6-Month summary of gene therapy advances in ocular diseases

Rare retinal diseases initially were the primary targets of gene therapy, but that is no longer the case. The focus has expanded beyond those to also include more common, chronic diseases such as diabetic macular edema (DME) and wet age-related macular degeneration (AMD). During the first half of 2026, that trend was evident. Here are some of the key advances in the gene therapy arena seen over the previous 6 months.

Wet AMD. While anti-vascular endothelial growth factor (VEGF) drugs currently are the mainstay of treatment that has facilitated extended dosing regimens and lower treatment burdens, gene therapy for wet AMD is moving in the same direction to achieve treatment durability. The following are some of the highlights.

4D-150, an investigational gene therapy for wet AMD, administered as one in-office ocular injection, uses an engineered virus to deliver genes that cause the eye's own cells to continuously produce proteins that block multiple VEGFs.¹

4D Molecular Therapeutics completed enrollment in the 4FRONT-1 and 4FRONT-2 phase 3 clinical programs of 4D-150 on February 9 and June 29, respectively. The respective phase 3 results are expected in early 2027 and second quarter 2027.² The program aims to provide multiyear sustained delivery of anti-VEGF biologics after one intravitreal injection.³

Geographic atrophy. Ocugen Inc. announced positive 12-month data from the phase 2 ArMaDa clinical trial evaluating OCU410 (AAV5-RORA), its novel modifier gene therapy for geographic atrophy (GA) secondary to dry AMD.⁴ The main findings were as follows:

• a 31% reduction in lesion growth in the optimal dose (medium) group compared to control (p < .05)

• a 27% slower rate of ellipsoid zone loss compared to the control, indicating structural preservation of photoreceptors, which correlates with visual function.

• 55% of treated patients demonstrated a 30% or greater lesion size reduction vs. the control.

• the subgroup analysis (subjects with baseline GA lesions ≥5 mm² and ≤17.5 mm²) showed a 33% reduction in lesion growth compared to the control in medium dose OCU410 with similar reductions in the high-dose group.

DME. The SPECTRA trial showed that 4D-150 is safe and effective for DME, with significant improvements in visual acuity and central subfield thickness. The trial showed no intraocular inflammation events, supporting the viability of this gene therapy approach.⁵

In the phase 3 COMO and CAPRI trials of DURAVYU(vorolanib intravitreal insert, EyePoint Pharmaceuticals) the first patients were dosed to treat DME. DURAVYU delivers a tyrosine kinase inhibitor targeting VEGF-mediated permeability, platelet-derived growth factor, and interleukin-6–mediated inflammation, with redosing every 6 months. The phase 3 results are expected to be announced in the second half of 2027.⁶

Retinitis pigmentosa (RP): In 2026, several promising gene therapies for RP progressed, spanning gene-agnostic optogenetics, modifier therapies, and mutation-specific replacement treatments. The notable developments this year include:

• MCO-010 (Nanoscope Therapeutics): This gene-agnostic optogenetic therapy showed lasting vision improvements in patients with advanced disease. MCO-010 yielded about 3 Early Treatment Diabetic Retinopathy Study-line best-corrected visual acuity improvements at 52 weeks and maintained gains to 152 weeks in the REMAIN study, supporting durable functional benefit in advanced RP.⁷

• OCU400 (Ocugen): In the phase 3 liMeliGhT for OCU400, a modifier gene therapy for RP, the disease was treated across multiple genetic subtypes by regulating retinal homeostasis. In 2026, Ocugen completed enrollment in the phase III trial and initiating rolling Biologics License Application submissions.⁸ Ocugen also signed an exclusive licensing agreement to expand the therapy's reach into the Middle East and North Africa.⁹

• FT-002 (Frontera Therapeutics): FT-002 showed safety and vision improvement in early-stage clinical trials for young male patients with X-linked RP. The treatment involves one subretinal injection that delivers a healthy version of the RPGR gene in a proprietary adeno-associated virus vector platform developed by Frontera Therapeutics, designed to efficiently target retinal photoreceptor cells and promote sustained expression of the therapeutic protein. Clinical trials show the therapy is highly safe, with no serious side effects or inflammation and participants experienced significant vision improvements that continued to increase during the follow-up period.¹⁰

• Botaretigene sparoparvovec (Bota-vec): This RPGR gene-targeted therapy achieved consistent vision improvements across secondary trial measures. In April 2026, MeiraGTx reacquired full rights to Bota-vec from Johnson & Johnson, despite missing the primary endpoint in the phase 3 LUMEOS trial. MeiraGTx plans to rapidly file for regulatory approval with the FDA and European regulators this year, targeting a potential commercial launch in 2027.¹¹

Stargardt disease: Caused by mutations in the ABCA4 gene, this leading cause of juvenile macular degeneration became a primary focus for advanced delivery platforms. Clinical trials evaluating dual-vector gene systems (eg, VeonGen and SpliceBio) advanced to address this large-genome packaging challenge.

