Phase 1/2  study of AAV5-RPGR gene therapy for RPGR-associated X-Linked Retinitis Pigmentosa present preliminary results

Researchers based at UCL Institute of Ophthalmology and Moorfields Eye Hospital, London UK, have presented preliminary data results on X-linked retinitis pigmentosa (XLRP) at the EURETINA 2021 Virtual Conference, September 9-12th.  The clinical researchers presented retinal sensitivity data, measured by perimetry, following on from 10 XLRP participants treating a gene therapy strategy using AAV-RPGR.  The results demonstrated positive retinal sensitivity outcomes, including V30 measurement, indicating an improvement of “reversing a downward trajectory”, for treated vs untreated eyes.   The current study uses an open-label Phase I/II dose-escalation trial to determine the safety and efficacy of subretinal administration of AAV2/5 vector in participants with XLRP caused by mutations in RPGR (Retinitis Pigmentosa GTPase Regulator).


X-linked RP is one of the most common forms of retinitis pigmentosa and mutations in one gene, the RP GTPase regulator gene (RPGR gene), are thought to account for approximately 75% of XLRP recorded cases.  Males are obviously more severely affected by the X-linked pathology with night blindness generally occurring within the first decade of life, followed by restriction of the visual field and loss of visual acuity leading to legal blindness in most patients by the fourth to fifth decade of life.  AAV5-RPGR provides an investigational gene therapy for the treatment of patients with XLRP caused by disease-causing variants of the RPGR gene (RPGR ORF15). The experimental treatment is designed to deliver functional copies of the RPGR gene to the subretinal space in order to improve and preserve vision.  Results of the recent study at the EURETINA 2021 Conference (Virtual) showed that the AAV-RPGR treatment (“MGT009”) recruited 10 males applying a dose escalation study for low, intermediate and high titres. The low, intermediate and high doses reported baseline characteristics for mean visual acuity (VA, letters, range) had a low dose (n=3), VA 62(52, 70), intermediate dose 72 (60,77), and a higher dose for 73 (59,83).  Following treatment, at the 12 month time-point post-intervention showed that treatment “with low and intermediate doses of AAV-RPGR resulted in clinically meaningful improvements in retinal sensitivity across multiple metrics and modalities”.  According to the UK researchers, the two doses, low and intermediate, are now “being further explored in a randomized controlled Phase 3 clinical trial (NCT04671433)”, recruiting up to 60 patients aiming to complete the study by end of H2-FY2022.


The lead author  of the study, Dr. Michel Michaelides, UCL and Moorfields, presented the data at the EURETINA 2021 conference.  Commenting on the optimism for building gene therapy data for multiple international research groups, Dr. Michaelides, stated that, “I certainly tell patients that I am optimistic that there will be treatments that will come their way in a meaningful time.  I used to previously say I was cautiously optimistic, but I’ve dropped the cautious aspect because I do believe there are just so many good, well-designed therapies and trials underway”.  The AAV-RPGR initiative will also be supported by MeiraGTx as the Sponsor, conducting 5 clinical sites across the UK and US (Massachusetts Eye and Ear Institute, Boston; Kellogg Eye CenterAnn Arbor, Michigan; UPMC Eye Center, Pittsburgh, Pennsylvania; Leeds Teaching Hospitals NHS Trust, UK and Moorfields Eye Hospital NHS Foundation Trust, London, UK.