In the latest episode of The Wills Retina Report, Regillo and Ho discuss where gene therapy stands for retinal disease, from late-stage programs in neovascular age-related macular degeneration to earlier efforts in geographic atrophy and diabetic retinopathy.
In this latest episode of The Wills Retina Report with Regillo and Garg from
Ho placed anti–VEGF gene therapy for nAMD and
The most advanced program, from REGENXBIO and AbbVie, delivers a next-generation adeno-associated virus 8 (AAV8) vector to the subretinal space to produce ranibizumab, Ho said. The pivotal ATMOSPHERE trial (NCT04704921)¹ compares it with ranibizumab, and ASCENT (NCT05407636)² compares it with aflibercept. Data from both are expected at the end of 2026, with regulatory activity in 2027, he said. REGENXBIO has reported that topline data from both trials are expected in the fourth quarter of 2026.³
Two in-office intravitreal programs follow. Adverum and Lilly’s program uses a next-generation 7M8 vector to produce aflibercept; Ho said data from ARTEMIS (NCT06856577)⁴ and AQUARIUS (NCT07482176)⁵ are expected to begin arriving in 2027. 4D Molecular Therapeutics (4DMT) began its pivotal trials in 2025, with data expected in 2027; the program uses the R100 directed-evolution vector carrying a dual transgene that includes an anti-VEGF-C component. The company has reported that enrollment in its first phase 3 trial, 4FRONT-1, is complete, with topline data expected in the second quarter of 2027.⁶
Ho cautioned that study populations differ. The REGENXBIO and AbbVie program enrolled higher-need, previously treated patients, whereas the intravitreal programs have moved toward including treatment-naive and previously treated patients, which makes cross-trial comparisons of reduced rescue injections imprecise. Regillo added that outcomes and the proportion of patients who are “one and done” could vary, though he did not expect them to be the majority in any program.
Programs for
Regillo noted that the therapeutic index for intravitreal delivery is narrow, because inflammation emerged as vector dose increased, and that the intravitreal programs require inflammation suppression after injection that the subretinal program does not. In the intravitreal programs, Ho said, inflammation has been mitigated by lowering the vector dose and extending topical steroids to about 6 months, which may or may not prove acceptable. Pigmentary changes have appeared across programs, he said, and subretinal delivery is now placed inferiorly to keep changes away from the macula. Subretinal eyes have been very quiet despite high vector doses, which Ho linked to the relative immune privilege of the subretinal space.
Ho predicted gene therapy will be in the retina toolkit around 2028 but will not replace intravitreal injections. He said he is most interested in whether steady-state delivery, rather than the bolus kinetics of injections, can provide better vision over time. Asked what share of his patients with maintenance-phase nAMD might choose gene therapy, Ho estimated less than 25%, citing patient, surgeon and payer considerations. He said he would offer it to some of his patients who need frequent injections.
