Q&A: Christine Kay, MD, gives an investigator's perspective on the PRISM clinical trial

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At the 2025 Association for Research in Vision and Ophthalmology (ARVO) annual meeting, Christine Kay, MD, of Vitreoretinal Associates in Gainesville, Florida, shared an update from the PRISM clinical trial. Dr. Kay is a vitreoretinal surgeon and inherited retinal disease specialist. She is actively involved as an investigator in multiple clinical trials at Vitreo Retinal Associates, and presented data on behalf of 4D Molecular Therapeutics (4DMT).

Note: This conversation has been lightly edited for clarity.

Ophthalmology Times: You are presenting here at ARVO 2025 in Salt Lake City, Utah. Can you share with us what you will be presenting at this meeting?

Christine Kay, MD: I'm happy to be here at ARVO in Salt Lake City 2025 presenting on behalf of 4D Molecular Therapeutics (4DMT), the PRISM trial, which is a phase 1/2 clinical trial looking at a gene therapy for wet macular degeneration. 4D Molecular Therapeutics is a biotech company looking at developing novel gene therapies for retinal diseases.

OT: For this trial and research, can you share more about the candidate that was being evaluated?

Kay: The 4D-150 vector is designed for intravitreal injection, single delivery, and it is optimized for intravitreal injection with specific retinal tropism, meaning increased transduction to retinal cells, and also optimized to be able to invade the vitreoretinal barricades. The 4D-150 cassette is a dual vector, dual transgene cassette encoding both aflibercept as well as a micro-mRNA sequence inhibiting VEGF-C.

OT: What were some of the key data that resulted from the PRISM trial?

Kay: The PRISM trial is a phase 1/2 investigational clinical trial evaluating a single intravitreal injection of 4D-150 in patients with exudative macular degeneration. I presented here at ARVO an update, interim update on the phase 2b population extension study, which looked at patients both with severe disease as well as those more recently diagnosed with less severe disease. In summary, the patients had a stable visual acuity outcome at their 52 weeks, with stable retinal anatomy as well, as importantly, a decreased burden of treatment necessity. In fact, of the recently diagnosed patients, 80 percent of patients did not require supplemental injection out to 52 weeks, that was after 1 injection of 4D-150 gene therapy. If you were to translate that to comparing to EYLEA every 8 weeks, that would be a 94 percent treatment reduction compared to Q8 weeks EYLEA, which will be the comparator arm, and the ongoing phase 3 for 4D-150 looking at wet AMD. Importantly, from a safety standpoint, the inflammatory profile was excellent: 99 percent of patients were able to be tapered off their steroid protocol as per the protocol. And there were no events of 4D-150 related hypotony, choroidal effusions, endophthalmitis, [or] retinal occlusive vasculitis.