Amber Ophthalmics, Inc. announced that the first patient has been dosed in the AMB-01-006 (NEXPEDE-1) study assessing the use of Nexagon (lufepirsen ophthalmic gel) for the treatment of persistent corneal epithelial defects (PCED).
Refresh me on the company.
Founded in 2020 and based in San Diego, California, Amber Ophthalmics is a privately-held, clinical-stage biopharmaceutical company developing novel therapeutics to meet unmet ophthalmic medical needs.
Its lead candidate, Nexagon, is being developed as a first-in-class product with a novel mechanism of action for PCED.
Wait, didn’t another company own Nexagon?
Yes, indeed! From a historical perspective, Nexagon was investigated as a drug candidate originally by OcuNexus Therapeutics before the asset was acquired by Eyevance Pharmaceuticals in 2018.
Upon the merger and acquisition of Eyevance by Santen in 2020, Nexagon was carved out of that deal and changed hands again landing at Amber.
Now Nexagon.
Nexagon is an unmodified antisense oligonucleotide that potentially restores ocular homeostasis via downregulating pathogenetically-elevated connexin43 (Cx43) protein transcription (typically associated with direct cell-to-cell communication via gap junctions) and preventing unregulated inflammation linked to PCED.
To note, Nexagon has also received orphan drug designation (ODD) from the FDA.
How is it administered?
The topical medication is designed to be administered by an eyecare professional (ECP) in a clinical setting across fewer sessions than other current standard treatments (which typically include multiple daily patient-administered drops).
Talk about this study.
The randomized, multicenter, double-masked, vehicle-controlled phase 2/3 NEXPEDE-1 study (NCT05966493) is assessing two concentrations of Nexagon (low and high dose) in an estimated 120 patients (ages 2+) diagnosed with PCED.
Patient criteria?
Per Clinical Trials, participants must have:
- No clinical evidence of PCED improvement with 2 weeks before study start
- PCED measuring at least 2 mm along the largest diameter
See the full inclusion and exclusion criteria here.
Now the dosings.
Patients will be divided into three groups and adhere to the following dosing schedule:
- Group 1 (Nexagon high dose [Nex-HD])
- Applied topically weekly for 4 to 8 weeks
- Group 2 (Nexagon low dose [Nex-LD])
- Applied topically weekly for 4 to 8 weeks
- Group 3 (placebo)
- Applied topically weekly for 4 to 8 weeks
What’s being measured?
The primary outcome, measured at the end of the study is the proportion of participants who achieve corneal re-epithelialization (corneal healing) and maintain for a minimum of 28 days, as assessed by corneal fluorescein staining images of PCED via a Central Reading Center.
Secondary outcomes include corneal healing in varying measures as well as an ocular pain assessment survey and visual acuity assessment.
See here for the complete list.
What if patients don’t re-epithelialize?
If they don’t achieve corneal healing within the first 4 weeks of treatment, patients will continue to receive weekly administrations until either they heal or complete 8 weeks of therapy, according to the company.
Gotcha. Is this the first clinical trial on Nexagon?
Actually, no!
In January 2023, Amber released positive topline data from the randomized, prospective double-masked, vehicle-controlled phase 2 NEX-PED-005 (EXPEDE) trial (NCT04081103) on Nexagon that assessed its use for PCED resulting from severe ocular chemical and/or thermal injury (CTI).
Of the participants who received Nexagon—three times over 28 days—67% achieved complete corneal epithelial recovery (compared to 27% who received a placebo).
See here for the coverage.
So when can we expect data from this NEXPEDE-1 study?
Per Clinical Trials, the study is slated to complete by April 2024. Stay tuned for interim data in the meantime!
And the significance?
With no FDA-approved therapy for PCED, Nexagon has the potential to launch a paradigm shift as the first on the market.