Glaukos Reports Positive Three-Year Phase 3 Extension Results for Epioxa in Keratoconus
Glaukos Corporation (NYSE: GKOS), an ophthalmic pharmaceutical and medical technology company developing innovative therapies for glaucoma, corneal disorders and retinal diseases, has announced positive topline results from a long-term Phase 3 extension study evaluating the durability, visual outcomes and safety of Epioxa®, its novel epi-on corneal cross-linking therapy for keratoconus.
The results from the three-year extension study, designated GLK-202-03, provide additional evidence supporting the potential of Epioxa to deliver durable disease stabilization following a single treatment. The study followed patients who had previously participated in Glaukos’ second Phase 3 pivotal trial, GLK-202-02, and assessed their outcomes for up to three years after receiving corneal cross-linking treatment.
Keratoconus is a progressive and potentially sight-threatening disorder in which the cornea, the transparent tissue at the front of the eye, gradually becomes thinner and changes shape. As the cornea becomes increasingly irregular and cone-shaped, patients can experience worsening vision, blurred or distorted sight and increasing difficulty achieving adequate vision correction with conventional lenses. Despite its potential impact on vision, keratoconus remains substantially undiagnosed and undertreated.
The latest long-term findings are therefore significant because they indicate that Epioxa may provide sustained structural and visual benefits without requiring additional intervention during the three-year extension period.
Sustained Corneal Flattening Through Three Years
According to Glaukos, eyes treated with Epioxa maintained a substantial improvement in maximum corneal curvature, or Kmax, through three years following treatment.
At year three, treated eyes demonstrated a sustained 1.9 diopter (D) improvement in Kmax from baseline. Kmax is an important clinical measure used in the assessment of keratoconus because it reflects the steepest point of the cornea. A reduction in maximum corneal curvature can indicate flattening and stabilization of the corneal shape, both of which are important objectives when treating progressive keratoconus.
The durability of the Kmax improvement through three years is particularly relevant to the potential clinical value of Epioxa. Rather than demonstrating an initial treatment effect that subsequently diminishes, the long-term extension data showed that the corneal flattening observed after treatment was sustained over the follow-up period.
For patients with a progressive corneal disorder, durable stabilization can be an important consideration because ongoing disease progression may lead to worsening visual quality and, in more advanced cases, the need for more invasive interventions.
The three-year data therefore add to the body of evidence supporting Epioxa as a potential long-term treatment option for patients with keratoconus.
Clinically Meaningful Improvements in Visual Acuity
In addition to the structural improvements measured through Kmax, the GLK-202-03 study demonstrated meaningful visual outcomes at the three-year assessment.
Glaukos reported that 29% of treated eyes gained two or more lines of best-corrected visual acuity from baseline, while 20% gained three or more lines.
Best-corrected visual acuity is a key measure of how well a patient can see when the eye is corrected using the best available vision correction. Improvements in this measure can provide an important indication that structural changes in the cornea are translating into meaningful benefits for patients.
The visual acuity findings are particularly notable in the context of keratoconus, where irregular corneal curvature can significantly affect visual quality. Stabilizing the cornea while also supporting improved visual performance could potentially help reduce the impact of the disease on daily activities and quality of life.
Together, the sustained Kmax improvement and visual acuity gains provide complementary evidence of Epioxa’s long-term clinical performance.
Favorable Long-Term Safety Profile
The three-year extension study also produced encouraging safety findings.
Glaukos reported that treated eyes maintained a favorable long-term safety profile through the three-year follow-up period. Importantly, there were no serious adverse events, no treatment-related adverse events and no discontinuations due to adverse events during the extension period.
The absence of these events in the reported long-term follow-up supports the company’s view that Epioxa may offer a favorable safety profile alongside its durability and visual outcomes.
Long-term safety is an important consideration for corneal cross-linking therapies because patients and physicians need to weigh the potential benefits of disease stabilization against procedural risks and recovery requirements. The three-year findings from GLK-202-03 provide additional information on the safety of Epioxa following a single treatment.
