Glaukos Corporation has released positive topline data from its second phase 3 confirmatory pivotal trial evaluating Epioxa (Epi-on), a next-generation corneal crosslinking (CXL) iLink therapy for the treatment of keratoconus.
Where to begin?
Let’s back up to talk about Glaukos’s corneal CXL iLink therapy.
Approved by the FDA in 2016, the iLink procedure is a minimally-invasive outpatient procedure that 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.
Note: The UV light is taken from Glaukos’s KXL system—a corneal CXL procedure that uses high-power UV to cause riboflavin to fluoresce in the cornea.
- Important to know: It is the first and only FDA-approved corneal CXL procedure that slows or stops keratoconus progression.
Now explain Epioxa.
Epioxa (Epi-on) is a second-generation corneal CXL therapy utilizing a proprietary novel drug formulation (more on that in a moment) that’s designed to reduce treatment time and complexity as well as improve comfort and recovery time for keratoconus patients.
Its predecessor: The first-generation corneal CXL therapy of Photrexa (Epi-off), currently the only FDA-approved treatment for progressive keratoconus and corneal ectasia following refractive surgery.
- Both Epioxa and Photrexa are a form of iLink therapy
How do these therapies differ?
As a topical agent, Photrexa (riboflavin 5′-phosphate ophthalmic solution) 0.146% uses photo-activation to create bonds between corneal collagen fibers.
Comparatively: Epioxa uses riboflavin that has been modified to bolster penetration through the epithelium, deliver pulsed UV-A irradiation at increased intensity, and provide supplemental oxygen using “boost” goggles.
Noted. Now talk about this phase 3 trial.
As the company noted, this was the second phase 3 confirmatory trial on Epioxa (we’ll get to that first trial later).
- The details: This was a multi-center, randomized, placebo and sham procedure-controlled phase 3 confirmatory pivotal trial (NCT05759559) that enrolled 312 eyes.
- The setup: Study eyes were randomized in a 2:1 ratio to receive Epioxa or a placebo/sham procedure control treatment.
- The goal: To either reduce progression of and/or reduce the maximum corneal curvature (Kmax) in the keratoconus eyes.
- The primary efficacy endpoint: Mean change in Kmax from baseline to Month 12.
Note about Kmax: This is a common metric used for assessing the effectiveness of CXL against keratoconus.
- For this study: Kmax—previously accepted by the FDA as a primary efficacy outcome for keratoconus pivotal trials—is referred to as an “objective measurement of the steepest corneal curvature based on corneal topography, where an increasing Kmax denotes corneal steepening and keratoconus disease progression.”
Any SPA agreements to be aware of?
Yes, actually. A special protocol assessment (SPA) was agreed on by both Glaukos and The FDA that determined:
The study would be deemed 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.
Alrighty, now let’s get to these findings.
First: Glaukos reported that the study successfully met its pre-specified primary efficacy endpoint, demonstrating a “clinically relevant and statistically significant improvement” in Kmax at 12 months from baseline between both arms.
- The numbers: A Kmax treatment effect of –1.0 diopter (D) (p <0.0001), determined as prospectively defined least square mean Kmax change from baseline in the Epioxa-treated arm versus the sham/placebo-controlled arm at the Month 12 study endpoint.
Nice! And how was Epioxa tolerated?
Generally speaking, the therapy was “well-tolerated.”
In total:
- 91.5% of enrolled Epioxa-treated participants completed the study
- 90.9% of controlled-treated participants completed the study
Any adverse events?
No Epioxa-treated participants discontinued the study early due to any adverse events (AEs), and no ocular serious AEs were reported.
To note: The majority of reported AEs were “mild and transient in nature,” with no evidence of treatment-related systemic effects observed during the study—as well as no change in corneal endothelial cell counts throughout the 12-month evaluation period.
Sounds promising! And how does this data compare to the previous?
The company’s first phase 3 trial (NCT03442751)—a multicenter, randomized, placebo-controlled pivotal study—evaluated Epioxa in 279 eyes with progressive keratoconus.
Its pre-specified primary efficacy endpoint mirrored that of this second trial—but measured from baseline to Month 6.
Now the findings: The study met its primary efficacy endpoint and was confirmed by the FDA, which gave their stamp of approval for its results to support the submission and review of an eventual new drug application (NDA) for Epioxa.
Interesting … anything else to know?
In addition to this new phase 3 data, Glaukos also reported completing a “successful clinical pre-NDA meeting” with the FDA on Epioxa.
That meeting’s purpose: To receive FDA agreement on “the content of the proposed NDA, and in particular, to confirm that the company’s clinical data package (of two phase 3 trials) would be sufficient to support an NDA submission and review.”
- And the result: The federal agency gave the OK for Glaukos’s proposed clinical data package.
Speaking of that NDA submission … do we have a timeline?
Indeed we do. Right now, the company is anticipating using this combined phase 3 pivotal trial data to support an NDA submission for Epioxa by the end of 2024.
And the potential significance of Epioxa?
If approved by the FDA, the second-gen iLink therapy has the potential to become the first non-invasive corneal CXL therapy that doesn’t require removal of the corneal epithelium.
In other words, it would be a game-changer for the keratoconus community