sepofarsen (QR-110) / ProQR - LARVOL DELTA

Efficacy, Safety, and Durability of Gene Therapy for Inherited Retinal Diseases in the Paediatric Population: A Scoping Review. (PubMed, Am J Ophthalmol) - "Paediatric benefit from IRD gene therapy depends on genotype, residual retinal structure, therapeutic platform, dose, surgical strategy, and outcome measure. The major evidence gaps are long-term paediatric durability and inconsistent age-stratified reporting. Future paediatric-inclusive trials should pre-specify subgroup analyses, embed prospective long-term follow-up, use developmentally appropriate endpoints, and report individual-level data sufficient to support paediatric inference."

Journal • Review • Cataract • Gene Therapies • Ophthalmology • Pediatrics • Retinal Disorders • CEP290 • GUCY2D • MERTK

Ora visual navigation course™ mobility test results in two individuals with CEP290 LCA after intravitreal injection of antisense oligonucleotide. (PubMed, Ophthalmic Genet) - "This study aimed to report the longitudinal Ora Visual Navigation Course (Ora VNC™) mobility test results in two individuals, with CEP290 LCA following intravitreal injections of an antisense oligonucleotide, sepofarsen...According to the technicians' report, both subjects demonstrated an increase in perceived obstacle recognition during iterations, which may reflect improvement of mobility-based visual function outcomes. The Ora VNC™ mobility test captured mobility-based visual function gains, including subtle spatial improvements, but may lack sensitivity in individuals with extremely low vision, potentially overlooking small but patient-relevant changes."

Journal • Inherited Retinal Dystrophy • CEP290

Post-hoc analysis emulating a paired-eye design of the ILLUMINATE trials suggests efficacy of sepofarsen in CEP290-associated Leber congenital amaurosis (LCA) 10. (ARVO 2026) - P2/3, P3 | "The paired-eye analysis demonstrates improvements in participants that were not previously shown due to the limitations of the clinical trial design. This shows the importance of new trial designs for rare diseases."

Clinical • Retrospective data • Diabetic Retinopathy • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

Multimodal clinical outcomes improve detection of treatment response in CEP290-associated Leber congenital amaurosis (LCA) 10 in a post-hoc analysis of the ILLUMINATE trial (ARVO 2026) - P2/3 | "About two-thirds or 67% of participants showed improvement in at least 1 of these areas in their treated eye, suggesting that sepofarsen can provide meaningful visual benefits for some people with LCA10. These findings show that combining multiple types of visual tests can give a clearer picture of how emerging treatments help people with rare inherited retinal disorders."

Clinical • Clinical data • Retrospective data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

Comparing the safety profile of sepofarsen, an investigational antisense oligonucleotide for CEP290-associated Leber congenital amaurosis (LCA) 10, in pediatric and adult populations (ARVO 2026) - P3 | "Overall, the safety profile of sepofarsen was similar across age groups, with manageable side effects that were related to the treated eye. Ongoing long-term monitoring and the new HYPERION Phase 3 trial will help confirm these findings and support the continued development of potential treatments for IRDs."

Clinical • Cataract • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

An Atlas of Human Pathogenic Variants for Splice-Switching Oligonucleotide Therapy (ACMG 2026) - "CEP290 c.2991+1655A>G (10.8/year), targeted by sepofarsen in ongoing Phase 3 trials for Leber congenital amaurosis, ranked sixth, validating the potential for independent clinical trials targeting highly prevalent variants... This study provides a comprehensive atlas of recurrent ASO-amenable variants, establishing a scalable framework for prioritizing ASO development. The data strongly support pre-emptive "drug warehousing," particularly for ocular disorders that dominate highly prevalent targets. Prioritizing genes with multiple amenable variants enables repurposing of preclinical models, functional assays, and clinical protocols, significantly improving cost-efficiency."

Ataxia • Genetic Disorders • Immunology • Inherited Retinal Dystrophy • Movement Disorders • Ocular Inflammation • Ophthalmology • Primary Immunodeficiency • Retinal Disorders • Retinitis Pigmentosa • CDH1 • CEP290 • USH2A

Clinical Research for Inherited Retinal Disease Related Pediatric Blindness: A Preliminary Descriptive Analysis Based on ClinicalTrials.gov. (PubMed, J Multidiscip Healthc) - "On interventions, the most commonly used approaches for handling childhood blindness include gene therapy vectors like AAV RPE65, antisense oligonucleotides like QR-110, and repurposed pharmacological agents such as lithium and dantrolene sodium. The dominance of early-phase studies highlights the need for expanded, multicenter, and later-phase trials. Future research should aim to improve trial accessibility, standardize outcome measures, and ensure ethical conduct in pediatric populations."

