4D Molecular Therapeutics Announces FDA Clearance of IND Application for 4D-150, a Dual-Transgene Intravitreal Gene Therapy for Patients with wet AMD
October 06, 2021 at 07:30 am EDT
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4D Molecular Therapeutics announced that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug Application (IND) for 4D-150 for wet age-related macular degeneration (wet AMD). The active IND enables the initiation of 4D-150 Phase 1/2 clinical trial sites, which is expected before year-end. The Phase 1/2 clinical trial is a dose-escalation and randomized, controlled, masked expansion trial of intravitreal 4D-150 and is expected to enroll approximately 60 adults with wet AMD. In the dose-escalation phase, multiple dose levels of 4D-150 will be examined in an open-label, 3+3 design with an initial dose of 3E10 vg/eye. In dose expansion, patients (n=50) will be randomized 2:2:1 to receive one of 2 dose levels of 4D-150 (n=20 for each dose level) or aflibercept (n=10). The primary endpoints of the study are safety and tolerability. Secondary endpoints include the number of supplemental aflibercept injections received, and change from baseline in best corrected visual acuity (BCVA) over time. 4D-150 is a dual-transgene, intravitreal gene therapy designed to inhibit four distinct VEGF factors and prevent angiogenesis and vascular permeability for the treatment of wet AMD. The company believe that targeting four distinct angiogenic factors with dual transgenes in patients with these retinal diseases has the potential for greater efficacy and/or lower required doses versus therapies that target a single VEGF factor, including in patients refractory to currently approved anti-VEGF therapies. Intravitreal delivery of biologics to the eye is routine, and a single dose intravitreal gene therapy that could provide long-term efficacy in patients would be an advantage for patients who struggle with treatment burden and/or treatment resistance. 4D-150 builds on the excellent tolerability to date of the R100 capsid in the 4D-125 XLRP clinical program at doses up to 1E12 vg/eye. In the non-human primate retinal laser-induced CNV model data presented in May 2021 at the annual conference of the American Society of Gene and Cell Therapy, at doses ranging from 1E11 to 1E12 vg/eye, 4D-150 intravitreal injection resulted in 100% suppression of grade 4 angiogenic lesions. Wet AMD is a type of macular degeneration in which abnormal blood vessels grow into the macula and cause visual distortion, reduced acuity and, in some cases, blindness. The proliferation of abnormal blood vessels in the retina is stimulated by VEGF family members. There are approximately 200,000 new incidences of wet AMD per year in the United States alone. High expression levels of VEGF appear to play a causal role in the symptoms of wet AMD.
4D Molecular Therapeutics, Inc. is a clinical-stage genetic medicines company focused on unlocking the full potential of genetic medicines to treat diseases in ophthalmology and pulmonology. The Company has a portfolio of genetic medicine product candidates, with five product candidates in clinical trials in seven patient populations: 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), 4D-710 for the treatment of cystic fibrosis lung disease (both in modulator ineligible and eligible populations), 4D-310 for the treatment of Fabry disease cardiomyopathy, 4D-125 for the treatment of X-linked retinitis pigmentosa (XLRP), and 4D-110 for the treatment of choroideremia. In addition, it has two product candidates in preclinical development: 4D-175 for geographic atrophy (GA) and 4D-725 for alpha-1 antitrypsin deficiency lung disease.