6 · Emerging therapies — cellular, gene & innovative
Connexin 43 modulation — Nexagon (lufepirsen) & aCT1 peptide (Granexin)
Review — modulators of corneal healing › 6 · Emerging therapies — cellular, gene & innovative › Connexin 43 modulation — Nexagon (lufepirsen) & aCT1 peptide (Granexin)
Connexin 43 modulation — Nexagon (lufepirsen) & aCT1 peptide (Granexin)
Cx43 antisense oligonucleotide (Amber Ophthalmics) · Cx43 C-terminal mimetic peptide (Xequel Bio) · the most advanced innovative candidate
Oxford II (Nexagon) · V (corneal aCT1)
Moderate (Nexagon)
Future · pivotal trial ongoing
Mechanism of actionInjury upregulates Cx43 at the wound edge → ATP release via hemichannels, inflammation, impaired epithelial migration. Nexagon (antisense) transiently reduces Cx43 translation → ↓inflammation, ↑re-epithelialisation. aCT1/Granexin (peptide) binds the C-terminal tail of Cx43 (and ZO-1) → junctional remodelling, ↓inflammation.
IndicationsNon-infectious PED (incl. post severe chemical/thermal burn — Nexagon); impaired diabetic wound healing (peptide, preclinical). ~100,000 PED patients/year in the USA, with no approved treatment.
Route & dosageNexagon: topical ophthalmic gel, low in-office application frequency ("as few as 5" applications, weekly up to week 8 if needed). aCT1: topical (preclinical in the cornea).
Level of evidenceNexagon: Oxford II (positive phase 2) · Scale: Moderate (investigational). Pivotal trial NEXPEDE-1 (phase 2/3, NCT05966493) ongoing. Corneal aCT1: Oxford V / Investigational.
| FDA | Nexagon & Granexin: investigational (no approval). Nexagon in phase 2/3. |
|---|---|
| EU MA / France / Asia | Not approved; trials (programme conducted in the USA). |
Key studies: NEXPEDE-1 (NCT05966493) ; Grupcheva et al., Invest Ophthalmol Vis Sci 2012 (Cx43 antisense) — PMID 22247467 ; controlled-release Cx43 peptide, diabetic cornea (PLoS One 2014) — PMID 24466155.