Dr. Christine Kay
Credit: Atsena Therapeutics
Interim Results of Phase 1/2 PRISM Trial Show Investigational Single-Dose Intravitreal Genetic Agent 4D-150 Is Safe and Well-Tolerated Over a Range of Dosages in Patients with Neovascular Age-Related Macular Degeneration (nAMD) This suggests that the quality is good.1
Presented at the 41st Annual Meeting of the American Society of Retinal Surgeons (ASRS), this genetic medicine combines two transgenes encoding aflibercept and a miRNA sequence targeting vascular endothelial growth factor (VEGF)-C. It consisted of a retinal localized AAV vector (R100) carrying and was relevant. There was a clinically meaningful reduction in anti-VEGF treatment burden at all dose levels.
“No patients suffered intraocular hypotension, intraocular inflammation, no reinduction of topical steroids in 14 to 15 patients, an 81% reduction in annual injection-free interval in patients receiving intravitreal injections of 3E10 doses, We have a safe profile for gene therapy with 4D-150 vectors,” said Christine Kay, M.D., Ph.D., presenting investigator at Vitreo Retinal Associates, at ASRS 2023.
The 4D-150 vector is administered via a single intravitreal injection, allowing broad delivery to all layers of the retina and efficient depletion of retinal cells. The PRISM trial is a Phase 1/2 clinical trial evaluating the safety, tolerability and clinical efficacy of 4D-150, beginning with a dose-finding phase and moving into a dose-expansion phase.
Key inclusion criteria included patients age 50 years or older, choroidal neovascularization secondary to nAMD, visual acuity with ETDRS letters ≥25 and ≤78, clinical response to anti-VEGF within the previous 12 months, and 6 One or more anti-VEGF injections were included. . A total of 15 patients were enrolled in her three consecutive dose cohorts of 3E10, 1E10, and her 6E9 vg/eye. each n=5).
The primary endpoint was the incidence and severity of treatment emergent adverse events (TEAEs) and serious adverse events (SAEs). Key secondary endpoints included annual rate of change in anti-VEGF injection rate, proportion of subjects requiring booster doses of aflibercept, number of booster doses of aflibercept, change in BCVA from baseline, CST change from baseline was included. As of data cutoff on July 3, 2023, all patients had completed her ≥36 weeks of follow-up.
Upon analysis, the investigators found a dose response that supported the highest dose tested, 3E10 vg/eye, including a 100% reduction in additional anti-VEGF injections (4 of 4 evaluable patients had no injections). found what was shown. Furthermore, it was associated with a clinically meaningful reduction in mean CST at 36 weeks in patients with high anti-VEGF need.
Furthermore, evaluation of outcomes from week 36 onwards in the 3E10 vg/ocular dose cohort showed a sustained decline in anti-VEGF adjuvant injections, with 3 of 4 evaluable study participants receiving injections beyond 1 year. 1 patient remained without injections during the period. Up to 80 weeks follow-up. No change in safety profile was observed.
Analyzes showed that lower doses (1E10, 6E9 vs/eye) were also highly active, with 5 of 10 patients requiring 0 or 1 anti-VEGF booster injection, and 36 weeks.
Regarding safety, analysis showed that intravitreal 4D-150 remained well-tolerated at all doses in all patients, with no grade 1 or greater inflammatory cell, hypotonic, dose-limiting toxicities during 36-week follow-up. , or TEAEs were not observed. 4D-150 will continue to be studied in the Phase 2 PRISM trial in nAMD patients and the Phase 2 SPECTRA trial in DME patients.
“Favorable safety profile and continued clinical activity, including clinically meaningful reduction in anti-VEGF therapeutic burden at all dose levels of intravitreal 4D-150 in these advanced patients requiring anti-VEGF therapy We are pleased to have positive evidence,” said Dr. Robert Kim. 4DMT’s chief medical officer said in a statement.2 “Additionally, 3 of 4 evaluable patients in the 3E10 vg/eye cohort are now free of anti-VEGF injections after 1 year and have up to 80 weeks of follow-up, providing early promising evidence of long-term persistence. We will continue to follow these patients and look forward to presenting preliminary data for the first Phase 2 dose expansion in the first half of 2024.”
References
- Kay CN, Khanani AM, Hershberger VS, Hu A, Eichenbaum DA, Jaffe GJ, Chung C, Honarmand S, Nien C, Lee S, Kabra H, Kirn D, Kim R. Interim outcome evaluation of the phase 1/2 PRISM trial 4D-150, a dual transgene intravitreal genetic drug for neovascular (wet) age-related macular degeneration. Paper presentation at the 41st Annual Meeting of the American Association of Retinal Physicians. From July 28th to August 1st.
- 4DMT will present additional positive interim data from the intravitreal 4D-150 Phase 1/2 Prism clinical trial in WET AMD patients at ASRS 2023. 4D Molecular Therapeutics. July 29, 2023. Accessed 30 July 2023. https://ir.4dmoleculartherapeutics.com/news-releases/news-release-details/4dmt-presents-Additional-positive-interim-data-inravitreal-4d#top.
