A004

Unassigned

New Medicines

X-linked retinitis pigmentosa (XLRP)

Information

New molecular entity
Janssen
Janssen

Development and Regulatory status

Phase II Clinical Trials
None
Phase II Clinical Trials
Yes
Yes
Nov 20 · MeiraGTx entered into a worldwide collaboration and license agreement with Janssen Pharmaceutical in 2019 to develop, manufacture and commercialise clinical stage inherited retinal disease portfolio, including candidates for achromatopsia (AAV-CNGB3 and AAV-CNGA3) and X-linked retinitis pigmentosa, AAV-RPGR. Janssen has agreed to fund all clinical development and commercialisation costs for these programs [13].
Oct 20 · Based on the safety and efficacy profile demonstrated to date, the low and intermediate doses are being evaluated in the ongoing randomszed, controlled expansion portion of the PI/II study, which completed enrolment in the H1 20. MeiraGTx and Janssen plan to advance AAV-RPGR into a PIII pivotal study, called the Lumeos trial [12].
Apr 20 · Analysts predict launch in 2024 with 20% chance of success [10].
Mar 20 · Granted PRIME and ATMP designations from EMA [6].
Jan 20 · Filings planned between 2020 and 2023 [8].
Nov 18 · Granted Fast Track and orphan designation from the US FDA and orphan designation from the EMA. [3,5]

Category

XLRP, caused by RPGR gene mutation, leads to poor rod and cone function, retinal degeneration and blindness. A single injection of AAV-RPGR gene therapy delivers correct gene into the retina to slow retinal degeneration and preserve visual function.[1,2]
The prevalence of RP is estimated at ~1 in 5,000 individuals. XLRP accounts for 6-10% of cases [3,4]. This means ~ 1000 people in England are likely to affected at on time but not all will be eligible for this.
X-linked retinitis pigmentosa (XLRP)
Sub-retinal injection
Parenteral

Trial or other data

Nov 20 · MeiraGTx announces 12-month data from the ongoing PII/II MGT009 trial (NCT03252847). Statistically significant vision improvement in the dose escalation phase of the trial was sustained one year after treatment. These data were presented today as a late-breaker oral presentation at the American Academy of Ophthalmology (AAO) 2020 Virtual Annual Meeting. At the 12-month analysis, compared to baseline, six out of seven patients in the low (n=3) and intermediate (n=4) dose cohorts demonstrated improvement or stability in retinal sensitivity in the treated eye. Statistically significant differences in mean retinal sensitivity were observed between treated and untreated eyes in the intermediate dose cohort: 1.05 dB; (90% CI: 0.81, 1.29). Statistically significant differences were observed in central visual field progression rate (V30) between treated and untreated eyes in the low: 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 the first post-treatment assessments at three months, with improvements sustained or increased at 12 months [14].
Nov 20 · PI/II MGT009 study has been recruiting at 3 sites in the US and 2 sites in the UK (Leeds Teaching Hospitals NHS Trust and Moorfields Eye Hospital NHS Foundation Trust, London). The long-term follow-up MGT010 study is recruiting at Moorfields [11].
Nov 20 · PI/II MGT009 study (NCT03252847) is due to complete collection of all outcome data [11].
Oct 20 · EURETINA Safety Data Summary: As previously presented, signs of inflammation were observed in two out of three patients in the high dose cohort, which may have been associated with decreased activity of the AAV-RPGR treatment in these patients. Inflammation was effectively managed with an extended steroid protocol [12].
Oct 20 · EURETINA Data Summary: XLRP is characterized by progressive deterioration of the visual field. Octopus 900 full-field static perimetry and MAIA microperimetry were employed to determine change in retinal sensitivity following intervention. 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. At the nine-month analysis (Octopus 900 static perimetry), compared to baseline: Six out of seven patients in the low (n=3) and intermediate (n=4) dose cohorts demonstrated improvement or stability in retinal sensitivity in the treated eye. Improvements in treated eyes compared to baseline were sustained or further improved compared to the six-month analysis in the low and intermediate dose cohorts In each of the low and intermediate dose cohorts, significant improvement was observed between treated and untreated eyes in retinal sensitivity. At the six-month timepoint, improvements in retinal sensitivity were not observed in the high dose cohort. Perimetry assessment was not carried out in the high dose cohort at the nine-month timepoint due to protocol revision implemented to align with the dose-expansion cohort assessment schedule. Static Perimetry: Treated-Untreated Eye Difference at Nine Months (90% CI adjusted for baseline.) Mean Retinal Sensitivity (dB) Low 0.85 (0.05, 1.63) Intermediate 1.02 (0.78, 1.25) Central 30° Hill-of-Vision (V30, dB-sr/y) Low 1.07 (0.19, 1.94) Intermediate 1.10 (0.46, 1.74). Excludes one patient with panuveitis in the low dose. Markedly impaired mobility in low illumination is a hallmark symptom of XLRP. As part of the study, patients completed a vision-guided mobility maze to assess their ability to navigate across a broad range of controlled light levels (1 lux = deep twilight, 4 lux = residential street lighting, 16 lux = twilight conditions, 64 lux = car park and 256 lux = office work). At nine-month analysis, compared to baseline: Five of six patients demonstrated improvement in walk time for the treated eye at lux levels 1, 4 or 16. Significant improvement was observed between treated and untreated eyes in the low and intermediate dose cohorts (n=6) at 1 lux, -16.1 seconds (90% CI: 9.91, 22.1) and 4 lux, -3.71 seconds (90% CI: 2.83, 4.96); with the greatest improvement at the lowest light level (1 lux). Vision-guided mobility assessment was not carried out in the high dose cohort at the nine-month timepoint due to protocol revision implemented to align with the dose-expansion cohort assessment schedule. Safety data obtained to date continue to suggest AAV-RPGR is well-tolerated. No dose-limiting events occurred [12].
Oct 20 · Nine-month data from the MGT009 study presented at EURETINA 2020. Data at the nine-month time point continued to demonstrate significant improvement in retinal sensitivity in treated eyes in both the low and intermediate dose cohorts. In addition, data from the assessment of vision-guided mobility carried out at the nine-month timepoint demonstrated a significant improvement in walk time compared to baseline in treated eyes compared to untreated eyes in the low and intermediate dose cohorts (n=6) [12].
Jul 20 · MeiraGTx and Janssen announce six-month data from the ongoing MGT009 clinical trial showing significant improvement in retinal sensitivity in the low (n=3) and intermediate (n=4) dose cohorts in the dose escalation phase of the trial [12].
Mar 20 · PI/II study (NCT04312672) expected to complete Jun 23 [9].
Mar 20 · Long-term follow-up PI/II study (NCT04312672; MGT010) is recruiting. The study started in Feb 19 and is recruiting 36 male patients receiving AAV2-RPGR in the MGT009 (NCT03252847) study. It will follow patients for up to 60 months [9].
Feb 20 · PI/II open label, multi-centre, dose ecalation trial (NCT03252847) of AAV2-RPGR in 46 adults and children with XLRP ongoing. The study is expected to complete in Nov 2020. (5,7)