Key Takeaways

  • Epion Therapeutics has completed all patient follow-up visits in its two pivotal phase 3 trials evaluating EpiSmart, an investigational epithelium-on corneal cross-linking procedure for keratoconus
  • The double-masked, sham-controlled studies enrolled approximately 800 patients across 26 U.S. sites, with BSCDVA at 12 months serving as the primary endpoint
  • Following data analysis, Epion plans to pursue FDA approval of EpiSmart

Epion Therapeutics announced that the final patient has completed the last study visit in the company's phase 3 clinical program evaluating EpiSmart, an epithelium-on corneal cross-linking procedure. The completion of all follow-up examinations across both pivotal trials concludes patient participation in the program and positions the company to advance toward a planned regulatory submission to the FDA.

The phase 3 program consists of two identical, double-masked, sham-controlled studies designed to evaluate the safety and efficacy of EpiSmart in patients with keratoconus. Initiated in October 2023, the trials enrolled approximately 800 patients at 26 clinical sites across the United States. Participants represented a broad spectrum of disease severity, ranging from early tomographic diagnosis to advanced progressive keratoconus.

Patients were randomized in a 1:1 ratio to receive either EpiSmart or a sham procedure. When clinically appropriate, simultaneous bilateral treatment was performed. Both studies were designed with Best Spectacle-Corrected Distance Visual Acuity (BSCDVA) at 12 months as the primary efficacy endpoint, emphasizing functional vision outcomes.

“We believe EpiSmart represents the next step in the evolution of cross-linking,” said Michael D. Webb, President and CEO of Epion Therapeutics. “The completion of our phase 3 program brings us one step closer to making EpiSmart available to keratoconus patients and all who care for them.”

Pending positive study outcomes and regulatory review, Epion plans to submit a new drug application (NDA) to the FDA seeking approval of EpiSmart in the US.

In October 2025, the FDA granted Fast Track designation to EpiSmart for the treatment of keratoconus. The designation is intended to facilitate development and expedite review of therapies that address serious conditions and unmet medical needs.

EpiSmart is designed as a minimally invasive corneal cross-linking system intended to strengthen the cornea while preserving the epithelial surface. The platform combines a proprietary ocular-surface cleansing wand that avoids epithelial disruption, a loading sponge designed to promote uniform stromal drug distribution, and a fixed-dose riboflavin and iodide formulation intended to enhance cross-linking efficiency without supplemental oxygen.

The system also incorporates what Epion describes as the first bilateral UV-A treatment device for corneal cross-linking. The device uses a proprietary light-cycling protocol designed to support oxygen re-diffusion during treatment, a factor believed to play a critical role in the cross-linking process.