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Retinal Physician

Article | 2025 Retina World Congress

Fas Inhibition Shows Neuroprotective Benefit for GA

In a phase 1b study, eyes treated with ONL1204 demonstrated reductions in geographic atrophy lesion growth.

By: Jim Gallagher, senior managing editor
Retinal Physician May 9, 2025

Clinical Scorecard: Fas Inhibition Shows Neuroprotective Benefit for Geographic Atrophy

At a Glance

CategoryDetail
ConditionGeographic Atrophy (GA) secondary to Age-related Macular Degeneration (AMD)
Key MechanismsInhibition of Fas receptor activation to prevent photoreceptor apoptosis and retinal inflammation
Target PopulationPatients with GA secondary to AMD
Care SettingOphthalmology clinics with intravitreal injection capability

Key Highlights

  • ONL1204, a Fas inhibitor peptide, reduced GA lesion growth by up to 50% after two injections over 6 months.
  • The treatment was well tolerated with minimal adverse events and no intraocular inflammation or choroidal neovascularization.
  • Exploratory AI analyses showed structural retinal improvements correlating with functional benefits.

Guideline-Based Recommendations

Diagnosis

  • Diagnosis of GA secondary to AMD using clinical examination and imaging including OCT.

Management

  • Consider intravitreal ONL1204 injections as a neuroprotective treatment to reduce GA lesion growth.
  • Dosing regimens studied include single injection or two injections spaced 3 months apart.

Monitoring & Follow-up

  • Monitor lesion growth via imaging (e.g., OCT) and assess best-corrected visual acuity (BCVA) and low-luminance BCVA.
  • Observe for treatment-emergent adverse events including intraocular pressure changes and vitreous floaters.

Risks

  • Potential transient increase in intraocular pressure and mild vitreous floaters, primarily at higher doses.
  • No observed cases of choroidal neovascularization or intraocular inflammation in phase 1b study.

Patient & Prescribing Data

Patients with GA secondary to AMD enrolled in phase 1b clinical trial

Single or two intravitreal injections of ONL1204 demonstrated significant reduction in GA lesion growth with good safety and tolerability.

Clinical Best Practices

  • Use imaging biomarkers such as ellipsoid zone attenuation and retinal pigment epithelium area at risk to assess treatment response.
  • Employ AI tools to complement structural and functional evaluation of retinal changes.
  • Consider dose escalation to optimize lesion growth reduction while monitoring safety.

References