FDA Accepts NDA for Epioxa for Keratoconus Treatment

Credit: US Food and Drug Administration

The US Food and Drug Administration (FDA) has accepted the New Drug Application (FDA) for Epioxa (Epi-on), a corneal cross-linking therapy for the treatment of keratoconus, a sight-threatening corneal disease.¹

Announced by Glaukos Corporation, on February 24, 2025, the FDA has set a Prescription Drug User Fee Act (PDUFA) target action date of October 20, 2025, to review the Epioxa NDA, reflecting a standard 10-month review period.

“The acceptance of the Epioxa NDA represents another important step in being able to provide keratoconus patients and the ophthalmic community with the first FDA-approved, non-invasive corneal cross-linking drug therapy that does not require removal of the corneal epithelium, the outermost layer of the front of the eye,” said Thomas Burns, chairman, and chief executive officer of Glaukos, in a statement.¹

As a progressive eye condition, keratoconus is characterized by progressive thinning and forward protrusion of the cornea, which can lead to notable visual impairment. The disorder is a leading indication for corneal transplantation in the US, with approximately 90% of cases being bilateral and up to 20% of patients ultimately requiring a transplant.

Initial treatment options for keratoconus typically involve prescription eyeglasses, contact lenses, and collagen cross-linking, which could slow or halt disease progression if administered early.² Glaukos’ first-generation iLink therapy, Photrexa (Epi-off), has been approved by the FDA to slow or halt the disease progression of keratoconus.

The company’s iLink therapies center on a proprietary, bio-activated drug formulation created to strengthen corneal tissue and impede the progression of keratoconus. Epioxa uses a novel drug formulation to penetrate the epithelial layer of the cornea, a strong UV-A irradiation protocol, and supplemental oxygen to intensify cross-linking.¹

Announced by Glaukos in December 2024, the NDA submission involved data from two Phase 3 pivotal trials of Epioxa. Epioxa met the pre-specified primary efficacy endpoint at the end of the second phase confirmatory pivotal trial, achieving a clinically relevant and statistically significant improvement in maximum corneal curvature (Kmax).³

The multi-center, randomized, placebo, and sham-controlled Phase 3 trial randomized 312 eyes in a 2:1 ratio to receive Epioxa or placebo and sham procedure control treatment. Based on a special protocol assessment (SPA) agreement with the FDA, success was defined as a statistically significant difference of ≥1.0 diopter (D) between treatment arms.

At the 12-month study endpoint, Epioxa demonstrated a Kmax treatment effect of –1.0 D (P <.0001), determined as a prospectively defined least square mean Kmax change from baseline versus the sham and placebo-controlled arm. The treatment was well-tolerated with 91.5% of enrolled treatment patients completing the 12-month trial, with the majority of adverse events mild and transient, without evidence of treatment-related systemic events.⁴

Pending approval from the FDA, Glaukos announced Epioxa could become the first non-invasive corneal cross-linking therapy that does not require the removal of the corneal epithelium.

“We look forward to working closely with the FDA throughout their review process and continue to believe Epioxa, which is designed to reduce procedure times, improve patient comfort, and shorten recovery times, represents a potentially meaningful advancement in the treatment paradigm for patients suffering from keratoconus,” Burns added.¹

References

1. Glaukos Announces FDA Acceptance of NDA Submission for EpioxaTM. Glaukos.com. February 24, 2025. Accessed February 24, 2025. https://investors.glaukos.com/investors/news/news-details/2025/Glaukos-Announces-FDA-Acceptance-of-NDA-Submission-for-Epioxa/default.aspx.

2. Asimellis G, Kaufman EJ. Keratoconus. [Updated 2024 Apr 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK470435/

3. Glaukos Submits New Drug Application to U.S. FDA for EpioxaTM. Glaukos.com. December 23, 2024. Accessed February 24, 2025. https://investors.glaukos.com/investors/news/news-details/2024/Glaukos-Submits-New-Drug-Application-to-U.S.-FDA-for-Epioxa/default.aspx.

4. Glaukos Announces Positive Topline Outcomes in Phase 3 Confirmatory Trial for EpioxaTM, Achieving Primary Efficacy Endpoint and Demonstrating Favorable Tolerability and Safety. Glaukos.com. October 16, 2024. Accessed February 24, 2025. https://investors.glaukos.com/investors/news/news-details/2024/Glaukos-Announces-Positive-Topline-Outcomes-in-Phase-3-Confirmatory-Trial-for-Epioxa-Achieving-Primary-Efficacy-Endpoint-and-Demonstrating-Favorable-Tolerability-and-Safety/default.aspx.