Cenegermin

Summary

Cenegermin (Oxervate) is a prescription ophthalmic solution containing recombinant human nerve growth factor (rhNGF). It is approved for the treatment of neurotrophic keratopathy, a condition in which loss of corneal sensory nerve function leads to persistent epithelial defects and stromal ulceration. Clinical studies show that topical cenegermin can accelerate corneal healing and improve ocular surface health in both adult and pediatric patients with this rare, sight‑threatening disease.

Mechanism of Action

Cenegermin supplies exogenous human nerve growth factor to the ocular surface. By restoring NGF levels, it supports the survival and regeneration of corneal sensory nerves, which in turn provide trophic support to the overlying epithelium. This neuro‑trophic signaling promotes epithelial cell migration, proliferation, and wound closure, addressing the underlying nerve deficit that drives neurotrophic keratopathy.

What the Research Shows

A multicenter, double‑masked, vehicle‑controlled pivotal trial (48 patients) demonstrated that eight weeks of cenegermin 20 µg/mL eye drops, administered six times daily, resulted in corneal healing in 69.6% of treated eyes versus 29.2% with vehicle (P = 0.006). Healing was evident as early as four weeks, with reductions in lesion size and disease progression. The treatment was well tolerated, with only mild, transient local adverse events. Review articles describe neurotrophic keratopathy as a nerve‑driven epithelial disorder and highlight cenegermin as a disease‑specific therapy targeting the underlying deficit. A 2025 systematic review of pediatric cases (26 eyes) reported a 76.9% improvement rate, including complete resolution in 73% of eyes, though data were limited to case reports and series. Additional reviews list cenegermin among emerging options for non‑infectious corneal injury, underscoring its role in neurotrophic disease contexts.

Reported Benefits

Evidence from the randomized trial shows cenegermin markedly increases the proportion of eyes achieving corneal re‑epithelialisation compared with vehicle, shortens healing time, and reduces lesion progression. Pediatric case series suggest similar efficacy, with most eyes attaining complete resolution. The drug’s mechanism directly addresses nerve loss, offering a disease‑modifying approach rather than symptomatic relief. Across studies, adverse events were mild, local, and transient, supporting a favorable safety profile for short‑term use.

Limitations of the Evidence

The primary efficacy data derive from a single pivotal trial with a modest sample size; long‑term durability beyond the 24‑week follow‑up is not established. Pediatric evidence consists of uncontrolled case reports and series, lacking randomized comparison. Cost, availability, and the need for frequent dosing may limit real‑world adherence. Cenegermin is indicated only for neurotrophic keratopathy, and its benefit for other corneal injuries remains speculative pending further research.

Safety Considerations

In the pivotal trial, adverse effects were limited to mild, transient ocular irritation, such as redness or discomfort, with no serious systemic events reported. The formulation is a sterile ophthalmic solution; hypersensitivity to any component warrants discontinuation. Because data beyond eight weeks are limited, clinicians should monitor for delayed ocular inflammation or infection, especially in eyes with compromised barriers. No systemic toxicity has been observed, but routine ocular examinations are advisable during treatment.

How It Is Administered

Cenegermin is supplied as a sterile ophthalmic solution (20 µg/mL). In clinical studies, patients instilled one drop into the affected eye six times daily for eight weeks. The medication is stored according to manufacturer guidelines and protected from light. Administration is topical; no systemic dosing is involved.

Routes of Administration

Goals & Uses

• Neurotrophic keratitisOphthalmologyHigh
• Healing of neurotrophic keratitis corneal ulcers/epithelial defectsTherapeuticHigh
• Restoration of corneal sensitivityTherapeuticModerate
• Corneal nerve regenerationTherapeuticModerate
• Prevention of disease progression to corneal perforationTherapeuticModerate

Contraindications

• Active ocular or periocular infection not adequately treatedInfectiousModerate
• Hypersensitivity to cenegermin or any excipientAllergic/ImmunologicHigh

Adverse Effects

• Increased intraocular pressureOcularRare
• Increased lacrimationOcularCommon
• Foreign body sensationOcularCommon
• Conjunctival hyperemiaOcularCommon
• Ocular painOcularCommon
• Ocular hyperemia (conjunctival redness)OcularCommon
• Corneal depositsOcularCommon
• Ocular inflammationOcularUncommon
• Eye painOcularCommon

Drug Interactions

• Benzalkonium chloride-containing eye dropsModerate
• Other ophthalmic solutionsLow
• Other ophthalmic medicationsLow

Population Constraints

• Pediatric patients (under 18 years)AgeRelative
• Pediatric patients (<1 year)AgeRelative
• Contact lens wearersDevice InteractionRelative
• Pregnant or breastfeeding womenReproductiveRelative

Regulatory Status

• European UnionApprovedApproved: Neurotrophic keratitisMarketed as Oxervate.
• United StatesInvestigationalUnder FDA review; not yet approved.
• United KingdomApprovedApproved: Neurotrophic keratitisFollows EMA approval.

Approved by the EMA in 2017 and the FDA in 2018 for moderate to severe neurotrophic keratitis. Designated as an orphan drug in both the EU and US given the rarity of the condition.

Evidence & Sources

• Topical Recombinant Human Nerve Growth Factor (Cenegermin) for Neurotrophic Keratopathy: A Multicenter Randomized Vehicle-Controlled Pivotal Trial
  Journal ArticleModeratePflugfelder SC, et al.2020-01-01T00:00:00.000000Z
• Neurotrophic keratopathy
  Journal ArticleModerateDua HS, et al.2018-01-01T00:00:00.000000Z
• Treatment of Non-Infectious Corneal Injury: Review of Diagnostic Agents, Therapeutic Medications, and Future Targets
  Journal ArticleModerateDang DH, Riaz KM, Karamichos D2022-01-01T00:00:00.000000Z
• Topical Cenegermin for Pediatric Neurotrophic Keratopathy: A Review of the Literature and Systematic Review
  Journal ArticleHighBakr M, et al.2025-01-01T00:00:00.000000Z
• Quintessence of currently approved and upcoming treatments for dry eye disease
  Journal ArticleModeratePatil S, et al.2025-01-01T00:00:00.000000Z

Frequently Asked Questions