APEX: A phase II randomised clinical trial evaluating the safety and preliminary efficacy of oral X-82 to treat exudative age-related macular degeneration

Michael N. Cohen, Denis O'Shaughnessy, Kate Fisher, Jennifer Cerami, Carl C. Awh, Daniel E. Salazar, Philip Rosenfeld, Jeffrey S. Heier

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose The safety and efficacy of X-82, an orally administered inhibitor of vascular endothelial growth factor (VEGF) and platelet-derived growth factor, was investigated for treatment of wet age-related macular degeneration (AMD) in a phase II clinical trial. Methods This phase II, randomised, double-masked, placebo-controlled trial enrolled subjects with a prior diagnosis of exudative AMD having received at least two intravitreal injections of anti-VEGF therapy. Subjects were randomised equally into four groups that received either daily 50mg, 100mg or 200mg dosages of X-82 or a placebo tablet. At each 4-week interval visit for 52 weeks, subjects were to be assessed to determine if rescue treatment was needed with anti-VEGF therapy. Results 157 patients were enrolled. Due to gastrointestinal and hepatobiliary adverse events and the fulfilment of the primary endpoint, the trial was stopped prematurely after a second interim analysis. The primary endpoint of non-inferiority of visual acuity compared with placebo was demonstrated in all groups receiving X-82 (p<0.001). There was a dose-dependent trend in the number of injections over a 52-week period, with the 50 mg (n=40), 100 mg (n=39), 200 mg (n=39) and placebo (n=39) group requiring 6.7, 6.0, 4.7 and 8.1 injections, respectively. Conclusions X-82 oral therapy in combination with pro re nata anti-VEGF injections showed non-inferiority in visual acuity outcomes while achieving a dose-dependent decrease in the number of anti-VEGF injections compared with placebo. Given the limited tolerability and safety issues observed, X-82 does not have a sufficient benefit to risk profile in treatment of patients with AMD.

Original languageEnglish (US)
Pages (from-to)716-722
Number of pages7
JournalBritish Journal of Ophthalmology
Volume105
Issue number5
DOIs
StatePublished - May 1 2021

Keywords

  • Angiogenesis
  • Choroid
  • Macula
  • Macular Degeneration
  • Retina
  • Vitreous
  • oral
  • randomized controlled trial

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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