laruparetigene zovaparvovec (AGTC-501) / AGTC - LARVOL DELTA

Beacon Therapeutics Announces Positive Phase 2 Interim 6-Month Data from DAWN Trial of Laru-zova in Patients with X-linked Retinitis Pigmentosa (XLRP) at ARVO 2025 (GlobeNewswire) - P2 | N=24 | DAWN (NCT06275620) | Sponsor: Beacon Therapeutics | "Key data highlights include: Ocular treatment-emergent adverse events (TEAEs) were generally non-serious and mild or moderate in severity, with a majority related to surgical procedures and steroids required by the protocol that have since resolved. There were no suspected unexpected serious adverse reactions, retinal detachments or endophthalmitis reported; Data demonstrated early improvements in low luminance visual acuity (LLVA), an important measure of visual function, with a greater number of two and three line improvements in the study eyes compared to previously treated fellow eyes in participants evaluated at month 6 or beyond....The Company continues to enroll patients for its pivotal Phase 2/3 VISTA trial of laru-zova for patients with XLRP."

P2 data • Trial status • Retinitis Pigmentosa

Beacon Therapeutics Announces ARVO 2025 Presentation on Preliminary 6-Month Data from its Phase 2 DAWN Trial of laru-zova in Patients with X-linked Retinitis Pigmentosa (XLRP) (PRNewswire) - "Beacon Therapeutics Holdings Limited...today announces an upcoming presentation on 6-month interim safety and efficacy results from the Phase 2 DAWN trial of the Company's lead program, laru-zova (laruparetigene zovaparvovec), in patients with X-linked retinitis pigmentosa (XLRP) at the Association for Research in Vision and Ophthalmology (ARVO) 2025 Annual Meeting being held May 4-8, 2025 in Salt Lake City."

P2 data • Retinitis Pigmentosa

Addressing Multiplicity in Retinal Sensitivity Analysis: An Alternative Approach to Assessing Gene Therapy Efficacy in Inherited Retinal Diseases. (PubMed, Transl Vis Sci Technol) - "We analyzed microperimetry data from a phase II trial of AGTC-501 in patients with X-linked retinitis pigmentosa (XLRP)...Using ≥7 unspecified loci as the criterion for assessing sensitivity changes, offers a comprehensive assessment that can detect genuine treatment effects without being overly conservative. This alternative statistical method has the potential to improve the evaluation of retinal sensitivity changes in gene therapy trials for IRDs, providing a more accurate measure of therapeutic efficacy and enhancing clinical decision making."

Clinical • Journal • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Subretinal gene therapy laru-zova (AGTC-501) for X-linked retinitis pigmentosa (XLRP): Phase 2 DAWN preliminary month 6 results (ARVO 2025) - "One eye had a serious side effect of glaucoma linked to corticosteroids used with treatment. This study is ongoing."

Gene therapy • P2 data • Glaucoma • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Pre-Clinical and Clinical Advances in Gene Therapy of X-Linked Retinitis Pigmentosa: Hope on the Horizon. (PubMed, J Clin Med) - "Recent clinical trials using AAV vectors, such as AAV5-RPGR and AGTC-501, have demonstrated encouraging results, including improvements in retinal sensitivity and visual function. While early successes like LUXTURNA have set the precedent for gene therapy in retinal diseases, adapting these strategies to XLRP presents unique challenges due to the complexity of RPGR mutations and the need for efficient photoreceptor targeting...Despite setbacks in some studies, ongoing research and clinical trials continue to refine these therapies, offering hope for patients affected by XLRP. This review explores the etiology and pathophysiology of XLRP, evaluates current treatment challenges, highlights recent clinical advances in gene therapy, and discusses future perspectives for bringing these therapies into clinical practice."

Journal • Preclinical • Review • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Beacon Therapeutics Granted FDA Regenerative Medicine Advanced Therapy (RMAT) Designation for laru-zova (AGTC-501) (PRNewswire) - "Beacon Therapeutics...announced that the U.S. Food and Drug Administration (FDA) has granted Regenerative Medicine Advanced Therapy (RMAT) designation to laru-zova (laruparetigene zovaparvovec) for the treatment of X-linked retinitis pigmentosa (XLRP)....The FDA's RMAT designation for laru-zova recognizes preliminary clinical evidence from the Phase 2 DAWN and SKYLINE trials evaluating the efficacy, safety and tolerability of laru-zova in patients with XLRP caused by mutations in the RPGR gene."

