Arshad Khanani, MD, on Future Plans for anti-VEGF Gene Therapy 4D-150


The director of clinical research at Sierra Eye Associates discussed 4D Molecular Therapeutics’ plans for 4D-150 in both wet AMD and diabetic macular edema.

“Whenever you have a first-in-human trial, you enroll patients that are very high-need and very difficult to treat. I'm looking forward to the phase 2 [study], where we have increased the lower limit of the visual acuity as well as the higher limit [in the trial’s enrollment criteria]. I would like to see how 4D-150 works in patients with less severe disease as well as shorter duration of disease. But obviously, if it's working well in the high-need chronic patients, we expect it to have meaningful efficacy in patients with better visual acuity and shorter disease duration.”

4D Molecular Therapeutics’ 4D-150 is an investigational gene therapy currently being evaluated in the phase 1/2 PRISM clinical trial (NCT05197270) for the treatment of wet age-related macular degeneration (AMD). The company expects that the gene therapy could provide a 1-time treatment option for patients with wet AMD. Currently, patients with this condition sometimes require injections of aflibercept (Eylea; Regeneron), a marketed antivascular endothelial growth factor (VEGF) product, every 4 to 8 weeks to prevent degeneration of their vision.

Arshad Khanani, MD, MA, FASRS, the director of clinical research and director of fellowship at Sierra Eye Associates, gave an oral presentation entitled, “Interim results for the phase 1/2 PRISM trial evaluating 4D-150, a dual-transgene intravitreal genetic medicine in individuals with neovascular (wet) age-related macular degeneration,” at the Association for Research in Vision and Ophthalmology (ARVO) 2023 Annual Meeting, held April 23-27, 2023, in New Orleans, Louisiana. The presentation covered the current data on the therapy to date that suggest a dose response in favor of the high dose (3x1010 vg/eye), with reductions observed in supplemental anti-VEGF injections and in mean central subfield thickness.

In an interview with CGTLive™, Khanani discussed the future plans for 4D-150 now that the dose exploration portion of the PRISM trial is completed. He spoke about the dose expansion plans, which include an aflibercept control arm. Khanani noted that if consistent safety and efficacy data is observed in this portion, the company will seek to initiate a pivotal trial for the gene therapy in wet AMD. He also mentioned that 4D Molecular Therapeutics is planning to initiate a separate phase 2 clinical trial, SPECTRA (NCT identifier pending), evaluating 4D-150 for the treatment of patients with diabetic macular edema.

Click here for more coverage of ARVO 2023.

1. 4DMT Presents Positive Interim Data from Intravitreal 4D-150 Phase 1/2 PRISM Clinical Trial in Patients with Wet AMD at ARVO 2023. News release. 4D Molecular Therapeutics. April 27, 2023. Accessed May 8, 2023.
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