Glaukos Corporation has received U.S. regulatory approval from the FDA for Epioxa HD (riboflavin 5’-phosphate ophthalmic solution) / Epioxa (riboflavin 5’-phosphate ophthalmic solution) 0.177%, a corneal collagen crosslinking (CXL) iLink therapy.
The long-anticipated announcement is right on schedule after the company’s February 2025 new drug application (NDA) submission.
How exciting! Start with the basics of this.
Epioxa (pronounced E pee ox’ ah) is the latest iteration of Glaukos’s corneal CXL therapy Photrexa (epithelium [epi]-off), a minimally-invasive outpatient procedure that was first FDA-approved in 2016.
From an industry standpoint: iLink was the first and only corneal CXL procedure commercially available in the United States for slowing or halting keratoconus progression.
- See here for how it does this (and click here for four key examples of why using an FDA-approved CXL procedure is so critical).
For greater context: Check out how iLink compares to standard forms of keratoconus treatment.
Next up: Give us the rundown on Epioxa.
What to know about it: The novel, oxygen-enriched topical therapeutic is bioactivated by ultraviolet (UV) light designed as an incision-free alternative to traditional CXL procedures.
Its indication: For use in epi-on corneal collagen CXL for the treatment of keratoconus in adults and pediatric patients aged 13 years and older
But more specifically …
This epi-on (note the difference from Photrexa) utilizes a proprietary novel drug formulation to reduce treatment time and complexity as well as shorten recovery time.
- And as a bonus for patients: It’s intended to eliminate pain typically associated with the epithelium's removal.
What’s the recommended dosage?
Importantly, Epioxa HD and Epioxa are supplied in single-dose syringes (discarded after use) intended for topical ophthalmic use.
Got it. Circle back and talk about that novel formulation.
The formulation is actually a two-in-one composed of Epioxa and Epioxa HD.
And take note: Epioxa uses riboflavin modified to:
- Bolster penetration through the epithelium
- Deliver pulsed UV-A irradiation at increased intensity
- Provide supplemental oxygen (O2n) via “boost goggles”
In other words: Epioxa and Epioxa HD are sequentially administered during the CXL procedure and followed by UV activation in an oxygen-enriched environment, according to Glaukos.
Any contradictions to be aware of?
A few … both Epioxa and Epioxa HD are contraindicated in:
- Patients with known hypersensitivity to benzalkonium chloride (or any ingredients in either therapeutics)
- Aphakic and pseudophakic patients without a UV-blocking intraocular lens
As for potential warnings and precautions: Caution is advised for patients with a history of herpetic keratitis due to the potential for reactivation of herpes keratitis.
And along these lines … how about potential adverse reactions?
There’s definitely a few to be aware of, based on clinical data (which we’ll discuss later).
The following occurred in 5% to 25% of patients during clinical trials:
- Corneal opacity (haze), photophobia, punctate keratitis, eye pain, eye irritation, increased lacrimation, corneal epithelium defect, eyelid oedema, corneal striae, reduced visual acuity, dry eye, and anterior chamber flare.
Now to that supporting clinical data.
We’ve got two prospective, randomized, multicenter, double-masked phase 3 trials to discuss—or rather, the findings from both—that were included in Epioxa’s NDA submission.
These include positive data from a first (NCT03442751) and second study (NCT05759559; a confirmatory pivotal trial) that evaluated Epioxa among 400+ patients’ keratoconus eyes.
Give me specifics.
Both studies met their primary endpoints and demonstrated Epioxa's favorable safety profile.
For example: In the second study—which aimed to reduce the progression of and / or reduce the maximum corneal curvature (Kmax) in keratoconus eyes—Epioxa resulted in a “clinically relevant and statistically significant improvement” in Kmax at Month 12 (from baseline).
- 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.
Let’s talk big-picture.
The significance of Epioxa’s approval is far reaching.
Glaukos Chairman and CEO Thomas Burns noted that the second-gen iLink therapy represents a new standard-of-care for keratoconus patients as “the first FDA-approved topical drug therapy that does not require removal of the corneal epithelium.
How about from a clinical professional's perspective?
We’ll start with feedback from Eric D. Donnenfeld, MD.
His credentials:
- In private practice at Ophthalmic Consultants of Long Island in Rockville Center, New York
- Trustee of Dartmouth Medical School
- Clinical professor of ophthalmology at New York University (NYU)
- Past-president of the American Society of Cataract and Refractive Surgeons (ASCRS)
Dr. Donnenfeld noted the significant unmet need for a better treatment for young keratoconus patients as well as the drawbacks associated with epi-off CXL procedures: significant pain, a long recovery time, and complications.
- These often dissuade keratoconus patients from going through with the procedure, he said.
And with Epioxa?
"An oxygen-enriched environment (such as the one provided by Epioxa) is critical to the success of CXL and is the key to Glaukos gaining approval for a treatment that does not require removal of the epithelium or skin of the eye,” Dr. Donnefeld said.
- “As corneal surgeons, we have an obligation to our patients to preserve vision, improve quality of life and to avoid corneal transplantation in these young patients,” Dr. Donnenfeld said. “The introduction of Epioxa is an important step forward towards this important goal."
How about from the OD side?
Mitch Ibach, OD, a cornea, glaucoma, cataract, and refractive surgery specialist at Vance Thompson Vision in Sioux Falls, South Dakota, noted that his practice participated in the investigational clinical trials that led to Epioxa’s regulatory clearance.
He shared that patients’ experience during the epi-on trials was “a significant improvement” from those who undergo epi-off CXL.
- “Patients will always choose a procedure with less induced pain and a quicker visual recovery,” Dr. Ibach said, and in my experience leaving the epithelium in place shows those benefits.”
What are his thoughts on ODs’ role in keratoconus treatment?
Dr. Ibach noted that, given a large percentage of keratoconus starts in optometric practices, “optometrists will continue to play a critical role in detecting keratoconus and collaboratively managing care for these patients.”
- “The continued goal should be treating keratoconus patients earlier in the disease process where more of the visual potential is maintained,” he emphasized.
He concluded: “The eyecare ecosystem works most efficiently when everyone is working side by side. Collaboratively, if the guiding light is treating more patients earlier in the disease, patients win."
Speaking of earlier treatment, is Glaukos planning any supporting initiatives?
Indeed. To coincide with Epioxa’s upcoming launch (which we’ll get to in a moment), the company will also launch key initiatives to promote patient awareness and treatment access—as well as addressing long-standing challenges of both underdiagnosed and under-treated keratoconus patients.
- Streamlined patient access support programs
- Launch of a co-pay assistance program (to reduce financial barriers)
- Integration of healthcare provider and patient-focused strategies
- To improve education and engagement
- Launch of broad disease awareness and detection programs
- To encourage earlier and more widespread screenings for/diagnosis of keratoconus
Alrighty, now the big question: When will Epioxa be commercially available?
Fairly soon—Q1 2026.