• VG801 gene therapy: VeonGen Therapeutics presented highly promising phase 1/2 clinical trial results at the May 2026 annual meeting of the Association for Research in Vision and Ophthalmology. The trial showed consistent functional improvements in visual acuity without serious adverse events, securing the FDA's Regenerative Medicine Advanced Therapy designation.¹²

• SB-007: In January 2026, SpliceBio officially initiated the dose-expansion portion (part B) of their phase 1/2 ASTRA clinical trial for SB-007. This investigational, first-in-class dual-vector gene therapy targets the underlying cause of Stargardt disease.¹³

Corneal dystrophies: Gene editing made significant leaps as in vivo CRISPR-based therapeutics (like GEB-101 for TGFBI corneal dystrophy) achieved IND-clearance.

• GEB-101: GenEditBio received Investigational New Drug (IND) clearance to start an in vivo gene-editing trial targeting TGFBI corneal dystrophy in January 2026. This allowed the initiation of the phase 1/2 CLARITY trial to evaluate the safety and efficacy of the CRISPR-based gene therapy for corneal dystrophy associated with the TGFB1 gene.¹⁴

References

1. Foundation Fighting Blindness. 4DMT planning phase 3 clinical trial for wet AMD gene therapy. September 23, 2024. https://www.fightingblindness.org/news/4dmt-planning-phase-3-clinical-trial-for-wet-amd-gene-therapy-1168.

2. Harp MD. 4DMT completes enrollment in 4FRONT-2, global phase 3 trial of 4D-150 in wet AMD. Ophthalmology Times. June 30, 2026. https://www.ophthalmologytimes.com/view/4dmt-completes-enrollment-in-4front-2-global-phase-3-trial-of-4d-150-in-wet-amd.

3. Hoffman M. Is 2026 *Already* Redefining Eye Care's Clinical Development? https://www.linkedin.com/pulse/2026-already-redefining-eye-cares-clinical-matt-hoffman-g3lgf/.

4. Ocugen, Inc. Ocugen announces topline 12-month data from phase 2 Armada clinical trial evaluating ocu410 modifier gene therapy for geographic atrophy secondary to dry age-related macular degeneration. March 24, 2026; https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-topline-12-month-data-phase-2-armada-clinical/.

5. Loewenstein A, Do D. SPECTRA Data Support 4D-150 in DME. Retin Physician. June 17, 2026. https://www.retinalphysician.com/issues/2026/clinical-trials-at-the-summit/cts-spectra?d=report.

6. Harp MD. EyePoint doses first patient in COMO and CAPRI phase 3 trials of duravyu. Ophthalmology Times. March 2, 2026. https://www.ophthalmologytimes.com/view/eyepoint-doses-first-patient-in-phase-3-trials-como-and-capri.

7. Stevenson S. ARVO 2026: Gene therapy and optogenetics show lasting vision improvement in retinitis pigmentosa. Ophthalmology Times. May 5, 2026. https://www.ophthalmologytimes.com/view/arvo-2026-gene-therapy-and-optogenetics-show-lasting-vision-improvement-in-retinitis-pigmentosa.

8. Ocugen, Inc. Ocugen announces phase 3 limelight enrollment completion for ocu400, a novel modifier gene therapy for broad retinitis pigmentosa. March 2, 2026. https://ir.ocugen.com/news-releases/news-release-details/ocugen-announces-phase-3-limelight-enrollment-completion-ocu400/.

9. Ocugen, Inc. announces binding term sheet with Roots Pharmaceutical to license OCU400 modifier gene therapy for retinitis pigmentosa in the Middle East and North Africa. July 13, 2026; https://ir.ocugen.com/news-releases/news-release-details/ocugen-inc-announces-binding-term-sheet-roots-pharmaceutical/.

10. ARVO. https://www.arvo.org/news/first-in-human-gene-therapy-breakthroughs.

11. Foundation Fighting Blindness.MeiraGTx acquires XLRP gene therapy Bota-Vec, moves toward regulatory filing. April 16, 2026.

12. Foundation Fighting Blindness. VeonGen reports promising clinical progress for Stargardt Disease gene therapy. March 26, 2026. https://www.fightingblindness.org/news/veongen-reports-promising-clinical-progress-for-stargardt-disease-gene-therapy-3709.

13. SpliceBio press release. SpliceBio initiates dose-expansion portion of phase 1/2 ASTRA clinical trial for SB-007, a dual-AAV gene therapy for Stargardt Disease. January 8, 2026https://splice.bio/splicebio-initiates-dose-expansion-portion-of-phase-1-2-astra-for-sb-007/.

14. Charters L. Q1 2026 happenings in ophthalmology: Major highlights. Ophthalmology Times. March 27, 2026. https://www.ophthalmologytimes.com/view/q1-2026-happenings-in-ophthalmology-major-highlights.