Neurophth Therapeutics announced that the first patient has been dosed in its phase 1/2 gene therapy clinical trial for the treatment of Leber hereditary optic neuropathy (LHON) caused by the ND1 mutation (ND1-LHON).
Talk about this company first.
As China’s first in-vivo gene therapy company for ophthalmic diseases—with subsidiaries located across China (Wuhan, Shanghai, and Suzhou) and in the United States (San Diego, California). Neurophth is focused on developing genomic diseases to treat genetic disease such as LHON, optic neuropathy, vascular retinopathy, and autosomal dominant optic atrophy (ADOA).
Click here for a look at its pipeline.
To note, the company’s validated adeno-associated virus (AAV) platform for ocular gene therapy incorporates in-house genetic engineering technology with an optimal vector design to minimize dosages.
Who’s the founder?
Neurophth Founder, Chairman, and CEO Bin Li, PhD, MD, has served as a clinician at The Eye Center at Sun Yat-sen University along with being a professor and chief physician in the Ophthalmology Department of Tongji Hospital of Huazhong University of Science and Technology. He collaborated with his colleagues at the Tongji Medical College in conjunction with other universities in Wuhan with the first investigator-initiated gene therapy study on LHON in 2011.
The team later launched another gene therapy trial (NCT03153293) in 2017—leading to an accumulation of the longest follow-up time and largest sample size of safety and efficacy data in the world.
Go on …
Both studies evaluated the safety and efficacy of Neurophth’s advanced investigational candidate, recombinant AAV2 (rAAV2)-ND4, a gene therapy vector that enables allotopic expression to deliver the wild-type ND4 protein to the mitochondria within retinal ganglion cells for LHON patients.
To note, the FDA previously granted rAAVD-ND4 orphan drug designation (ODD) and accepted its investigational new drug (IND) in 2022.
Now this gene therapy.
Neurophth is developing two candidates for ND1-LHON based on rAAV2-ND4: NFS-01 and NFS-02.
Both drug’s mechanism of action (MOA) includes operating as a gene therapy to use recombinant AAV as the vector in order to deliver the correct genes to a patient’s damaged retinal ganglion cells via intravitreal (IVT) injection.
What’s the goal?
Their goal is to repair the mitochondrial biological respiratory chain—and, as a result, restore the retinal ganglion cells’ visual function.
Now about this phase 1/2 study … which therapy is being evaluated?
That would be NFS-02. Also of interest: NFS-02’s IND application was approved by the FDA in December 2022.
Gotcha. Tell me about it.
The multi-region, single-arm, open-label, dose-finding study (NCT05820152) is assessing the safety, tolerability, and efficacy of NFS-02 in an estimated 18 patients (aged ≥ 18 and ≤ 75) across the U.S. and China.
How is it designed?
Patients will receive a single unilateral IVT injection of NFS-02 with a starting dose of 1.5×108 vg, 0.05 mL eye/dose.
Other potential doses will depend on any drug-related dose-limiting toxicity (DLT) events after 6 weeks and be performed after an additional 6 weeks each (for 52 weeks).
They include:
- 5.0×107 vg, 0.05 mL eye/dose (low dose)
- 5.0×108 vg, 0.05 mL eye/dose (intermediate dose)
- 1.5×109 vg, 0.05 mL/eye/dose (high dose)
What’s being measured?
The primary outcomes include any adverse events (AEs), serious AEs, and occurrence of dose-limiting toxicity (DLT) events after 52 weeks.
Secondary outcomes will be measured anywhere from Week 1 up to Week 260. See here for further details.
When can we expect data?
Per Clinical Trials, the study is slated to conclude in its primary phase by December 2024. Stay tuned for interim data in the meantime!