Glaukos Corporation's Epioxa (Epi-on), a next-generation corneal cross-linking iLink therapy, has demonstrated positive topline outcomes in its second Phase 3 confirmatory trial for the treatment of keratoconus. The study met its pre-specified primary efficacy endpoint, showing a clinically relevant and statistically significant improvement in maximum corneal curvature (Kmax) at 12 months from baseline compared to a sham/placebo-controlled arm.
Phase 3 Trial Results
The multi-center, randomized, placebo and sham-controlled trial involved 312 eyes with progressive keratoconus, randomized in a 2:1 ratio to receive either Epioxa therapy or a placebo/sham procedure. The primary efficacy endpoint was the mean change in Kmax from baseline to Month 12. The trial achieved a Kmax treatment effect of -1.0 diopter (D) (p < 0.0001), meeting the pre-defined success criteria based on a special protocol assessment (SPA) agreement with the FDA.
Thomas Burns, Glaukos chairman and chief executive officer, stated, "We are excited to announce these positive Phase 3 confirmatory results that met the study’s primary efficacy endpoint and once again demonstrated the potential of Epioxa to halt or reduce the advancement of keratoconus, a progressive, sight-threatening corneal disease."
Safety and Tolerability
The Epioxa treatment was generally well-tolerated. 91.5% of patients in the treatment arm completed the 12-month trial, compared to 90.9% in the control arm. There were no discontinuations due to treatment-emergent adverse events in the Epioxa arm, and no ocular serious adverse events were reported. The majority of adverse events were mild and transient. Glaukos reported no evidence of treatment-related systemic effects and no change in corneal endothelial cell counts over the 12-month evaluation period.
Regulatory Pathway
Glaukos intends to file a New Drug Application (NDA) with the FDA by the end of the year, supported by the results of this Phase 3 trial and a previously completed Phase 3 pivotal trial. The FDA has confirmed that the first Phase 3 trial, which also met its primary efficacy endpoint, is adequate to support the NDA submission in conjunction with the new data. Glaukos recently completed a successful pre-NDA meeting with the FDA, where the agency agreed that the proposed clinical data package is sufficient to support an NDA submission and review.
About Keratoconus and Epioxa
Keratoconus is a debilitating eye condition characterized by progressive thinning and weakening of the cornea, often diagnosed in a patient’s teenage years. If untreated, it can lead to significant vision loss and may require a corneal transplant. Approximately 90% of cases are bilateral, and up to 20% of patients may ultimately need a corneal transplant.
Epioxa is designed to strengthen corneal tissue and halt the progression of keratoconus. It utilizes a proprietary drug formulation to penetrate the epithelial layer of the cornea, combined with a stronger UV-A irradiation protocol and increased levels of supplemental oxygen to enhance cross-linking. Unlike Glaukos' existing FDA-approved iLink therapy, Photrexa, Epioxa does not require the removal of the corneal epithelium, potentially reducing procedure time and improving patient comfort.
Current Treatment Landscape
Conventional treatments for keratoconus, such as eyeglasses or contact lenses, primarily address the symptoms. Photrexa, Glaukos’ first-generation iLink therapy, is currently the only FDA-approved therapy shown to slow or halt disease progression. Epioxa aims to provide a less invasive alternative with potentially improved outcomes.
If approved, Epioxa could become the first FDA-approved, non-invasive corneal cross-linking therapy that does not require removal of the corneal epithelium, offering a significant advancement in the treatment of keratoconus.