The extension study also did not involve additional intervention during the follow-up period, allowing investigators to evaluate the persistence of the original treatment effect over time.
Phase 3 Extension Study Design
GLK-202-03 was designed as a long-term extension study to assess safety, durability and clinical outcomes among patients who had completed Glaukos’ Phase 3 GLK-202-02 pivotal study and received corneal cross-linking treatment during the initial trial.
A total of 38 study eyes from 35 subjects participated in the extension study. Patients were followed for up to three years after treatment, with efficacy assessments focusing primarily on changes in corneal curvature and visual acuity.
Patient retention at the long-term assessment was also strong, with 92% of study eyes completing the year-three visit.
The extension design provides an opportunity to evaluate whether the treatment effects observed during the pivotal development program persist beyond the initial follow-up period. For a chronic, progressive disease such as keratoconus, long-term durability is an important component of the overall clinical profile of a potential treatment.
The latest findings suggest that a single Epioxa treatment can provide sustained corneal stabilization and meaningful visual benefits through three years, while maintaining a favorable safety profile.
Epioxa Takes an Epi-On Approach to Corneal Cross-Linking
Epioxa is being developed as an innovative approach to corneal cross-linking for keratoconus. One of its distinguishing characteristics is its epi-on treatment approach.
Traditional corneal cross-linking procedures generally involve removal of the corneal epithelium, the outermost layer of the cornea, to facilitate delivery of the treatment to the underlying corneal tissue. While established cross-linking approaches can help stabilize the cornea, epithelial removal can contribute to pain, discomfort and a recovery period following the procedure.
Epioxa is designed to provide an alternative that does not require removal of the corneal epithelium.
The therapy is an oxygen-supplemented topical therapeutic that is bioactivated by pulsed ultraviolet (UV) light. This approach is intended to facilitate corneal cross-linking while preserving the epithelial layer.
By eliminating the need for an incision or epithelial removal, Glaukos believes Epioxa could potentially streamline the treatment experience and reduce some of the discomfort and recovery burden associated with conventional approaches.
The company describes Epioxa as an incision-free treatment designed to minimize pain associated with epithelial removal, simplify the procedure and shorten recovery while maintaining robust and durable clinical outcomes.
Potential Significance for Keratoconus Patients
Keratoconus can have a substantial impact on vision, particularly when the disease progresses and the cornea becomes increasingly irregular. Treatment strategies that can slow or stabilize disease progression are therefore an important part of preserving visual function.
The long-term GLK-202-03 results are significant because they extend the available clinical evidence beyond the initial pivotal study period. Demonstrating sustained corneal flattening three years after a single treatment may be particularly relevant to patients and physicians seeking therapies that can provide lasting disease control.
The visual acuity findings further strengthen the potential clinical relevance of the treatment. Nearly three in ten treated eyes gained at least two lines of best-corrected visual acuity, while one in five gained at least three lines from baseline at year three.
These outcomes, combined with the absence of reported serious or treatment-related adverse events in the extension period, contribute to a broader assessment of Epioxa’s potential benefit-risk profile.
Glaukos Views Results as Support for a New Treatment Paradigm
Thomas Burns, chairman and chief executive officer of Glaukos, said the long-term findings further reinforce the potential of Epioxa to deliver durable benefits to people living with keratoconus.
He highlighted the sustained improvements in both corneal shape and visual acuity, along with what the company described as an excellent long-term safety profile.
The findings represent another step in Glaukos’ broader effort to develop therapies that address unmet needs in ophthalmology. The company has built its portfolio around pharmaceutical and medical technology approaches for diseases affecting different parts of the eye, including glaucoma, corneal disorders and retinal conditions.
For keratoconus specifically, the development of an epi-on cross-linking therapy could potentially broaden treatment options by offering an approach that does not require epithelial removal.
