Glaukos recently announced the publication of results from a phase 3, confirmatory pivotal trial for Epioxa HD / Epioxa (riboflavin 5–phosphate ophthalmic solution 0.239% / 0.177%) for the treatment of keratoconus (KC) in Ophthalmology and Therapy.
Let’s start with a look at this therapy.
Epioxa is the first and only epithelium (epi-on), minimally-invasive corneal crosslinking (CXL) therapy for the treatment of KC.
Its regulatory status:
- Approved by the FDA in October 2025,
- Commercially launched to the U.S. market in March 2026
- Received a permanent J-code in April 2026
Give me the rundown how Epioxa works.
What it is: A novel, oxygen-enriched, ultraviolet (UV)-activated, and non-invasive (epi-on) CXL approach that strengthens the cornea without needing surgery (ie: a traditional CXL procedure).
- The indication: For use in epi-on corneal collagen CXL to treat KC in patients aged 13+
- The recommended dosage: Available as a single-dose syringe administered via topical ophthalmic application
- This applies to both Epioxa and Epioxa HD, as per its prescribing information (which can be viewed here)
Looking for more information? Click here to check out our abbreviated rundown on everything Epioxa-related.
So how did Epioxa perform in previous clinical trials?
Two prospective, randomized, multicenter, double-masked phase 3 trials supported Epioxa’s FDA approval (NCT03442751 and NCT05759559; a confirmatory pivotal trial, respectively), evaluating Epioxa among 400+ keratoconic eyes.
Both studies met their primary endpoints and demonstrated Epioxa's favorable safety profile.
- Check out the high percentage of tolerance among Epioxa-treated patients.
- And for data on that first study (which only measured from baseline to Month 6), see here.
And this new research?
The recently published study analyzed data from the second phase 3 trial (NCT05759559), reporting statistically significant and clinically meaningful improvement in Kmax at Month 12 (-0.5 D improvement in Epioxa-treated eyes vs. +0.4 D worsening in the sham group).
Some details from the study:
- Location: Conducted at 28 U.S. clinical sties
- Cohort: Enrolled patients ranging from 13-51 years old
- Primary outcome measure: 1.0 D difference in Kmax at Month 12
- Key inclusion/exclusion criteria:
- Axial topography consistent with KC and central or inferior steepening on Pentacam and clinical signs of KC (ie., Fleischer ring, Vogt striae, corneal thinning, corneal scarring, and/or scissoring of the retinoscopic reflex) and Kmax ≥47.00 D
- Corneal thickness ≥325 µm
- No prior corneal surgery or other ocular conditions and no history of or risk for delayed epithelial healing
What was the methodology?
Eyes were randomized 2:1 to Epioxa treatment or sham/placebo control, and randomization was stratified by baseline severity (mild vs. moderate/severe) and by age (<30 vs. ≥30 years) within each site.
- Epioxa-treated eyes (n=200) received Epioxa, and underwent UV-A pulsed irradiation (1 second on/1 second off) with supplemental oxygen delivered via Boost Goggles
- Control eyes (n=112) received placebo drops and underwent a sham irradiation procedure
Note: Eyes initially randomized to sham/placebo were crossed over to receive Epioxa treatment after 12 months and followed for an additional 6 months.
Anything else to know about the study?
The difference in Kmax between the two groups (-1.0 D [95% confidence interval (CI): -1.3 to -0.6; p < 0.0001] demonstrated statistical superiority.
Notably: Both eyes of a participant could be enrolled in the Epioxa trial, with the second eye treated as early as 1 week after the first eye.
Ultimately: KC was slowed or halted in treated eyes, while sham/placebo eyes continued to show steepening, with consistent trends across age, sex, race, and baseline severity subgroups, including eyes with mild KC.
Any new safety signals?
Nope. In fact, the safety profile was favorable with no serious ocular adverse events and mild, transient treatment-emergent events.
The procedure’s tolerability and safety were also bolstered by the absence of clinically meaningful changes in:
- Corneal thickness
- Endothelial cell count
- Intraocular pressure
- Macular thickness
Now let's talk big picture: What’s the importance of Epioxa?
The study authors highlighted that “early detection and treatment of KC is vital to reduce the economic burden of the disease by diminishing the need for corneal transplantation.”
Moreover: A 2025 study by Rapuano et al. analyzed the economic impact of CXL treatment in KC management, and found that compared to patients who did not receive CXL, those who did were:
- Less likely to receive penetrating keratoplasty surgery
- Spent fewer years in advanced KC disease stages
- Had fewer medical costs and higher quality-adjusted life years
Take away.
The pivotal phase 3 study of Epioxa met its primary efficacy endpoint, halting or slowing KC progression, while also helping to improve corneal integrity and maintain visual function.
Why this matters: This data supports early intervention in KC management to preserve corneal integrity, suggesting that a “watch and wait” approach carries a real risk of disease progression and subsequent changes in quality of life.
So what’s the plan moving forward?
As KC progression can recur after the 1-year follow-up, the study authors noted that an extension clinical trial has already been initiated to enroll patients who completed the current trial and monitor them for a longer duration of time.