MeiraGTx Announces Positive Clinical Data of Investigational Gene Therapy for X-Linked Retinitis Pigmentosa
MeiraGTx Holdings announced 6-month data from the ongoing phase 1/2 clinical trial of AAV-RPGR, an investigational gene therapy in development for the treatment of patients with X-linked retinitis pigmentosa (XLRP) with genetically confirmed variants in the RPGR gene. Significant improvement in vision was demonstrated in the dose escalation phase of the trial and AAV-RPGR was found to be generally well tolerated, according to MeiraGTx.
These initial results from the trial are being presented as a late-breaker oral presentation at the American Society of Retina Specialists (ASRS) 2020 Virtual Annual Meeting.
MeiraGTx and Janssen Pharmaceuticals are jointly developing AAV-RPGR as part of a broader collaboration to develop and commercialize gene therapies for the treatment of inherited retinal diseases.
The ongoing phase 1/2 MGT009 clinical trial consists of three phases: dose-escalation, dose-confirmation, and dose-expansion. In the dose-escalation phase (n=10), adults were administered low, intermediate, or high dose AAV-RPGR. Each patient was treated with subretinal delivery of AAV-RPGR in the eye that was more affected at baseline. The patient’s other eye served as an untreated control. The primary endpoint of the trial is safety, with secondary endpoints assessing changes in visual function at prespecified timepoints post-treatment. Baseline values were determined in triplicate.
At 6 months, significant improvement in retinal sensitivity was demonstrated in patients treated with low and intermediate dose AAV-RPGR. Improvement was evident at first post-treatment perimetry assessments at 3 months, with improvements generally sustained or increased at 6 months. Significant differences were observed in retinal sensitivity between treated and untreated eyes over time. Based on the robust safety and efficacy signals observed in the dose escalation portion of the study, the low and intermediate doses were selected for use in the ongoing randomized, controlled dose-expansion phase of the trial.
“XLRP is characterized by early-onset visual field loss, with most patients progressing to blindness and associated loss of independence by young adulthood,” Michel Michaelides, BSc, MB, BS, MD(Res), FRCOphth, FACS, MGT009 trial investigator, Consultant Ophthalmologist, Moorfields Eye Hospital and Professor of Ophthalmology, University College London, said in a company news release. “Six-month data demonstrate AAV-RPGR may improve visual function in XLRP patients. Initial data also suggest treatment with AAV-RPGR has the potential to stabilize or slow progressive vision loss. These results support AAV-RPGR as an important advancement in the treatment of XLRP, for which there is no currently available therapeutic option.”
Based on the encouraging safety and efficacy data demonstrated in the MGT009 trial to date, MeiraGTx and Janssen expect to advance AAV-RPGR into the phase 3 Lumeos clinical trial for the treatment of patients with XLRP caused by mutations in RPGR gene.
“We are pleased to share these encouraging initial results from our XLRP gene therapy trial and look forward to advancing this program into a phase 3 trial,” Alexandria Forbes, PhD, president and chief executive officer of MeiraGTx, said in the news release. “These early data suggest AAV-RPGR has the potential to address some of the key functional manifestations of this severe disease for which there is no currently available therapy. I’d like to thank the investigators, patients and families who dedicate their time to our clinical trials and who continue to support us in our efforts to develop therapies that have the potential to make a meaningful difference and improve the lives of people with serious diseases.”
Data Summary:
Data obtained to date suggest AAV-RPGR is generally well-tolerated. Most adverse events (AEs) were related to the surgical delivery procedure, were transient and resolved without intervention. There were no dose-limiting events. Inflammatory responses to therapy were observed in two out of three patients in the high dose cohort, which may have been associated with decreased activity of AAV-RPGR in these patients. Inflammation was effectively managed with an extended steroid protocol.
Six-month data from the dose escalation portion of the study (n=10) demonstrated meaningful improvement from baseline in retinal sensitivity in the low (n=3) and intermediate (n=4) dose cohorts. Importantly, these improvements were evident when assessed with two perimetry approaches (static perimetry and microperimetry) and three analysis metrics (mean retinal sensitivity, central 30° hill-of-vision volumetric measure (V30), and pointwise comparison).
- Significant differences in mean retinal sensitivity were observed between treated eyes and untreated eyes in the intermediate dose cohort: 1.02 dB (90% CI: 0.75, 1.31)
- Significant differences were observed in central visual field progression rate (V30) between treated eyes and untreated eyes in both the low2, 1.10 dB-sr/year (90% CI: 0.10, 2.10) and intermediate, 1.26 dB-sr/year (90% CI: 0.65, 1.86), dose cohorts.
- Efficacy signals were observed at first post-treatment assessments at three months, with improvements generally sustained or increased at six months.
ASRS Presentation Information:
Late-Breaker Presentation
Title: AAV-RPGR Gene Therapy for RPGR-Associated X-Linked Retinitis Pigmentosa: 6-month Results From a Phase 1/2 Clinical Trial
Presenter: Michel Michaelides, UCL Institute of Ophthalmology; Moorfields Eye Hospital
Date: Oral presentation available to ASRS meeting attendees on the virtual meeting site as of July 17, 2020; live Q&A session to take place July 25, 2020
Session: Hereditary Retinal Diseases Symposium
Time: 11:55 a.m. – 12:10 p.m. ET