Interim data from an ongoing Phase 1/2 trial showed vision improvement for the investigational gene therapy for the treatment of inherited retinal disease X-linked retinitis pigmentosa (XLRP). This announcement of six-month data for the trial NCT03252847 comes from the Janssen Pharmaceutical Companies of Johnson & Johnson.
The interim data showed that low and intermediate doses of the investigational adeno-associated virus retinitis pigmentosa GTPase regulator (AAV-RPGR) were generally well-tolerated and indicated significant improvement in vision. The Initial data on the novel AAV-RPGR asset was jointly developed with MeiraGTx Holdings plc.
In patients with XLRP, the photoreceptors in the eye that are responsible for converting light into signals that are sent to the brain function poorly, leading to degeneration of the retina and legal blindness in adulthood. The companies’ AAV-RPGR gene therapy is being investigated to treat the most common and severe forms of XLRP caused by mutations in the RPGR gene by preserving and improving vision and slowing retinal degeneration. Currently, there are no approved treatments for this condition.
The ongoing Phase 1/2 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. The primary endpoint of the trial is safety, with secondary endpoints assessing changes in visual function at pre-specified timepoints post-treatment. Baseline values were determined in triplicate.
In the dose escalation phase, at six months, the low (n=3) and intermediate (n=4) dose cohorts demonstrated significant improvement from baseline in retinal sensitivity after treatment. 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). These interim results from the Phase 1/2 trial participants suggest that the findings are significant:
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Significant differences in mean retinal sensitivity were observed between treated and untreated eyes in the intermediate dose cohort.
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Significant differences were observed in central visual field progression rate (V30) between treated and untreated eyes in the low dose cohort.
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Efficacy signals were observed at first post-treatment assessments at three months with improvements generally sustained or increased at six months.
Perimetry is a sensitive standard-of-care measure of retinal function that reproducibly determines retinal sensitivity both cross-sectionally and longitudinally, thereby accurately defining disease progression over time.
Safety data obtained to date has ocular and systemic safety profiles that are anticipated and manageable. The most common adverse events were related to the surgical procedure, transient and resolved without intervention. In the high dose cohort (n=3), inflammation was evident in two of three adults and measures of visual function were not improved.
“These findings demonstrate the potential of our investigational AAV-RPGR gene therapy not just to preserve, but improve vision for people living with XLRP,” said James List, M.D., Ph.D., Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC. “We are encouraged by the data we have seen to date, and look forward to sharing future read-outs and advancing our clinical development program.”
About the Phase 1/2 RPGR Trial (MGT009) and AAV-RPGR
MGT009 (NCT03252847) is an open-label, multi-center, dose-escalation trial, which enrolled patients aged five years and older with XLRP caused by mutations in RPGR at multiple sites in the United States and United Kingdom. The primary endpoint was safety and tolerability; secondary endpoints assessed retinal sensitivity, visual function, functional vision and quality of life measurements.
AAV-RPGR was delivered via subretinal injection targeting the central retina in the eye that was more affected at baseline. The patient’s other eye served as an untreated control. Multiple retinotomies were permitted to enable coverage of the largest possible area of rescuable retina. Perimetry was performed using Octopus 900 full-field static perimetry and MAIA fundus-guided microperimetry, and was conducted at baseline, three, six, nine and 12 months to assess baseline retinal function and change over time. For more information, visit: https://clinicaltrials.gov/ct2/show/NCT03252847?
About the Janssen and MeiraGTx Strategic Collaboration
In January 2019, Janssen entered into a worldwide collaboration and license agreement with MeiraGTx Holdings plc, a clinical-stage gene therapy company, to develop, manufacture and commercialize its clinical-stage inherited retinal disease portfolio. AAV-RPGR gene therapy is being developed under this collaboration and license agreement. In addition to forming a research collaboration to explore new targets for other inherited retinal diseases, Janssen is working with MeiraGTx to build core capabilities in viral vector design, optimization and manufacturing.
Full press release from Janssen.