MeiraGTx Presents Clinical Data on Botaretigene Sparoparvovec for the Treatment of X-Linked Retinitis Pigmentosa at the ARVO 2022 Annual Meeting

MeiraGTx Holdings plc announced that additional clinical data from the phase 1/2 trial of botaretigene sparoparvovec for the treatment of x-linked retinitis pigmentosa (XLRP) were presented at the Association for Research in Vision and Ophthalmology (ARVO) 2022 Annual Meeting in Denver, Colorado by Professor Michel Michaelides. A poster presentation of human retinal organoid vector efficacy data was also delivered at the conference.
 
Oral Presentation Details:
Abstract Title: AAV5-RPGR (botaretigene sparoparvovec) Gene Therapy for X-linked Retinitis Pigmentosa (XLRP) Demonstrates Localized Improvements in Static Perimetry
Presenter: Dr. Michel Michaelides, Professor of Ophthalmology, UCL Institute of Ophthalmology in Dept. of Genetics
Patients in the multicenter, open-label phase 1/2 trial were given botaretigene sparoparvovec subretinally at 1 of 3 doses to the worse-seeing eye. Changes in retinal sensitivity and the volumetric analysis of the central 30 degrees of the retinal field were examined and compared to the untreated surrounding area as well as the retina of the untreated fellow eye. Exploration of the association between the location of botaretigene sparoparvovec delivery and changes in retinal sensitivity was undertaken by overlaying bleb topography onto sensitivity heat maps. Data from the study indicates improvements in photoreceptor function assessed through 12 months post-treatment suggesting local efficacy of botaretigene sparoparvovec gene therapy in XLRP patients. The treatment effect is observed within the treated bleb and may also extend beyond the margins of the bleb following surgery owing to subretinal extension before retinal reattachment.
 
Poster Presentation Details:
Abstract Title: AAV-RPGR Gene Therapy for RPGR-Associated X-Linked Retinitis Pigmentosa (XLRP): Human retinal organoid vector efficacy data
Presenting Author: Paul E. Sladen
Mutations within the retinitis pigmentosa GTPase regulator (RPGR) are the most frequent cause of XLRP. This study investigated the efficacy of RPGRORF15 gene supplementation in human RPGR-deficient retinal organoids (ROs). Successful differentiation of RPGR-KO iPSCs was confirmed by qPCR and immunocytochemistry of major retinal and phototransduction markers. Viral transduction of RPGR-KO ROs with AAV-RPGR led to restoration of RPGR expression in human rods and cones. RPGR was localized at the photoreceptor cilium and led to marked improvements in several molecular, phenotypic readouts. The RPGR transgene was correctly expressed, processed, and localized in human rods and cones following viral transduction of RPGR-deficient human ROs. These data are consistent with the reported Phase 1/2 trial positive results for botaretigene sparoparvovec in patients with RPGR-associated XLRP.
 
MeiraGTx and Janssen Pharmaceuticals, Inc., part of the Janssen Pharmaceutical Companies of Johnson & Johnson, are jointly developing botaretigene sparoparvovec as part of a broader collaboration to develop and commercialize gene therapies for the treatment of inherited retinal diseases. MeiraGTx remains eligible to receive additional development and commercial milestones for botaretigene sparoparvovec as well as for other programs as part of the collaboration agreement.