Three-Year Data Strengthen Epioxa’s Development Program
The positive topline results from GLK-202-03 provide important long-term data following Glaukos’ Phase 3 development of Epioxa. The sustained 1.9 D reduction in Kmax, visual acuity improvements and favorable safety results collectively indicate that the effects of a single treatment can persist for at least three years in the evaluated patient population.
The fact that 92% of treated eyes completed the year-three assessment also provides a meaningful level of long-term follow-up for the extension cohort.
While additional clinical and regulatory milestones will determine the future availability and use of Epioxa, the latest results add to the evidence supporting the therapy’s potential as a new approach to corneal cross-linking.
Glaukos believes the combination of an epi-on, incision-free treatment approach, durable corneal stabilization, clinically meaningful visual outcomes and favorable long-term safety could make Epioxa an important advancement in keratoconus management.
The company is continuing to advance Epioxa as part of its ophthalmic innovation strategy, with the latest three-year data offering further support for the therapy’s potential to address the needs of patients with a disease that remains significantly underdiagnosed and undertreated.
For additional information about Epioxa HD and Epioxa, including prescribing information, Glaukos directs healthcare professionals and other interested parties to the product’s official information resources.
About Glaukos
Glaukos (www.glaukos.com) is an ophthalmic pharmaceutical and medical technology company focused on developing and commercializing novel therapies for the treatment of glaucoma, corneal disorders, and retinal diseases. Glaukos first developed Micro-Invasive Glaucoma Surgery (MIGS) as an alternative to the traditional glaucoma treatment paradigm, launching its first MIGS device commercially in 2012.
In 2024, Glaukos commenced commercial launch activities for iDose® TR, a first-of-its-kind, long-duration, intracameral procedural pharmaceutical designed to deliver 24/7 glaucoma drug therapy inside the eye for extended periods of time. Glaukos also markets the only FDA-approved corneal cross-linking therapy utilizing a proprietary bio-activated pharmaceutical for the treatment of keratoconus, a rare corneal disorder.
Glaukos continues to successfully develop and advance a robust pipeline of novel, dropless platform technologies designed to meaningfully advance the standard of care and improve outcomes for patients suffering from chronic eye diseases.
About Epioxa HD / Epioxa
Indication: EPIOXA HD (riboflavin 5’-phosphate ophthalmic solution) 0.239% and EPIOXA (riboflavin 5’-phosphate ophthalmic solution) 0.177% are photoenhancers indicated for use in epithelium-on corneal collagen cross-linking for the treatment of keratoconus in adults and pediatric patients aged 13 years and older, in conjunction with the O2n® System and the Boost Goggles®.
Dosage and Administration: EPIOXA HD and EPIOXA are for topical ophthalmic use. NOT for injection or intraocular use. EPIOXA HD and EPIOXA are supplied in single-dose syringes. Discard opened syringes after use. EPIOXA HD and EPIOXA are for use with the O2n System and Boost Goggles only. Refer to the O2n System Operator’s Manual and Boost Goggles User Guide for device instructions.
Contraindications: EPIOXA HD and EPIOXA are contraindicated in patients with known hypersensitivity to benzalkonium chloride or any ingredients in EPIOXA HD and EPIOXA. Epithelium-on corneal collagen cross-linking is contraindicated in aphakic and pseudophakic patients without a UV-blocking intraocular lens.
Warnings and Precautions: Corneal collagen cross-linking should be used with caution in patients with a history of herpetic keratitis due to the potential for reactivation of herpes keratitis.
Adverse Reactions:The most common adverse reaction was conjunctival hyperaemia (31%). Other adverse reactions, occurring in 5% to 25% of eyes included: corneal opacity (haze), photophobia, punctate keratitis, eye pain, eye irritation, increased lacrimation, corneal epithelium defect, eyelid oedema, corneal striae, visual acuity reduced, dry eye, and anterior chamber flare.