Glaukos reports positive Phase 3 results for Epioxa

(Image credit: Adobe Stock/Fukume)

Glaukos Corp has reported positive results from its second Phase 3 confirmatory trial for Epioxa (Epi-on), the company’s next-generation corneal cross-linking iLink therapy for keratoconus. The trial successfully met its primary efficacy endpoint, marking a significant milestone for the treatment.

The study demonstrated a clinically meaningful and statistically significant improvement in maximum corneal curvature (Kmax) at 12 months compared to the sham/placebo-controlled arm, underscoring Epioxa's potential in managing keratoconus progression.

The company noted in a news release Kmax is an FDA-accepted primary efficacy outcome for keratoconus pivotal trials and an objective measurement of the steepest corneal curvature based on corneal topography, where an increasing Kmax denotes corneal steepening and keratoconus disease progression.¹

Thomas Burns, Glaukos chairman and CEO, said the company was pleased to unveil the 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.

“These results further underscore our view that Epioxa may provide the ophthalmic community and keratoconus patients with the first FDA-approved, non-invasive, bio-activated drug treatment alternative designed to reduce procedure time, improve patient comfort and shorten recovery time,” Burns said in the news release. “We appreciate the commitment and dedication of the clinical investigators, who play a vital role in bringing new innovations to patients suffering from keratoconus and at risk for significant vision loss. We expect these data to support our anticipated NDA targeted for FDA submission by the end of this year.”

Topline summary results and observations from the Phase 3 confirmatory pivotal trial are as follows:

• The Epioxa Phase 3 clinical trial successfully achieved its primary efficacy outcome by demonstrating a Kmax treatment effect of –1.0 diopter (D) (p <0.0001), determined as prospectively defined least square mean Kmax change from baseline in the Epioxa treated arm versus the sham/placebo-controlled arm at the Month 12 study endpoint.
• The treatment was generally well-tolerated, with 91.5% of enrolled treatment patients completing the 12-month trial, compared to 90.9% of enrolled control patients. No patients randomized to Epioxa treatment discontinued early due to an adverse event and there were no ocular serious adverse events reported.
• The majority of adverse events reported were mild and transient in nature. There was no evidence of treatment-related systemic effects reported in the study and there was no change in corneal endothelial cell counts over the 12-month evaluation period.¹

According to the company, the multi-center, randomized, placebo and sham controlled Phase 3 confirmatory pivotal trial randomized 312 eyes and was designed to evaluate the safety and efficacy of Glaukos’ Epioxa therapy in impeding the progression of, and/or reducing Kmax, in eyes with progressive keratoconus. The study eyes were randomized in a 2:1 ratio to receive Epioxa therapy or placebo and sham procedure control treatment.

Moreover, the study’s primary efficacy endpoint was the mean change in Kmax from baseline to Month 12. Based on a special protocol assessment (SPA) agreement with the U.S. FDA, the study was to be considered a success if the difference between the treatment and control arm in the primary efficacy endpoint is statistically significant and the difference is ≥ 1.0 D.¹

Results from this second Phase 3 confirmatory pivotal trial together with the already-completed first Phase 3 pivotal trial are expected to support Glaukos’ anticipated NDA submission for Epioxa by the end of 2024. As a reminder, the U.S. FDA has confirmed Glaukos’ first Phase 3 pivotal trial for Epioxa, which met the pre-specified primary efficacy endpoint, would be adequate to support the submission and review of an eventual NDA, in conjunction with this second Phase 3 trial.

According to the company, it recently completed a successful clinical pre-NDA meeting with the FDA regarding Epioxa as a novel treatment for keratoconus. The purpose of the meeting was to obtain agreement from the FDA on the content of the proposed NDA, and in particular, to confirm that the company’s clinical data package, including the two completed Phase 3 pivotal studies, would be sufficient to support an NDA submission and review. As an outcome of this pre-NDA meeting, the FDA agreed that the proposed clinical data package is sufficient to support an NDA submission and review.¹

Glaukos' iLink therapies use proprietary, bio-activated, single-use drug formulations to strengthen corneal tissue and halt the progression of keratoconus, a debilitating eye condition marked by the thinning and weakening of the cornea. Typically diagnosed during adolescence, keratoconus can lead to severe vision loss and is a leading cause of corneal transplants (penetrating keratoplasty) in the U.S. If left untreated, it can result in blindness, with approximately 90% of cases being bilateral and up to 20% of patients eventually requiring a corneal transplant. While conventional treatments like eyeglasses and contact lenses only address the symptoms, Glaukos' first-generation iLink therapy, Photrexa (Epi-off), is the only FDA-approved treatment proven to slow or halt disease progression. Its efficacy is supported by over 300 peer-reviewed publications.

Epioxa, Glaukos' next-generation therapy, is designed to preserve the corneal epithelium, reduce procedure times, enhance patient comfort, and shorten recovery. This novel formulation penetrates the corneal epithelial layer and utilizes a stronger UV-A irradiation protocol alongside increased supplemental oxygen to improve cross-linking. If approved, Epioxa would become the first FDA-approved non-invasive corneal cross-linking therapy that does not require removal of the corneal epithelium, offering a less invasive option for keratoconus treatment.

Reference:

1. Glaukos Announces Positive Topline Outcomes in Phase 3 Confirmatory Trial for Epioxa, Achieving Primary Efficacy Endpoint and Demonstrating Favorable Tolerability and Safety. Business Wire. Published October 16, 2024. Accessed October 16, 2024. https://www.businesswire.com/news/home/20241016373490/en/Glaukos-Announces-Positive-Topline-Outcomes-in-Phase-3-Confirmatory-Trial-for-Epioxa™-Achieving-Primary-Efficacy-Endpoint-and-Demonstrating-Favorable-Tolerability-and-Safety