Glaukos Corporation announced that the second phase 3 confirmatory pivotal trial for Epioxa (Epi-on), its next-generation corneal cross-linking iLink therapy for the treatment of keratoconus, successfully met the study’s pre-specified primary efficacy endpoint, demonstrating a clinically relevant and statistically significant improvement in maximum corneal curvature (Kmax) at 12 months from baseline between the Epioxa treated arm and the sham/placebo-controlled arm.
Kmax is a U.S. 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.
“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. 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,” said Thomas Burns, Glaukos chairman and CEO. “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.
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.
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.
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 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.
Glaukos recently completed a successful clinical pre-NDA meeting with the U.S. 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.
Glaukos’ corneal cross-linking iLink therapies use proprietary, bio-activated, single-use drug formulations to strengthen corneal tissue and halt progression of keratoconus.
Typically diagnosed in a patient’s teenage years, keratoconus is a debilitating eye condition characterized by progressive thinning and weakening of the cornea. If left untreated, keratoconus can lead to loss of vision and even blindness and is one of the leading causes of corneal transplant (penetrating keratoplasty) in the United States. Approximately 90% of cases of keratoconus are bilateral and as many as 20% of patients ultimately require a corneal transplant.
Conventional keratoconus treatments such as eyeglasses or contact lenses address symptoms but Glaukos’ first-generation iLink therapy, known as Photrexa, or Epi-off, is the first and only FDA-approved therapy that has been shown to slow or halt disease progression. There are more than 300 peer-reviewed publications supporting the performance and safety of Glaukos’ iLink therapy.
Epioxa, which is designed to preserve the corneal epithelium, reduce procedure times, improve patient comfort and shorten recovery time, utilizes a proprietary, novel drug formulation designed to penetrate the epithelial layer of the cornea, a stronger UV-A irradiation protocol and the ability to deliver increased levels of supplemental oxygen to enhance cross-linking.
If approved, the company anticipates Epioxa would be the first FDA-approved, non-invasive corneal cross-linking therapy that does not require removal of the corneal epithelium, the outermost layer of the front of the eye.