Treatment with botaretigene sparoparvovec was found to have an acceptable safety profile, and efficacy assessments in this proof-of-concept study demonstrated encouraging improvements in retinal sensitivity, visual function and functional vision.1 These findings and additional updates, including data from a Phase 1 trial of investigational gene therapy JNJ-81201887 (JNJ-1887) for patients with geographic atrophy (GA), a late-stage and severe form of age-related macular degeneration (AMD), were presented in late-breaking oral presentations today at the Retina Subspecialty Day program of the
XLRP is a rare condition estimated to impact one in 40,000 people globally.2,3 People with XLRP have progressive vision loss, starting in childhood with night blindness.4 Over time, they lose their peripheral vision leading to legal blindness by middle age.4 Botaretigene sparoparvovec is being investigated in collaboration with
'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,' said
The primary endpoint of the MGT009 study (NCT03252847) was safety, with secondary endpoints measuring changes in assessments of three domains of vision-retinal sensitivity, visual function and functional vision-at specified time points post-treatment.1 In the study's dose escalation and expansion phases, significant sustained or increased functional improvement in each visual domain was observed in participants treated with botaretigene sparoparvovec compared to the randomized untreated control arm of the study at six months post-treatment.1
Analyses of the pooled low and intermediate dose cohorts demonstrated improvement in retinal sensitivity in the treated eyes compared to untreated eyes in the randomized concurrent control arm as measured by both full-field static perimetry and microperimetry.1 An improvement in mean retinal sensitivity as measured by static perimetry in the central 10-degree area of the retina was observed at six months in the treated eyes compared to untreated eyes in the randomized concurrent 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
As part of the study, patients performed a functional vision assessment using a visual mobility maze to assess their ability to navigate through simulated real-life obstacles across a broad range of controlled light. At week 26, improvement in walk time was observed between the treated eyes in the low and intermediate dose cohorts and the untreated eyes in the randomized concurrent control arm at low illumination levels (full analysis nominal p-value < 0.05 at lux 1 and lux 16; in the sensitivity analysis when applying the Phase 3 criteria 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.1 Botaretigene sparoparvovec demonstrated an adverse event (AE) profile that was anticipated and manageable.1 Most AEs were related to the surgical delivery procedure, were transient and resolved without intervention.1 There were no dose-limiting events.1 A total of three serious adverse events (SAEs) were observed in the overall Phase 1/2 MGT009 clinical study; two SAEs, which were previously reported, were observed in the dose-escalation phase of the study (n=10; one retinal detachment and one panuveitis in the low dose cohort), and a single additional SAE of increased intraocular pressure was observed in the dose escalation phase and resolved with treatment.1
'Without an approved treatment option available, people with XLRP are faced with the inevitable fate of going blind in the prime of life,' said
Further sensitivity analysis was conducted on study participants by applying the Phase 3 LUMEOS (NCT04671433) study eligibility criteria that corroborated the endpoints selected for the Phase 3 study.1 Currently, the LUMEOS study of botaretigene sparoparvovec for the treatment of patients with XLRP with disease-causing variants in the RPGR gene is actively dosing patients.
Phase 1 Data Evaluating JNJ-1887 in Geographic Atrophy
Janssen also presented late-breaking data from a Phase 1, open-label, multicenter, dose-escalation, safety and tolerability study (NCT03144999) of a 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 impact on GA patients' health-related quality of life, including their ability to read, drive and perform other day-to-day activities.5 In this study, patients (n=17) were sequentially enrolled at a low, intermediate and high dose without steroid prophylaxis, and all three doses of JNJ-1887 met the primary endpoint of safety over the two-year follow-up period.6 In addition, the supportive efficacy measures, including evaluation of GA lesion growth rates, showed a continual decline in lesion growth over six-month increments.6 These results are the first shared from the Company's common eye disease portfolio and indicate further evaluation of this investigational gene therapy is warranted.6
About the Phase 1/2 MGT009 Trial and Botaretigene Sparoparvovec
The Phase 1/2 MGT009 trial (NCT03252847) was an open-label, multicenter dose escalation study that enrolled patients aged five years and older with X-linked retinitis pigmentosa (XLRP) caused by disease causing variants in the retinitis pigmentosa GTPase regulator (RPGR) gene at multiple sites in
The clinical study was composed of three parts: dose-escalation, pediatric dose-confirmation and an expansion phase. In the dose escalation phase, adult patients were treated at three escalating doses of botaretigene sparoparvovec; a low (2x1011 vg/mL), an intermediate (4x1011 vg/mL), and a high (8x1011 vg/mL) dose. In the expansion phase, 42 adult male patients were randomized to either immediate treatment with one of two low or intermediate doses or an untreated concurrent control arm with deferred treatment. At six months, the untreated control arm was randomized to receive either the low or intermediate treatment doses. Botaretigene sparoparvovec was administered through subretinal delivery in only one eye. The adult patients received treatment at three doses. The pediatric cohort (n=3) was only treated with an intermediate dose of botaretigene sparoparvovec.
Botaretigene sparoparvovec has been granted Fast Track and Orphan Drug designations by the
About the Janssen and MeiraGTx Strategic Collaboration
In
About the Phase 1 JNJ-1887 Trial and JNJ-1887
JNJ-81201887 (JNJ-1887), formerly 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 was evaluated in a Phase 1 clinical trial (NCT03144999), an open-label, single-center dose escalation study to determine the safety of JNJ-1887 in adults 50 or older with advanced dry AMD with GA. The patients were treated at three escalating doses of JNJ-1887 without steroid prophylaxis through a single intravitreal injection in one eye.
This Phase 1 study met its primary endpoint of safety in all doses of JNJ-1887 (n=17), with supportive efficacy measures including evaluation of GA lesion growth rates, which showed a continual decline in lesion growth over six-month increments.
JNJ-1887 has been granted Fast Track designation by the
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Cautions Concerning Forward-Looking Statements
This press release contains 'forward-looking statements' as defined in the Private Securities Litigation Reform Act of 1995 regarding botaretigene sparoparvovec and JNJ-81201887. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of
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