FDA event • Retinitis Pigmentosa

Subretinal Gene Therapy Drug AGTC-501 for XLRP Phase 1/2 Multicenter Study (HORIZON): 24-Month Safety and Efficacy Results: Subretinal Gene Therapy AGTC-501 for XLRP Ph 1/2 24M Results. (PubMed, Am J Ophthalmol) - "Subretinal AGTC-501 was generally well-tolerated. Despite all participants experiencing at least one TEAE, most of these events were mild in nature, exhibited complete resolution, and were associated with the subretinal injection procedure itself rather than the study agent. The highest dose exhibited an unfavorable risk-benefit profile due to the development of RPE changes. Although this group had the highest improvement in retinal sensitivity, our team has decided not to continue this dose in future clinical trials. Preliminary efficacy was observed at the maximum tolerated dose. Further studies are warranted to assess long-term safety and efficacy of AGTC-501 for XLRP treatment."

Clinical • Gene therapy • Journal • P1/2 data • Cataract • Gene Therapies • Genetic Disorders • Glaucoma • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

AGTC-RPGR-001: A Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (DAWN) (clinicaltrials.gov) - P2 | N=24 | Enrolling by invitation | Sponsor: Beacon Therapeutics | N=18 ➔ 24 | Trial completion date: Aug 2029 ➔ Dec 2029 | Trial primary completion date: Jul 2025 ➔ Nov 2025

Enrollment change • Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Subretinal AGTC-501 Gene Therapy for XLRP: Twenty-Four-Month Interim Results of the Phase 2 SKYLINE Trial (AAO 2024) - "Conclusion These Month-24 data demonstrate that both doses of AGTC-501 were generally safe and well tolerated. The favorable safety results support continued development of AGTC-501."

Gene therapy • P2 data • Inherited Retinal Dystrophy • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Subretinal gene therapy AGTC-501 for X-linked retinitis pigmentosa in the Phase 1/2 Horizon study: Post-hoc analysis of microperimetry results in the high dose groups (ARVO 2024) - "A post-hoc analysis of data from patients in the highest dose groups in Horizon who would have been eligible for the Phase 2 Skyline study was undertaken. These patients demonstrated efficacy on microperimetry consistent with emerging data from Skyline and a favorable safety profile. Follow-up is ongoing through 5 years to assess long-term safety and durability of response."

Gene therapy • P1/2 data • Retrospective data • Inherited Retinal Dystrophy • Ocular Infections • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With XLRP (clinicaltrials.gov) - P2/3 | N=75 | Recruiting | Sponsor: Beacon Therapeutics | Not yet recruiting ➔ Recruiting | Trial completion date: Mar 2029 ➔ Oct 2029 | Trial primary completion date: Jan 2024 ➔ Aug 2025

Enrollment open • Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

A Study Comparing Two Doses of AGTC-501 in Male Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (SKYLINE) (clinicaltrials.gov) - P2 | N=14 | Active, not recruiting | Sponsor: Beacon Therapeutics

New P2 trial • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

DAWN: A Phase 2 Multi-center Study Comparing Two Doses of AGTC-501 in Male Participants With X-linked Retinitis Pigmentosa Who Have Been Previously Treated With an AAV Vector-based Gene Therapy Designed to Provide Full-length Functioning RPGR Protein (clinicaltrials.gov) - P2 | N=18 | Enrolling by invitation | Sponsor: Beacon Therapeutics

Gene therapy • New P2 trial • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (clinicaltrials.gov) - P1/2 | N=29 | Active, not recruiting | Sponsor: Beacon Therapeutics | Recruiting ➔ Active, not recruiting | N=42 ➔ 29 | Trial completion date: Aug 2026 ➔ Mar 2025 | Trial primary completion date: Aug 2022 ➔ Nov 2023

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Subretinal Gene Therapy Drug AGTC-501 for X-Linked Retinitis Pigmentosa (XLRP) Phase 1/2 Multicenter Study (Horizon): 24-Month Interim Results (Macula 2023) - "The favorable safety profile over 24 months and encouraging efficacy outcomes strongly support continued clinical development of AGTC-501 in patients with XLRP."

Clinical • Gene therapy • P1/2 data • Cataract • Gene Therapies • Genetic Disorders • Glaucoma • Immunology • Inflammation • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Subretinal Gene Therapy Drug AGTC-501 for X-Linked Retinitis Pigmentosa Phase 2 Randomized, Controlled, Masked Multi-center Clinical Trial (Skyline) Interim Efficacy Results (Macula 2022) - "Initial follow up in these patients shows that the procedure and drug are well tolerated. These interim data will further determine the safety and efficacy profile of AGTC-501 to potentially treat patients with XLRP."

