Abstract
Purpose :
Phosphatidylserine (PS) is a cell membrane lipid implicated in the pathophysiology of RVO, DMR and AMD. In RVO patients, PS is exposed on circulating RBCs and contributes to their adhesive properties to microvascular endothelium, a feature implied as causative. ANXV, a recombinant human Annexin A5 protein, inhibits PS and acts as an anti-inflammatory, cell protective and anti-adhesive agent. A Phase 2a study with ANXV in RVO is currently ongoing and early findings are reported.
Methods :
All treatment-naive early onset RVO patients are eligible (see Study Details | Safety and Proof of Concept Study of ANXV (Annexin A5) in Patients With Retinal Vein Occlusion | ClinicalTrials.gov). Following a protocol amendment, it is an open-label dose-escalation study with ANXV administered as flat doses of 2 mg or 4 mg by 30 min i.v. infusions for 5 days. Patients are followed for AEs, safety labs, PK, ADA, ophthalmic assessments and requirement of anti-VEGF. Inclusions of 6 patients on 2 mg, up to 10 patients on 4 mg and 6 mg are planned.
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Results :
Up to date, six RVO patients have been treated with 2 mg ANXV and two with 4 mg and followed for between 4 weeks and 12 months post treatment. No SAEs, AESIs, clinically significant lab parameter changes or ADA have been reported. Three ANXV-treated patients, one with ischemic BRVO, one with HRVO and one with ischemic CRVO have shown BCVA improvements (15 letters, 7 letters and 11 letters respectively). CST changes and indications of improved circulation on UW FA and OCTA at day 29 (i.e. 24 days after the last ANXV infusion). The first two patients received a single injection of anti-VEGF at Day 36. These patients have not required additional injections of anti-VEGF when followed up to date for 12 and 7 months, respectively, with maintained stable BCVA and dry macula. Two ANXV treated patients (CRVO) have not shown corresponding improvements. Two patients have been treated with ANXV in the month before abstract submission and ongoing evaluations will be reported.
Conclusions :
Based on a limited number of patients, safety and tolerability of 2 and 4 mg ANXV i.v. for 5 days appears acceptable. Improvements have been reported before anti-VEGF treatment and an atypical low requirement of anti-VEGF for up to 12 months post-ANXV have been observed. Safety and effect signal data support a continuation of the study.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.