy[1] with a prevalence of around 1 in 31,000 to 1 in 54,000 particularly in young adult males[2]. There are three mitochondrial DNA point mutations account for about over 90% of all LHON cases, namely, G3460A in ND1, G11778A in ND4 and T14484C in ND6, with G11778A mutation in NADH-dehydrogenase subunit 4 (ND4) gene causing a ND4 subunit arginine to be incorrectly replaced by a histidine and reducing the activity of NADH dehydrogenase by 50-80% as being the most common mutation worldwide[1,3,4]. These mutations affect complex I subunits of the mitochondrial respiratory chain, impairing mitochondrial function and increasing the production of reactive oxygen species. The retinal ganglion cells (RGCs) appear to be selectively vulnerable to mitochondrial dysfunction resulting in apoptotic cell death, optic nerve degeneration, and the development of optic atrophy[4]. Thus, the pathophysiology of LHON is characterized by selective loss of RGCs and their axons, which leads to rapidly progressive bilateral vision loss. The visual prognosis is poor, and most patients progress to vision worse than 20/200 within the first year after disease onset[3]. There is currently no approved effective treatment for LHON and the current treatment remains limited[5].

About NR082

Investigational NR082 (rAAV2-ND4), a novel recombinant adeno-associated viral vector, serotype 2, containing a mitochondria codon-optimized NADH-dehydrogenase subunit 4 (ND4) gene under the control of the cytomegalovirus promoter and enhancer, is a novel gene therapy product that is being developed for the treatment of Leber hereditary optic neuropathy (LHON) associated with mtND4 mutations. The U.S. Food and Drug Administration (FDA) granted orphan-disease designation to NR082 in September 2020[6]. Safety and efficacy of mtND4 gene therapy have been evaluated in three investigator-initiated trials (IITs) with clinical durability up to 90 months in the first IIT. The results of these three IITs of 186 LHON patients demonstrated that an intravitreal injection of rAAV2-ND4 in subjects with LHON is well tolerated and can be effective at improving visual acuity[7,8,9].

About Neurophth

Neurophth is China's first gene therapy company for ophthalmic diseases. With subsidiaries in China (Wuhan, Shanghai, and Suzhou) and US (San Diego, California), Neurophth, a fully-integrated company, is striving to discover and develop genomic medicines for patients suffering from genetic diseases globally. Our validated AAV platform, which has been published in Nature - Scientific Reports, Ophthalmology, and EBioMedicine, has successfully delivered proof-of-concept investigator-initiated trials data of 186 subjects with investigational gene therapies in the retina. Our most advanced investigational gene therapy drug candidate, NR082 (rAAV2-ND4), in development for the treatment of mtND4-mediated LHON, has been granted orphan drug designation (ODD) by the U.S. FDA, an integrated Phase 1/2/3 clinical trial has been initiated with the first patient dosed in June 2021 after the IND clearance by the China NMPA in March 2021, and US IND has recently been cleared by US FDA. The pipeline also includes mtND1-mediated LHON (the Company's 2nd US ODD), autosomal dominant optic atrophy, optic neuroprotection (e.g., glaucoma), vascular retinopathy (e.g., diabetic retinopathy), and five other preclinical candidates. Neurophth has scaled up in-house manufacturing capability in Suzhou facility utilizing single-use technologies to support future commercial demand. To learn more about us and our growing pipeline, visit


  1. Carelli V, Carbonell M, deCoo IF, et al. International consensus statement on the clinical and therapeutic management of Leber hereditary optic neuropathy. Journal of Neuroophthalmology, 2017; 37: 371-381.
  2. Meyerson C, Van Stavern G, Mcclelland C. Leber hereditary optic neuropathy: current perspectives. Clinical Ophthalmology, 2015; 9:1165-1176.
  3. Yu-Wai-Man P, Votruba M, Burte F, et al. A neurodegenerative perspective on mitochondrial optic neuropathies. Acta Neuropathology, 2016; 132: 789-806.
  4. Newman NJ, Lott MT, Wallace DC. The clinical characteristics of pedigrees of Leber's hereditary optic neuropathy with the 11778 mutation. American Journal of Ophthalmology, 1991; 111: 750-762.
  5. Jurkute N, Harvey J, Yu-Wai-Man P. Treatment strategies for Leber hereditary optic neuropathy. Current Opinion of Neurology, 2019; 32: 99-104.
  6. Press release from Neurophth.
  7. Wan X, Pei H, Zhao MJ, et al. Efficacy and safety of rAAV2-ND4 treatment for Leber's hereditary optic neuropathy. Scientific Report, 2016; 6:21587.
  8. Yang S, Ma SQ, Wan X, et al. Long-term outcomes of gene therapy for the treatment of Leber's hereditary optic neuropathy. EBioMedicine, 2016; 10:258-268.
  9. Yuan JJ, Zhang Y, Liu H, et al. Seven-year follow-up of gene therapy for Leber's hereditary optic neuropathy. Ophthalmology, 2020; 127(8): 1125-1127.
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