Janssen’s Gene Therapies Show Promise in Retinitis Pigmentosa, Geographic Atrophy


Both botaretigene sparoparvovec and JNJ-81201887 were well-tolerated in treated patients, according to data from the 2022 AAO meeting.

Janssen’s gene therapies botaretigene sparoparvovec and JNJ-81201887 (JNJ-1887) have shown safety and promising signs of efficacy in treating inherited retinal disease X-linked retinitis pigmentosa (XLRP) associated with the retinitis pigmentosa GTPase regulator (RPGR) gene (NCT03252847) and geographic atrophy (GA) in dry age-related macular degeneration (AMD; NCT03144999), respectively.1,2

These data were presented at the American Academy of Ophthalmology (AAO) annual meeting taking place September 30 – October 1 in Chicago, Illinois. Michel Michaelides, MD, FRCOphth, professor, University College London Institute of Ophthalmology and Moorfields Eye Hospital, London, presented the data on botaretigene sparoparvovec while Michael Nathan Cohen, MD, retina service, Wills Eye Hospital, Thomas Jefferson University, presented data on JNJ-1887.

"Individuals living with XLRP often begin to experience symptoms in childhood, and as retinal degeneration progresses toward blindness, they can start to feel a sense of hopelessness as there are no treatments to turn to," Michaelides, who is lead investigator on the study, said in a statement."These results from the MGT009 study are promising, as they represent the potential for botaretigene sparoparvovec to preserve vision and ultimately restore hope for these patients."

Subretinal delivery of botaretigene sparoparvovec in 1 eye is being investigated in collaboration with MeiraGTx in the phase 1/2 MGT009 study. It is designed to deliver functional copies of the RPGR gene to preserve and potentially restore vision due to the loss of retinal cells. The study primarily evaluated safety and secondary endpoints evaluated retinal sensitivity, visual function and functional vision. The study comprised 3 parts: dose-escalation, pediatric dose-confirmation and an expansion phase. The first phase investigated 2x1011 vg/mL, 4x1011 vg/mL, and 8x1011 vg/mL doses. The expansion phase randomized 42 adult male patients to treatment with 1 of 2 low or intermediate doses or an untreated concurrent control arm with deferred treatment (randomized to receive the low or intermediate doses at 6 months). The 3 patients in the pediatric cohort were treated with the intermediate dose.

READ MORE: Wet AMD Gene Therapy Reduces Anti-VEGF Treatment Burden

Investigators found that retinal sensitivity, visual function and functional vision improved or sustained function with a significant difference compared to the randomized untreated control arm 6 months after treatment. Mean retinal sensitivity was found to improve in treated eyes compared to untreated eyes in the concurrent control arm, as measured by static perimetry in the central 10-degree area of the retina (1.96 decibel [dB; 95% CI, 0.59-3.34]; and in a further sensitivity analysis 2.42 dB [95% CI, 0.91-3.93]). Improvements were also observed in walk time of a visual mobility maze between treated and untreated eyes at week 26 (full analysis nominal P-value <.05 at lux 1 and lux 16; in a further sensitivity analysis, nominal P-value <.01 at lux 1, lux 4 and lux 16). The sensitivity analysis applied the Phase 3 LUMEOS study (NCT04671433) eligibility criteria to support the endpoints selected in the MGT009 study.

Botaretigene sparoparvovec has had a consistent, manageable safety profile across studies. There were no dose-limiting toxicities (DLTs) and most adverse events (AEs) were transient, related to surgical delivery, and resolved without intervention. The study had 3 serious AEs: retinal detachment, panuveitis and increased ocular pressure.

"Without an approved treatment option available, people with XLRP are faced with the inevitable fate of going blind in the prime of life," James List, MD, PhD, global therapeutic area head, cardiovascular, metabolism, retina & pulmonary hypertension, Janssen, added to the statement.3 "We're in a race to save sight for these patients and are encouraged by the strength of the data that we've shared so far. We look forward to advancing the clinical development of botaretigene sparoparvovec as part of our mission to preserve and potentially restore vision for these patients."

A single intravitreal injection of JNJ-1887 was well-tolerated in 17 patients enrolled in Janssen’s other phase 1 study presented.2 Low, intermediate and high doses of the therapy, without steroid prophylaxis, were all well-tolerated with acceptable safety over the 2-year follow-up period. There were no DLTs or treatment-related serious AEs. Exploratory efficacy measures, including evaluation of GA lesion growth rates, continuously declined over 6-month increments up to 24 months in the high-dose cohort.

“We’re pleased to report the first results of JNJ1887 in patients with GA, which was found to be safe and tolerable in all dose cohorts evaluated up to the extended 24-month follow up. The inflammation profile was manageable even without steroid prophylaxis.Welook forward to a forthcoming phase 2 trial using JNJ1887 as a treatment in patients with GA,” Cohen said during his presentation.2

1. Michaelides M. Ph1/2 AAV5-RPGR (botaretigenesparoparvovec) gene therapy trial in RPGR-associated X-linked retinitis pigmentosa (XLRP). Presented at: 2022 AAO Annual Meeting. Section X: Late Breaking Developments, Part 2. 
2.Cohen MN. Phase 1 study of JNJ-81201887 gene therapy in geographic atrophy (GA) due to age-related macular degeneration (AMD). Presented at: 2022 AAO Annual Meeting. Section X: Late Breaking Developments, Part 2.
3. Janssen announces late-breaking data from two gene therapy programs at the American Academy of Ophthalmology 2022 Annual Meeting. News release. Janssen. October 1, 2022. https://www.prnewswire.com/news-releases/janssen-announces-late-breaking-data-from-two-gene-therapy-programs-at-the-american-academy-of-ophthalmology-2022-annual-meeting-301638346.html
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