Clinical • P2 data • Gene Therapies • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

18 Month Analysis of Macular Structure using Optical Coherence Tomography (OCT) from a Phase 1/2 Clinical Study of Subretinal Gene Therapy Drug AGTC-501 for X-Linked Retinitis Pigmentosa (ARVO 2022) - "Consistent safety and efficacy signals in the study eyes that underwent subretinal administration of AGTC-501 were observed up through month 18. Of the study eyes with visible EZ at baseline, most showed recovery of foveal EZ after macular injection, and nearly half had improved EZ appearance which correlated with improvement in macular sensitivity. Follow-up is ongoing through 5 years to assess long-term safety and durability of response."

Clinical • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Clinically Meaningful Visual Improvements Demonstrated 12 Months After AGTC-501 Gene Therapy for X-linked Retinitis Pigmentosa (AAO 2021) - "Conclusion AGTC-501 shows a favorable safety profile and efficacy signals through Month 12. Clinically meaningful improvement in macular sensitivity and statistically significant improvement in BCVA were seen for the study eyes compared to the fellow eyes."

Clinical • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] Six Month Findings from a Phase 1/2 Clinical Study of Subretinal Gene Therapy Drug AGTC-501 for X-Linked Retinitis Pigmentosa Show Clinically Meaningful Improvement in Macular Sensitivity (ARVO 2021) - "Robust safety and efficacy signals in the study eyes of participants who underwent subretinal administration of AGTC-501 were observed through month 6. There was clinically meaningful improvement in macular sensitivity and statistically significant improvement in BCVA for the study eyes vs. untreated fellow eyes."

Clinical • P1/2 data • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

A Clinical Trial Evaluating the Safety and Efficacy of a Single Subretinal Injection of AGTC-501 in Participants With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (clinicaltrials.gov) - P2/3; N=63; Not yet recruiting; Sponsor: Applied Genetic Technologies Corp

New P2/3 trial • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

[VIRTUAL] Initial Safety and Immunological Findings from a Phase 1/2 Open-Label, Non-randomized Study Evaluating AGTC-501 (rAAV2tYF-GRK1-RPGR) Viral Vector in X-linked Retinitis Pigmentosa Male Patients (Macula 2021) - No abstract available

Clinical • P1/2 data • Genetic Disorders • Immunology • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (clinicaltrials.gov) - P1/2; N=42; Recruiting; Sponsor: Applied Genetic Technologies Corp; N=30 ➔ 42; Trial completion date: Mar 2025 ➔ Aug 2026; Trial primary completion date: Mar 2023 ➔ Aug 2022

Clinical • Enrollment change • Trial completion date • Trial primary completion date • Genetic Disorders • Inherited Retinal Dystrophy • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Dose Range Finding Studies with Two RPGR Transgenes in a Canine Model of X-linked Retinitis Pigmentosa Treated with Subretinal Gene Therapy. (PubMed, Hum Gene Ther) - "Subretinal administration of rAAV2tYF-GRK1-hRPGRco and rAAV2tYF-GRK1-hRPGRstb both corrected rod and cone opsin mislocalization, two early markers of disease in the XLPRA2 canine model of RPGR-XLRP. These results support the selection and use of rAAV2tYF-GRK1-hRPGRco (AGTC-501) and guided the initial doses in clinical studies in patients with XLRP caused by RPGR mutations."

Journal • Gene Therapies • Genetic Disorders • Immunology • Ocular Inflammation • Ophthalmology • Retinal Disorders • Retinitis Pigmentosa

Toxicity and Efficacy Evaluation of an AAV Vector Expressing Codon-Optimized RPGR Delivered by Subretinal Injection in a Canine Model of X-linked Retinitis Pigmentosa. (PubMed, Hum Gene Ther) - "The high-dose group showed evidence of both photoreceptor rescue and posterior segment toxicity. These results support the use of AGTC-501 in clinical studies with patients affected with XLRP caused by RPGR mutations and define the no-observed-adverse-effect-level (NOAEL) at 6 x 1011 vg/mL)."

Clinical • Journal

Safety and Efficacy of rAAV2tYF-GRK1-RPGR in Subjects With X-linked Retinitis Pigmentosa Caused by RPGR Mutations (clinicaltrials.gov) - P1/2; N=30; Recruiting; Sponsor: Applied Genetic Technologies Corp; N=15 ➔ 30; Trial completion date: Jan 2024 ➔ Mar 2025; Trial primary completion date: Jan 2022 ➔ Mar 2023

Enrollment change • Trial completion date • Trial primary completion date