Journal • Achromatopsia • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Leber Hereditary Optic Neuropathy • Metabolic Disorders • Nephrology • Ocular Inflammation • Ophthalmology • Optic Neuritis • Osteoporosis • Pediatrics • Retinal Disorders • Retinitis Pigmentosa • Rheumatology • Solid Tumor

Study to Evaluate Sepofarsen in Subjects With Leber Congenital Amaurosis (LCA) Type 10 (HYPERION) (clinicaltrials.gov) - P3 | N=32 | Recruiting | Sponsor: Laboratoires Thea | Not yet recruiting ➔ Recruiting | Initiation date: Mar 2025 ➔ Aug 2025

Enrollment open • Trial initiation date • CNS Disorders • Conjunctivitis • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

RNA-based therapy in Leber congenital amaurosis type 10 (LCA10): key lessons learned from the randomized double-masked, sham-controlled Phase 3 study of sepofarsen (ARVO 2025) - "The study aimed at understanding the inconsistencies observed in the results from a previously conducted clinical study and whether a change of study design to a paired-eye paradigm (i.e., comparing eyes with and without treatment within the same patient) in a clinical study would be better.Visual acuity, or eye chart improvements of approximately 8 letters gain on a standard eye chart were seen after 12 months of treatment when the two eyes were compared to each other in 15 individuals included in the analysis. In general, reduced variability (less noise in measurement) was observed across the two eyes in visual function assessments.These results showed that comparing eyes of a clinical trial participant in a study in this rare disease is a better way of identifying treatment response of sepofarsen in LCA10 patients."

Clinical • P3 data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

Freiburg Vision Test (FrACT) for assessing visual acuity in Leber congenital amaurosis type 10 (LCA10) patients (ARVO 2025) - "In this study we compared BCVA assessments with FrACT to those with ETDRS extended with BRVT using data from a phase 3 trial (ILLUMINATE) evaluating the efficacy of RNA-therapy sepofarsen in LCA10...Repeatability is important in clinical test analysis. Therefore, the FrACT test appears to be a good clinical test to assess vision in individuals and future clinical trial participants with ultra-low vision."

Clinical • Inherited Retinal Dystrophy • Ophthalmology • CEP290

Study to Evaluate Sepofarsen in Subjects with Leber Congenital Amaurosis (LCA) Type 10 (HYPERION) (clinicaltrials.gov) - P3 | N=32 | Not yet recruiting | Sponsor: Laboratoires Thea

New P3 trial • CNS Disorders • Conjunctivitis • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

Long durability of foveal cone vision improvement after single injections of sepofarsen confirmed in a second CEP290-LCA eye (ARVO 2023) - "Layman Abstract (optional): Provide a 50-200 word description of your work that non-scientists can understand. Describe the big picture and the implications of your findings, not the study itself and the associated details."

Ophthalmology • CEP290

INSIGHT: Extension Study to Study PQ-110-001 (NCT03140969) (clinicaltrials.gov) - P1/2 | N=9 | Terminated | Sponsor: ProQR Therapeutics | Trial completion date: May 2023 ➔ Oct 2022 | Active, not recruiting ➔ Terminated | Trial primary completion date: May 2023 ➔ Oct 2022; Terminated [Study prematurely terminated due to sponsor decision for reasons unrelated to safety]

Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

RNA-based therapies in inherited retinal diseases. (PubMed, Ther Adv Ophthalmol) - "These RNA-based therapies bring several key advantages in the setting of IRDs, and the potential to bring meaningful vision benefit to individuals living with inherited blinding disorders. This review will examine the increasing breadth and relevance of RNA-based therapies in clinical medicine, explore the key features that make AONs suitable for treating genetic eye diseases, and provide an overview of the three-leading investigational AONs in clinical trials."

Journal • Review • Ophthalmology • Rare Diseases • Retinal Disorders

Restoration of Cone Sensitivity to Individuals with Congenital Photoreceptor Blindness within the Phase 1/2 Sepofarsen Trial. (PubMed, Ophthalmol Sci) - "However, translation of increased light sensitivity to improved spatial vision may occur preferentially in those with a history of visual experience during early neurodevelopment. Interventions for congenital lack of spatial vision in CEP290-associated Leber congenital amaurosis may lead to better results if performed before visual cortex maturity."

