Janssen announces the latest data from two gene therapy programs

Janssen Pharmaceutical Companies of Johnson & Johnson announces preliminary results from a Phase 1/2 study evaluating investigative gene therapy botaretigene sparoparvovec (formerly AAV-RPGR) in patients with hereditary retinitis pigmentosa (XLRP)-associated retinitis. pigmentary; The retinitis pigmentosa regulator gene GTPase (RPGR).

The announcement was made Friday during late oral presentations on Retina Subspecialty Day at the American Academy of Ophthalmology 2022 Annual Meeting at McCormick Place in Chicago.

According to the company, treatment with sparoparvove botaretigene was found to have an acceptable safety profile, and efficacy evaluations in this proof-of-concept study showed encouraging improvements in retinal sensitivity, visual function and functional vision.1

Jansen noted in a press release that these findings and additional updates, including data from the JNJ-81201887 phase 1 trial of investigative gene therapy (JNJ-1887) for patients with geographic atrophy (GA), a late-stage and severe form of macular degeneration Age-related (AMD).

XLRP is a rare condition estimated to affect 1 in 40,000 people globally.2,3 People with XLRP have progressive vision loss, beginning in childhood with night blindness.4 Over time, they lose their peripheral vision resulting in legal blindness by middle age.4 Botaretigene sparoparvovec is being investigated in collaboration with MeiraGTx Holdings plc to treat patients with XLRP caused by pathogenic variants in the eye-specific form of the RPGR (RPGR (ORF15) gene).

The company also noted that through one-time administration, sparoparvove botaretigene was designed to deliver functional copies of the RPGR gene to counteract retinal cell loss with the goal of preserving and restoring vision in those living with XLRP. Currently, there are no approved treatments for XLRP.4

“Individuals living with XLRP often begin to experience symptoms in childhood, and as retinal degeneration progresses toward blindness, they can begin to feel hopeless that there are no treatments to turn to,” said Michael Michaelides, MD, MBBS, MBBS. MD (Res), FRCOphth, FACS, Consultant Ophthalmologist, Moorfields Eye Hospital, Professor of Ophthalmology, University College London and Principal Investigator. vision and ultimately restoring hope to these patients.”

Furthermore, the company noted that the primary endpoint of the MGT009 study (NCT03252847) was safety, with secondary endpoints measuring changes in assessments of three fields of vision—retinal sensitivity, visual function, and functional vision—at specific time points after treatment.1 In the dose escalation and expansion phases of the study, significant, sustained or increased functional improvement in each visual field was observed in participants treated with botaretigene sparoparvovec compared to the study’s untreated randomized control arm at six months after treatment.1

According to Janssen, analyzes of the combined low and medium dose groups showed an improvement in retinal sensitivity in the treated eye compared to untreated eyes in the synchronously randomized control arm as measured by both fixed full-field perimetry and micrometry. Sensitivity measured by constant peripheral measurement in the central area of ​​the retina of 10 degrees at six months was observed in the treated eye compared to untreated eyes in the randomized synchronous control arm. [in the full analysis of pooled low and intermediate doses across adults: 1.96 decibel (dB); (±95% CI: 0.59, 3.34); and in the sensitivity analysis when applying the Phase 3 criteria: 2.42 (0.91, 3.93)].1

The company also noted that as part of the study, patients had a functional vision assessment using a visual motion maze To assess their ability to navigate realistic, simulated obstacles across a wide range of controlled light. At week 26, improvement in walking time between treated eyes in the low and medium dose groups and untreated eyes was observed in the synchronous, randomized control arm at low light levels (nominal p-value for the full analysis <0.05 at lux 1 and lux 16; in sensitivity analysis when criteria were applied Phase 3, nominal p-value < 0.01 at lux 1, lux 4 and lux 16).1

The safety profile of botaretigene sparoparvovec observed in MGT009 was consistent with previous reports. Botaretigene sparoparvovec showed a predictable and controllable adverse event (AE) profile.1 Most AEs were related to the surgical delivery procedure, were transient and resolved without intervention.1 There were no dose-setting events.1 A total of three serious adverse events (SAEs) were observed in the comprehensive Phase 1/2 MGT009 clinical study; Two SAEs, previously reported, were observed in the dose-escalation phase of the study (n = 10; one retinal detachment and one panniculitis in the low-dose group), and one additional SAE of increased intraocular pressure was observed in the dose-escalation phase and resolved with treatment.1

James List, MD, chair of the Global Therapeutic Area, Cardiovascular, Metabolic, Retinal and Lung Hypertension, Janssen Research & Development, LLC. “We are in a race to save sight for these patients and are encouraged by the strength of the data we have shared so far. We look forward to advancing the clinical development of sparoparvovec butaretigin as part of our mission to preserve vision recovery for these patients.”

Further sensitivity analysis was performed on the study participants by applying the Phase 3 LUMEOS (NCT04671433) Examine the eligibility criteria that supported the endpoints selected for the Phase 3 study.1 Currently, the LUMEOS study of sparoparvovec butyrate for the treatment of patients with XLRP with pathogenic variants in the RPGR gene is to administer effective doses to patients.

