CXL Ophthalmics Announces Results of Successful Phase 2 Clinical Trial in Epi-On Cross-linking for Keratoconus
Largest cross-linking study to date summarized at The American Academy of Ophthalmology Conference, topline results to be available in NIH clinical trial registry.
Encinitas, CA, November 14, 2021 – CXL Ophthalmics, LLC, a clinical-stage company developing treatments for corneal ectasia, today released topline results of its landmark Phase 2 Trial in transepithelial (Epi-On) cross-linking. Results were summarized as part of the “Hot Topics 2021” session at the AAO Conference in New Orleans, LA by Dr. Roy Rubinfeld, Chief Scientific Officer. Simultaneously, results were released to the NIH clinical trials registry, ClinicalTrials.gov, for study CXL-005 (NCT03029104). These will be available after NIH Protocol Registration and Results System review.
The CXL-005 study, “Collagen Cross-Linking with Ultraviolet-A in Asymmetric Corneas,” enrolled 2,258 participants with a diagnosed corneal ectasia. Epi-on cross-linking was performed with CXLO’s novel EpiSmart™ system. The purpose of the study was to demonstrate safety, efficacy, and to establish the optimal UVA dose. Three cohorts were treated with varying doses of UVA: Group 1 – 4mW/cm2 for 20 minutes; Group 2 – 6mW/cm2 for 20 minutes, and Group 3 – 4mW/cm2 for 30 minutes. Patients were monitored at baseline pre-procedure, and at 3-, 6-, and 12-months post-procedure. The 6-month follow-up was required, and 12 month was optional but encouraged. The primary endpoint was change from baseline in Corrected Distance Visual Acuity (CDVA). Secondary endpoints were change from baseline in uncorrected Distance Visual Acuity (UDVA) and in maximum keratometry (KMax). Safety parameters and adverse events were monitored at all time points.
2,228 subjects were treated: Safety analysis was reported in all these subjects. 86% of subjects had a diagnosis of keratoconus, qualifying for the prospective efficacy analysis set.
One eye per patient was the unit of analysis, but 71% of patients elected simultaneous bilateral treatment.
Subjects averaged 32 years of age and ranged from 8-79. Average baseline vision was about 20/40 corrected and 20/130 uncorrected. Average KMax (± SD) was 59 ± 10 Diopters.
There was not a substantial or significant difference between the treatment groups, so Group 1 (4mW/cm2 for 20 minutes) was selected as optimal based on lowest dose.
Of 1,605 keratoconus subjects with complete baseline assessments. Of these, 1,400 completed the 6-month outcome primary efficacy assessments. 784 subjects were then assessed at 12 months.
The overall mean change in CDVA was -0.063 and -0.068 logMAR at 6- and 12-months, respectively (p << 0.0001 for improvement in each of three groups). The Group 1 CDVA change from baseline to 12 months was -0.074 ± 0.012 logMAR (mean ± SE, p<<0.0001), nearly a line of vision improvement.
Overall, 81% of keratoconus patients maintained or improved their vision, with 14% gaining 3 lines or more of CDVA. There was a positive trend in younger patients. In patients 21 years old or younger in Group 1, 89% of subjects had stable or improved vision, with 25% gaining 3 or more lines of CDVA.
Overall, UDVA was significantly improved by one line of vision at 6- and 12-months (p << 0.001 for improvement at both timepoints and for each group).
Overall, KMax was significantly flattened by -0.45 ± 0.09 D at 12 months (p << 0.001).
The safety profile was benign and consistent with non-invasive treatment. 8.7% of patients reported any treatment-emergent adverse event: most were mild and transient. The events reported in the largest proportion of subjects were mild corneal epithelial defects (1.4%), Meibomian gland dysfunction (0.7%), punctate keratitis (0.5%), and dry eye (0.4%). There were no serious adverse events related to the treatment.
“We were pleased to find substantial and significantly better vision for keratoconus patients post-treatment, which continued to improve over 12 months. The rate of adverse events is the lowest ever reported for a cross-linking treatment studied on anything near this scale,” said Dr. Rubinfeld. “Most patients were back to work or school in a day or two. This study demonstrated that a non-invasive, bilateral treatment that preserves vision is possible. We hope that in the future no keratoconus patient has to wait for permanent vision loss before being treated.”
Mike Webb, CXLO’s chief executive officer, added, “CXL-005 was the largest study of cross-linking to date using any technology. It tested a non-invasive cross-linking system that would be a vast improvement in safety and patient comfort, and the data are consistent with that idea. Based on our success here, we have planned placebo-controlled phase 3 studies to show definitively that our epi-on treatment improves vision for keratoconus patients. FDA has reviewed our protocols, and we’re excited to begin work to bring this treatment to patients.”
About EpiSmart, Cross-linking and Keratoconus
The patented EpiSmart system, including Ribostat, is designed to optimize cross-linking therapy for keratoconus, allowing non-invasive treatment via simultaneous bilateral application of UV light without the need for surgical removal of the corneal epithelium. The safety and efficacy of EpiSmart was investigated in a recently concluded 2,258-subject phase 2 trial, and CXL Ophthalmics is preparing to initiate phase 3 clinical trials for the treatment of keratoconus with EpiSmart.
Corneal collagen cross-linking is a process used to strengthen corneas affected by keratoconus and halt disease progression. Riboflavin (vitamin B2) and UV-A light interact to cause new bonds to form between proteins, fortifying the structure of weakened corneas. The currently approved treatment approach is called “epi-off cross-linking” and involves a painful recovery, delayed return of vision and significant risk of scarring or infection. CXL Ophthalmics has developed a non-invasive system for “epi-on cross-linking” (without surgical removal or chemical disruption of epithelium) that could allow for earlier, safer, and more convenient treatment, potentially saving vision for millions of patients.
Keratoconus is a bilateral, progressive corneal degenerative disease accompanied by corneal thinning. In later stages, the cornea takes on a bulging, conical shape, leading to irregular astigmatism that is difficult or impossible to correct and results in loss of functional vision. Typical onset of symptoms occurs in the late teens to early twenties but can be manifest in children younger than 10 years old. Based on global epidemiological research, estimates of keratoconus prevalence range from 1:2000 to 1:100. The recent Raine study, performed in Australia, showed a prevalence at 1.2%, which implies a US prevalence of more than 3 million.
About CXL Ophthalmics
CXL Ophthalmics is an ophthalmology-focused medical device and pharmaceutical company dedicated to the discovery, development, and commercialization of innovative treatments for corneal diseases. CXL Ophthalmics’ cross-linking system, EpiSmart, functions by photochemically strengthening the cornea. EpiSmart is not approved for commercial use and is currently in clinical trials supervised under an IND on file with the U.S. Food and Drug Administration (FDA). For more information, please visit www.cxlophthalmics.com.
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CXL Ophthalmics
Edward Parsons, Chief Business Officer
info@cxlophthalmics.com