Journal • P1/2 data • Inherited Retinal Dystrophy • Ophthalmology • CEP290

Efficacy and safety of sepofarsen, an intravitreal RNA antisense oligonucleotide, for the treatment of CEP290-associated Leber congenital amaurosis (LCA10): a randomized, double-masked, sham-controlled, Phase 3 study (ILLUMINATE) (ARVO 2022) - P2/3 | "Sepofarsen, an innovative RNA antisense oligonucleotide, is the most advanced program in development for the treatment of LCA10. Learning from recruitment suggested the commonality of the c.2991+1655A>G variant in LCA10. Updated results will be included as available."

Clinical • P3 data • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

Long-term safety and efficacy of sepofarsen in a Ph1b/2 INSIGHT extension trial in CEP290-associated Leber congenital amaurosis (LCA10) (ARVO 2022) - P1/2, P2/3 | "The longer-term sepofarsen safety profile is consistent with that observed in the Ph1b/2. Meaningful BCVA and FST improvements observed in the Ph1b/2 continued up to 46 months. The responses in the SE were similar to the responses seen in the FE in both visual acuity and retinal sensitivity improvements."

Clinical • P1/2 data • Cataract • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

Intravitreal antisense oligonucleotide sepofarsen in Leber congenital amaurosis type 10: a phase 1b/2 trial. (PubMed, Nat Med) - P1/2 | "Statistically significant improvements in visual acuity and retinal sensitivity were reported (post hoc analysis). The manageable safety profile and improvements reported in this trial support the continuation of sepofarsen development."

Journal • P1/2 data • Cataract • Inherited Retinal Dystrophy • Ophthalmology • Pediatrics • Retinal Disorders • CEP290

A Study to Evaluate Efficacy, Safety, Tolerability and Exposure After a Repeat-dose of Sepofarsen (QR-110) in LCA10 (ILLUMINATE) (clinicaltrials.gov) - P2/3 | N=36 | Active, not recruiting | Sponsor: ProQR Therapeutics | Trial completion date: Dec 2021 ➔ Mar 2023

Trial completion date • CNS Disorders • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

INSIGHT: Extension Study to Study PQ-110-001 (NCT03140969) (clinicaltrials.gov) - P1/2 | N=11 | Active, not recruiting | Sponsor: ProQR Therapeutics | Trial completion date: May 2022 ➔ May 2023 | Trial primary completion date: May 2022 ➔ May 2023

Trial completion date • Trial primary completion date • CNS Disorders • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders

[VIRTUAL] A Different Type of Genetic Therapy: Correcting A Defective Gene Using Antisense Oligonucleotide Treatment in CEP290 p.Cys998X LCA (AAPOS 2021) - "Eleven subjects were enrolled. Reported cases of cataracts, mild cystoid macular edema, and retinal thinning were 3, 0, and 0, respectively, in the 160µg/80µg group; 5, 2, and 2 in the 320µg/160µg group. No other safety concerns were identified."

Cataract • Gene Therapies • Macular Edema • Ophthalmology • Retinal Disorders • CEP290

[VIRTUAL] Safety and efficacy of sepofarsen in the second treated eye in a Ph1b/2 extension trial in Leber Congenital Amaurosis type 10 (LCA10) (ARVO 2021) - P1/2, P2/3 | "This data analysis strongly corroborates the clinically meaningful vision improvements and safety profile observed in the Ph1b/2 trial. Second eye responses to sepofarsen parallel the first eye treated responses both in visual acuity and retinal sensitivity (FST) improvements. Sepofarsen safety profile for the 160/80µg dose group in this extension trial is consistent with that observed in the Ph1b/2 trial."

Clinical • P1/2 data • Cataract • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders • CEP290

"$PRQR ProQR Announces Publication in Nature Medicine for Sepofarsen in Leber Congenital Amaurosis 10 https://t.co/dF1nHySz9H" (,@stock_titan)

Inherited Retinal Dystrophy

BRIGHTEN: An Open-label, Dose Escalation and Double-masked, Randomized, Controlled Trial Evaluating Safety and Tolerability of Sepofarsen in Children (<8 Years of Age) With LCA10 Caused by Mutations in the CEP290 Gene. (clinicaltrials.gov) - P2/3; N=15; Recruiting; Sponsor: ProQR Therapeutics

New P2/3 trial • CNS Disorders • Inherited Retinal Dystrophy • Ophthalmology • Pediatrics • Retinal Disorders • CEP290

INSIGHT: Extension Study to Study PQ-110-001 (NCT03140969) (clinicaltrials.gov) - P1/2; N=11; Active, not recruiting; Sponsor: ProQR Therapeutics; Trial completion date: Mar 2021 ➔ May 2022; Trial primary completion date: Mar 2021 ➔ May 2022

Clinical • Trial completion date • Trial primary completion date • CNS Disorders • Inherited Retinal Dystrophy • Ophthalmology • Retinal Disorders