Two-Year PRISM Data Show Reduced Treatment Burden

Clinical Report: Two-Year PRISM Data Show Reduced Treatment Burden

Overview

At the 2026 AAO meeting, Veeral Sheth, MD, described two-year phase 1/2 PRISM data for intravitreal 4D-150 in neovascular age-related macular degeneration (AMD). He reported stable central subfield thickness (CST) and best-corrected visual acuity (BCVA), alongside fewer supplemental injections, with treatment needs varying by patient subgroup.

Background

Neovascular AMD is treated with intravitreal anti-VEGF therapy, identified as standard of care in the American Academy of Ophthalmology’s 2025 Preferred Practice Pattern. 4D-150 is an investigational intravitreal gene therapy being evaluated for its potential to provide durable treatment effects. The PRISM program has assessed the therapy in patients with wet AMD, and the interview reports two-year phase 1/2 findings. The source describes topical steroid use to address inflammation in the trial and planned phase 3 study.

Data Highlights

Patient subgroup	No supplemental injections over 2 years	Two or fewer supplemental injections over 2 years
Recalcitrant patients, previously treated almost monthly	22%	Close to 59%
More recently diagnosed patients	66%	Close to 90%

Sheth also reported stable CST and BCVA at two years. The interview did not provide numerical CST or BCVA results.

Key Findings

Two-year phase 1/2 PRISM data were reported for intravitreal 4D-150 in neovascular AMD.
Sheth described CST and BCVA as stable over the reported follow-up period.
Among recalcitrant patients who had received almost monthly treatment before trial entry, 22% received no injections during the two-year period.
Close to 59% of recalcitrant patients required two or fewer supplemental treatments over two years.
Among more recently diagnosed patients, 66% required no supplemental treatment and close to 90% required two or fewer injections over two years.
Sheth said the trial and phase 3 study would use topical steroids for 20 weeks, with the aim of blunting inflammation and tapering the drops over that period.

Clinical Implications

The interview reports that supplemental injection requirements differed between recalcitrant and more recently diagnosed patients, so the findings do not support describing treatment as uniformly “one and done.” Sheth stated that topical steroids would be used for 20 weeks in the trial and phase 3 study; the source does not provide further safety outcomes.

Conclusion

The two-year PRISM update described stable CST and BCVA alongside reduced supplemental injection requirements in both reported patient subgroups. The findings are from a phase 1/2 program, and the interview notes that phase 3 enrollment is forthcoming.