According to the company, 4D-150 comprises its customized and evolved intravitreal vector, R100, and a transgene cassette that expresses both aflibercept and a VEGF-C inhibitory RNAi.
4D Molecular Therapeutics announced the first patient has been enrolled in the Dose Confirmation stage of the Phase 2 SPECTRA clinical trial (NCT05930561) evaluating intravitreal 4D-150 in patients with diabetic macular edema (DME), and that a Population Extension cohort has been added to the 4D-150 Phase 2 stage of the PRISM clinical trial (NCT05197270) in wet age-related macular degeneration (wet AMD).
Robert Kim, MD, chief medical officer of 4DMT, said in a news release the company is pleased to be advancing 4D-150 in its Phase 2 SPECTRA clinical trial in patients with DME and to further study intravitreal 4D-150 in a broader patient population in wet AMD.
“DME is a major cause of vision loss among people with diabetes and may lead to blindness,” he said in a news release. “Anti-VEGF agents are considered the mainstay of therapy for DME, yet the treatment burden with the current standard of care remains high.”
Based on its unique, multitargeted inhibition of four VEGF family members and the favorable clinical profile observed to date in the Phase 1/2 trial in wet AMD,” Kim said in the release 4D-150 has the potential to provide durable suppression of key pathogenic mediators in DME following a single intravitreal injection that can be administered in-office.
“In wet AMD, we believe that by expanding the patient population treated with 4D-150, we will further characterize 4D-150 in advance of our planned Phase 3 clinical trials, while taking advantage of strong enrollment momentum at clinical sites to date,” Kim said in the release.
David Kirn, MD, co-founder and CEO of 4DMT,noted in the release the continued rapid advancement of 4D-150 in DME and wet AMD demonstrates our commitment to large-market ophthalmology genetic medicines for patients in need, and shows physicians’ and patients’ interest in the transformative potential of single dose intravitreal 4D-150.
“DME is an important opportunity for 4DMT, and we believe 4D-150’s differentiated profile in wet AMD will drive interest and strong enrollment in the SPECTRA trial,” Kirn said in the release. “In wet AMD, 4D-150’s promising clinical profile to date in patients with the highest anti-VEGF need has enabled us to expand the PRISM trial to include a broader patient population in the Population Extension cohort. Importantly, we intend to include a broad wet AMD patient population in pivotal Phase 3 clinical trials with 4D-150. We look forward to sharing multiple clinical and regulatory milestones for 4D-150 in 2024.”
The trial is a multicenter, randomized, active-controlled, double-masked dose-ranging trial to evaluate the safety and efficacy of intravitreal 4D-150 in adults with DME and consists of 2 stages:
Key enrollment criteria includes:
While the key endpoints are:
The open-label trial is evaluating intravitreal 4D-150 3E10 and 1E10 vg/eye dose levels in patients with wet AMD.
Key enrollment criteria:
According to the news release, 4D-150 comprises our customized and evolved intravitreal vector, R100, and a transgene cassette that expresses both aflibercept and a VEGF-C inhibitory RNAi. The company. Noted this dual-transgene payload inhibits 4 angiogenic factors that drive wet AMD and DME: VEGF A, B, C and PlGF.
Moreover, the company also noted R100 was invented at 4DMT through our proprietary Therapeutic Vector Evolution platform; we created this platform utilizing principles of directed evolution, a Nobel Prize-winning technology. 4D-150 is designed for single, low-dose intravitreal delivery.