New Medicines

Leber congential amaurosis caused by mutations in the RPE65 gene


New molecular entity

Development and Regulatory status

Phase II Clinical Trials
Phase II Clinical Trials
Nov 21MeiraGTx plans to initiate a Phase 3 pivotal trial of AAV-RPE65 for patients with RPE65-associated retinal dystrophy in early 2022 [7].
Apr 19Has orphan drug status in EU & US [3].
Dec 17Granted rare paediatric disease designation in the US [3].


An in vivo adeno-associated virus (AAV) gene therapy (serotype 5) containing the human RPE65 gene
LCA is the severest of all retinal dystrophies. Affected individuals usually present in the first year of life with profound sight impairment, roving nystagmus, variable retinal pathology and occasionally other systemic pathology. It is known to be caused by at least six genes. Estimated prevalence is 1 per 50,000-100,000 [1].
Leber congential amaurosis caused by mutations in the RPE65 gene
Subretinal injection

Trial or other data

Mar 21Long-term PI/II follow-up trial (NCT02946879) is recruiting and due to complete collection of primary outcome data in Apr 23 [8].
Mar 20In its 2019 annual report, MeiraGTx provides an update on the PI/II OPTIRPE65 trial. Dosing was completed in Jun 18. The primary endpoint was safety. Secondary endpoints included the outcomes of a range of functional tests, detailed structural analysis of the retina and quality of life measures. A total of 15 patients were treated in this clinical trial, including nine adult patients in three dose escalation cohorts and six paediatric patients in the pediatric extension arm of the trial. In May 2019, positive topline safety and efficacy data were announced. Additional data from this study were presented at the Retina Subspecialty Day of the American Academy of Ophthalmology Annual Meeting in Oct 19. AAV-RPE65 met the primary endpoint of safety and tolerability. Additionally, AAV-RPE65 demonstrated statistically significant improvement across several secondary endpoints assessing clinical activity. Significant improvement in vision was demonstrated at six months after AAV-RPE65 treatment, as measured by assessments of visionguided mobility, retinal sensitivity, visual acuity and contrast sensitivity. Larger improvements from baseline in functional vision were observed between treated and control eyes at lower light levels [6].
Dec 19UK trial sites: NCT02781480 and NCT02946879 - Moorfields
Dec 17PI/II trials (NCT02781480 & NCT02946879) are recruiting [2].
Nov 16Long-term follow-up study of patients following the PI/II dose escalation trial starts (MGT004; NCT02946879). This open label trial will enrol approximately 27 patients in the UK [2].
Apr 16MeiraGTx and Medical Research Council, in collaboration with University college of London, starts a PI/II OPTIRPE65 trial of A001 for gene therapy of adults and children with retinal dystrophy associated with defects in RPE65 (Leber congenital amaurosis) (MGT003; NCT02781480). This open-label, dose-escalation trial intends to enrol approximately 27 patients in the UK and US [2].