Arshad Khanani, MD, on Reducing Treatment Burden in Wet AMD With Gene Therapy

“4D-150 is the first dual transgene therapy, it targets all the ligands of the angiogenesis pathway. So, our hope is that with 4150, we will be able to control wet AMD very well. It’s also exciting because it’s administered in clinic.”

New data from cohort 1 of the phase 1/2 PRISM trial (NCT05197270) has shown that the gene therapy 4D-150 (4D Molecular Therapeutics) restored aflibercept expression to therapeutic levels in 5 patients in with wet age-related macular degeneration (AMD). These participants each received a single intravitreal injection of 3E10 vg/eye of 4D-150.

Investigators found that participants had a 96.7% reduction in mean annualized anti-VEGF injection rate, from around 11 in the year prior to enrollment.Most participants (80%) did not receive any supplemental aflibercept injections for around 40, 36, 32, or 16 weeks after treatment. Therapeutic levels of aflibercept expression were found in the aqueous humor of the eye at 12 weeks after injection.

CGTLive spoke with principal investigator Arshad Khanani, MD, director, clinical research, and clinical associate professor, University of Nevada Reno School of Medicine, to learn more about the potential of gene therapy in wet AMD. He discussed unmet needs within the patient population of wet AMD, including treatment burden and patient compliance.

REFERENCE

4D Molecular Therapeutics announces interim clinical data from on-going phase 1/2 clinical trial of intravitreal 4D-150 for wet age-related macular degeneration (wet AMD). News release. 4D Molecular Therapeutics. November 14, 2022. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4d-molecular-therapeutics-announces-interim-clinical-data-going