Assessing the Safety and Efficacy of DS-7080a Versus Ranibizumab in Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema: A Phase I, Open-Label, Multicenter Study

<h2>Abstract</h2><h3>Purpose</h3> To evaluate the safety and efficacy of DS-7080a in eyes with neovascular age-related macular degeneration (nAMD) and diabetic macular edema (DME) alone or in combination with ranibizumab. <h3>Design</h3> This was a Phase I dose-escalation-and-expansion study registered on clinicaltrials.gov (NCT02530918) and conducted in three parts. Parts one (P1) and two (P2) involved dose-escalation-and-expansion for nAMD patients while Part three (P3) involved dose-expansion-only for DME subjects. <h3>Subjects</h3> Patients with nAMD or DME. <h3>Methods</h3> In P1, eligible patients were randomized into three sequential dose-level cohorts to establish a maximum tolerated dose (MTD) for DS-7080a as 4.0 mg and assess its safety and tolerability. The study then proceeded to P2 where 27 nAMD subjects were randomized to one of the three treatment arms: DS-7080a-4.0-mg-only, ranibizumab-0.5 mg-only, or DS-7080a-4.0-mg-plus-ranibizumab-0.5 mg. In P3, 20 subjects with DME were randomized to one of the two arms: DS-7080a-4.0-mg or ranibizumab-0.3-mg injected thrice. The treatment period was 12 weeks. <h3>Outcomes</h3> Primary endpoints were treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). Secondary endpoints were changes in central retinal thickness (CST) and best corrected visual acuity (BCVA). <h3>Results</h3> A total of 56 patients were enrolled. DS-7080a, administered as monotherapy or in combination with ranibizumab, was generally well tolerated. Six drug-related TEAEs were observed, four of which were ocular events that led to treatment discontinuation. No drug-related SAEs or deaths occurred. As expected, ranibizumab was associated with improvements in BCVA and CST, whereas DS-7080a, alone or in combination, did not show clinically meaningful functional or anatomical benefit. <h3>Conclusions</h3> DS-7080a was generally well tolerated in eyes with nAMD and DME; however, drug-related TEAEs, including ocular events leading to discontinuation, were observed. In terms of efficacy outcomes, DS-7080a does not show BCVA improvement and CST decrease when administered alone or in conjunction with ranibizumab. These findings are inconsistent with non-clinical studies supporting DS-7080a as a therapeutic agent for nAMD and DME.