Glaukos Corporation announced the submission of its new drug application (NDA) for Epioxa (Epi-on), a next-generation corneal crosslinking (CXL) iLink therapy, to the FDA.
This news follows just over two months after the company reported positive topline data from a second phase 3 trial evaluating Epioxa for keratoconus.
First thing’s first: an Epioxa refresh.
To understand Epioxa, you’ll need some background on Glaukos’s corneal CXL iLink therapy—originally approved by the FDA in 2016 as the first and only corneal CXL procedure for slowing or stopping keratoconus progression.
What it does: As a minimally-invasive outpatient procedure, the iLink procedure uses a single-use formulation that combines Vitamin B2 (riboflavin) eye drops and ultraviolet (UV) light to stiffen and strengthen corneas weakened by either keratoconus or refractive surgery.
- See here for details on where this UV light originates from (hint: It involves the company’s KXL system).
Back to Epioxa, please.
This second-gen corneal CXL therapy is an epi-on procedure that uses a proprietary novel drug formulation designed to not only reduce treatment time and complexity but also improve comfort and recovery time for keratoconus patients.
Important to note: Epioxa was preceded by Glaukos’s first-gen iLink therapy called Photorexa (Epi-off)—currently the only FDA-approved treatment for progressive keratoconus and corneal ectasia post-refractive surgery.
What’s the difference between the two?
For one: Epioxa uses riboflavin modified to bolster penetration through the epithelium, deliver pulsed UV-A irradiation at increased intensity, and provide supplemental oxygen using “boost” goggles.
- On the other end: Photorexa is a topical agent of riboflavin 5′-phosphate ophthalmic solution) 0.146% that uses photo-activation to create bonds between corneal collagen fibers.
Plus: Photorexa’s epi-off technique refers to a procedure where the outer layer of the cornea (epithelium) is removed prior to treatment, while Epioxa’s epi-on indicates the epithelium is left alone during the procedure.
See here for clinical research on both techniques—where investigators concluded that, while each is effective for slowing keratoconus, Epioxa’s method is preferable.
And from other keratoconus treatments?
Such standard forms of treatment like eyeglasses and specialized contact lenses are known to address the symptoms of keratoconus—not potential halting of the disease.
- See here for other therapies currently in practice, including intraocular lens (IOL) options and photorefractive keratectomy.
Comparatively: Glaukos’s first and second-gen iLink therapies target both slowing and potential mitigation of disease progression.
Interesting … now talk about the supporting phase 3 data you mentioned earlier.
That promising data reported from the second phase 3 confirmatory pivotal trial on Epioxa (as well as the first phase 3 trial … which we’ll get to later) was a key component of this NDA submission.
The highlights version:
- The study was a multi-center, randomized, placebo and sham procedure-controlled phase 3 confirmatory pivotal trial (NCT05759559).
- A total of 312 eyes were enrolled and randomized (study eye only) in a 2:1 ratio to receive Epioxa or a placebo/sham treatment.
- Its purpose was to reduce progression of and/or reduce the maximum corneal curvature (Kmax) in the keratoconus eyes, with primary endpoint measured as mean change in Kmax from baseline to Month 12.
Take note: A special protocol assessment (SPA) was implemented that determined the study to be a success if the difference between both treatment and control arms (in the primary efficacy endpoint) was statistically significant, with a difference of ≥ 1.0 D.
And the findings?
Overall: The study met its pre-specified primary efficacy endpoint by demonstrating a “clinically relevant and statistically significant improvement” in Kmax at 12 months from baseline between both arms.
As for Epioxa’s tolerance:
- 91.5% of enrolled Epioxa-treated participants completed the study
- 90.9% of controlled-treated participants completed the study
Check out the largely-mild adverse events reported among patients.
So … how did Epioxa perform in the first phase 3 trial?
Pretty similar (and just as promising) to the second trial—see here and here for more details.
The only major difference: This first study’s primary efficacy endpoint was measured from baseline to Month 16 (instead of Month 12, as in the second trial).
Nice! Let’s talk overarching significance.
As Glaukos Chairman and CEO Thomas Burns noted, this NDA submission is the next step in the company’s intent to provide keratoconus patients with “the first FDA-approved, non-invasive corneal (CXL) drug therapy that does not require removal of the corneal epithelium.”
How exciting! So what’s next?
Per the FDA’s Prescription Drug User Fee Act (PDUFA) guidelines on NDA submissions, the agency must acknowledge its acceptance of the NDA within 30 or 60 days—and complete its submission within 6 to 10 months.
Timeline-wise: This could translate to a potential H2 (second half of) 2025 NDA acceptance (or the first half of 2026).