1. Jul 20, 2020

Interim 6-month data of RPGR gene therapy shows significant vision improvement in patients living with X-linked retinitis pigmentosa

The Janssen Pharmaceutical Companies of Johnson & Johnson announced 6-month data from the ongoing phase 1/2 trial of its investigational gene therapy for the treatment of inherited retinal disease X-linked retinitis pigmentosa (XLRP). 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. Initial data on the novel AAV-RPGR asset, jointly developed with MeiraGTx Holdings, will be available today as a late-breaker, pre-recorded oral presentation at the American Society of Retina Specialists (ASRS) 2020 Virtual Annual Meeting.

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.

“There is an urgent need to deliver a transformational therapy for people living with XLRP who experience progressive visual loss from childhood with eventual blindness in early adulthood,” said Michel Michaelides, BSc, MB, BS, MD (Res), FRCOphth, FACS, trial investigator, Consultant Ophthalmologist, Moorfields Eye Hospital, Professor of Ophthalmology, University College London. “We have learned valuable safety and efficacy information from this phase 1/2 trial and look forward to applying those learnings in our next phase of study.”

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 prespecified timepoints post-treatment. Baseline values were determined in triplicate.

In the dose escalation phase, at 6 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:

  • Significant differences in mean retinal sensitivity were observed between treated and untreated eyes in the intermediate dose cohort: 1.02 decibel (dB); (90% CI: 0.75, 1.31).
  • Significant differences were observed in central visual field progression rate (V30) between treated and untreated eyes in the low: 1.10 dB-sr (steradian)/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 6 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,” James List, MD, PhD, 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.”

“With patient needs setting our priorities, Janssen is committed to investing in our retinal portfolio and working tirelessly to bring transformational therapies to patients worldwide,” said Mathai Mammen, MD, PhD, Global Head, Janssen Research & Development, Johnson & Johnson. “These new data highlight our progress to advance this clinical program and support further study of our investigational gene therapy.”

Johnson & Johnson’s pre-recorded webcast, which reviews interim data from the hase 1/2 RPGR clinical trial and Janssen’s retinal portfolio strategy, features James List, MD, PhD, Global Therapeutic Area Head, Cardiovascular & Metabolism, Janssen Research & Development, LLC, and can be accessed on the Johnson & Johnson website at www.investor.jnj.com by clicking on “Webcasts/Presentations”. The webcast is approximately 10 minutes and will be available through the end of August 2020. ASRS will also host a live Q&A session on July 25, 2020 from 11:55AM–12:05PM (ET) for registered meeting participants.

Source: Johnson & Johnson