Phase I evaluation of JNJ-1887 data in geographic atrophy
Janssen also presented recent data from a Phase 1, open-label, multicenter, dose escalation, safety and tolerability study (NCT03144999A single intravitreal injection of JNJ-1887 in patients with advanced non-exudative (dry) age-related macular degeneration (AMD) with GA. GA is an irreversible condition that affects more than five million individuals worldwide.5 It has a devastating effect on the quality of life related to the health of GA patients, including their ability to read, drive, and perform other daily activities.5 In this study, patients (n = 17) were enrolled sequentially on low, medium, and high dose without steroid prophylaxis, and all three doses of JNJ-1887 achieved the primary safety endpoint during the 2-year follow-up period. In addition, supportive efficacy measures, including assessment of GA lesion growth rates, demonstrated a sustained reduction in lesion growth over a period of six months. Gene therapy is justified.6

Around Phase 1/2 MGT009 Experimental and Botaretigene Sparoparvovec
Phase Trial 1/2 MGT009 (NCT03252847) is an open, multicenter dose-escalation study involving patients aged five years and older with X-linked retinitis pigmentosa (XLRP) caused by disease-causing variants in the retinitis pigmentosa regulator (RPGR) gene at multiple sites in the United States and the United Kingdom. United. The primary end point was safety and tolerability; Secondary endpoints assessed retinal sensitivity, visual function, and functional vision.

The clinical study consists of three parts: dose escalation, pediatric dose confirmation, and expansion phase. In the dose escalation phase, adult patients were treated with three escalating doses of butaretigin-sparoparathyroid; Low dose (2×1011 vg/mL), intermediate (4×1011 vg/mL), and high dose (8×1011 vg/mL). In the expansion phase, 42 adult patients were randomized to either immediate treatment with one of two low or intermediate doses or an untreated simultaneous control arm with deferred treatment. At six months, the untreated control arm was randomly selected to receive the low or medium treatment doses. Botaretigene sparoparvovec was administered by subretinal delivery in only one eye. Adult patients received treatment with three doses. The pediatric group (n = 3) was treated only with an intermediate dose of sparoparvovic butaretin.

Botaretigene sparoparvovec has been granted Fast Track and Orphan Drug designations by the US Food and Drug Administration (FDA), PRIority medicines (PRIME), Advanced Therapeutic Medicinal Products (ATMP) and orphan designations by the European Medicines Agency (EMA).

about Janssen and MeiraGTx strategic cooperation
In January 2019, Janssen Research and Development, LLC . entered Global cooperation and licensing agreement With MeiraGTx Holdings plc, a clinical stage gene therapy company, to develop, manufacture and market a portfolio of clinical stage inherited retinal diseases. Botaretigene sparoparvovec is being developed as part of a cooperation and licensing 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 vector design, optimization and fabrication.

About the JNJ-1887 and JNJ-1887 Phase I Trial
JNJ-81201887 (JNJ-1887), previously referred to as AAVCAGsCD59, is an investigational gene therapy for the treatment of people with geographic atrophy (GA) secondary to dry age-related macular degeneration (AMD). JNJ-1887 is designed to increase the expression of a soluble form of CD59 (sCD59) intended to protect retinal cells to slow and prevent disease progression. JNJ-1887 has been evaluated in a phase I clinical trial (NCT03144999), a single-center, open-label dose escalation study to determine the safety of JNJ-1887 in adults 50 years of age or older with advanced dry AMD with GA. Patients were treated with three escalating doses of JNJ-1887 without steroid prophylaxis through a single intravitreal injection into one eye.

This phase I study achieved the primary safety endpoint in all doses of JNJ-1887 (n=17), with supportive efficacy measures including assessment of GA lesion growth rates, which showed a sustained reduction in lesion growth over six months.

JNJ-1887 has been granted Fast Track designation by the FDA and Advanced Therapy Medicinal Product (ATMP) by the European Medicines Agency (EMA).


1 Michaelides, M et al. Ph1/2 AAV5-RPGR (Botaretigene Sparoparvovec) gene therapy trial in RPGR-associated retinitis pigmentosa (XLRP). Abstract #30071754. Presented at the 2022 American Academy of Ophthalmology Annual Meeting.
22 Boughman JA, Conneally PM, Nance WE. Population genetic studies of retinitis pigmentosa. I’m J Hum Genet. 1980; 32 (2): 223-235.
3 Fishman GA. Retinitis pigmentosa. genetic percentages. eyes arc. 1978; 96 (5): 822-826. doi: 10.1001/archopht.1978.03910050428005.
4 Wang D.Y., Chan WM, Tam Po, et al. Gene mutations in retinitis pigmentosa and their clinical implications. Clean Chem Acta. 2005; 351 (1-2): 5-16.
5 Cohen, MN et al. Phase 1 study JNJ-81201887 gene therapy in geographic degeneration (GA) due to age-related macular degeneration (AMD). Abstract #30071749. Presented at the 2022 American Academy of Ophthalmology Annual Meeting.
6 Singh RP, Patel SS, Neilsen JS, et al. Patient, caregivers, and ophthalmologists have reported the burden of geographic atrophy secondary to age-related macular degeneration. Am J Ophthalmic Clinic Trials. 2019; 2 (1): 1-6.

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