Glaukos Corporation announced the FDA has accepted its new drug application (NDA) for Epioxa (Epi-on), a second-generation corneal crosslinking (CXL) iLink therapy.
To note: This follows the company’s late-December 2024 submission to the federal agency.
Let’s start with this iLink therapy.
Epoxia is based on Glaukos’s minimally-invasive outpatient procedure: the corneal CXL iLink therapy.
About iLink: FDA-approved in 2016, this was the first (and is still the only) corneal CXL procedure commercially available in the United States for slowing or halting keratoconus progression.
- The first-gen iLink therapy is dubbed Photorexa (Epi-off).
How does it do this, exactly?
Via a single-use formulation of the following components to stiffen and strengthen corneas weakened by keratoconus or (corneal ectasia post-)refractive surgery:
- Vitamin B2 (riboflavin) ophthalmic solution
- Ultraviolet (UV) light (details about this here)
Now to Epioxa.
What it is: The latest iteration of the iLink therapy designed as an epi-on procedure.
What it involves: The use of a proprietary novel drug formulation that reduces treatment time and complexity as well as improves keratoconus patients’ recovery time and overall comfort.
- See here for a rundown of the difference between these epi-on and epi-off procedures.
- And click here for how these iLink therapies compare to other keratoconus treatments (a major distinction: treating symptoms versus slowing or mitigating disease progression).
And about this NDA acceptance ...
To be extremely technical and specific here: Glaukos noted that it had received “Day 74” notification from the FDA that acknowledged its NDA submission was “sufficiently complete to permit a substantive review.”
In other words: NDA acceptance was granted.
Got it. So what clinical data is this NDA acceptance based on?
Phase 3 data from two clinical trials evaluating Epioxa among keratoconus eyes—with the second of the two (a confirmatory pivotal study) playing a key role in the application’s submission.
Those studies:
- First phase 3 trial: NCT03442751
- Second phase 3 trial: NCT05759559
- Note: The details of this study on Clinical Trials have been redacted
- See here for an overview of it.
- Note: The details of this study on Clinical Trials have been redacted
And the data to focus on here?
We’ll zero in on the most recently reported findings: positive topline data from the second phase 3 study released in October 2024.
The target for this study: To reduce the progression of and / or reduce the maximum corneal curvature (Kmax) in keratoconus eyes.
The primary endpoint: A difference of ≥ 1 diopter (D) between treatment and control arms with a mean change in Kmax from baseline to Month 12.
- Why focus on Kmax: This is an objective measurement that the FDA has deemed to be acceptable as a primary efficacy outcome for keratoconus pivotal trials.
Also take note: The primary endpoint for that other phase 3 trial was the same, save for its duration extending to only 6 months.
Numbers, please.
In meeting its primary endpoint and demonstrating a “clinically relevant and statistically significant improvement” in Kmax at Month 12 (from baseline), the study found:
- 91.5% of Epioxa-treated patients completed the study
- 90.9% of controlled-treated patients complete the study
See the similar positive data from that first phase 3 trial (which demonstrated a Kmax treatment effectiveness of -1.0 D (p = 0.0004) at 6 months).
Any notable adverse events between the two studies?
Epioxa was reported to be generally well-tolerated, with the majority of adverse events (AEs) referred to as “mild and transient in nature.”
See here for a rundown of the most common AEs observed in the first phase 3 trial.
Let’s talk overarching significance of this therapy.
If all goes according to plan, Epioxa would become the first non-invasive corneal CXL therapy with no need for corneal epithelium removal to reduce keratoconus progression.
How exciting! So when might this happen?
Per the FDA’s standard process, the agency has 10 months to review the complete Epioxa NDA submission.
A Prescription Drug User Fee Act (PDUFA) date of Oct. 20, 2025 has been set.