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GEOGRAPHIC ATROPHY (GA)

Pre-clinical studies are supporting the development of long-acting PAS-nomacopan for treatment of patients with geographic atrophy (GA) in dry age-related macular degeneration (dAMD)

Geographic atrophy (GA) manifests as a chronic progressive degeneration of the macula, which occurs during late-stage dry age-related macular degeneration (dAMD) and can lead to irreversible vision loss. Approximately 5 million people worldwide are affected,1,2 with nearly 1 million in the U.S.3

There currently are no approved treatment options.

Long-Acting PAS-Nomacopan Development Focused on Four Key Needs in GA

  1. Efficacy
    • Efficacy of complement inhibition in slowing progression of geographic atrophy lesions is well understood
  2. Compliance
    • Long-acting PAS-nomacopan may have the potential to provide extended dose intervals (3-6 months) and less frequent needle injections into the back of the eye, a source of fear, discomfort, and disruption for patients4
  3. Safety
    • LTB4 inhibition has been shown to address a key driver of sight-threatening choroidal neovascularization (CNV), a safety risk associated with certain complement-only inhibitors
  4. Comfort
    • A longer half-life of PAS-nomacopan may allow a lower dose volume with little impact on intraocular pressure (IOP) that can be damaging at high levels over time

Rationale for Bispecific (C5+LTB4) Long-Acting PAS-Nomacopan in GA

Complement inhibitors have been shown in multiple clinical studies to be effective at slowing the progression of GA lesions.5,6 Pre-clinical studies support the potential of long-acting PASylated® nomacopan in GA and its advancement toward IND/IMPD for clinical trials.

  • Half-life of intravitreally (IVT) injected PAS-nomacopan may enable dosing intervals of 3-6 months (other therapies in clinical trials have been dosed monthly or every other month)5,6
  • Half-life may also support a dose volume with little impact on intraocular pressure, which at high levels over time can be damaging7
  • Pre-clinical data show LTB4 inhibition by PAS-nomacopan may also reduce risk of sight-threatening choroidal neovascularization (CNV), a safety risk associated with certain complement-only inhibitors5,6,8,9

References

  1. Wong WL, et al. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health. 2014;2(2):e106-e116.
  2. Rudnicka AR, et al. Age and gender variations in age-related macular degeneration prevalence in populations of European ancestry: a meta-analysis. Ophthalmology. 2012;119(3):571-580.
  3. Friedman DS, et al. Prevalence of age-related macular degeneration in the United States [published correction appears in Arch Ophthalmol. 2011 Sep;129(9):1188]. Arch Ophthalmol. 2004;122(4):564-572.
  4. McClard CK, et al. Questionnaire to Assess Life Impact of Treatment by Intravitreal Injections (QUALITII): Development of a patient-reported measure to assess treatment burden of repeat intravitreal injections. BMJ Open Ophthalmol. 2021;6(1):e000669.
  5. Liao DS, et al. Complement C3 Inhibitor Pegcetacoplan for Geographic Atrophy Secondary to Age-Related Macular Degeneration: A Randomized Phase 2 Trial. Ophthalmology. 2020
  6. Jaffe GJ, et al. C5 Inhibitor Avacincaptad Pegol for Geographic Atrophy Due to Age-Related Macular Degeneration: A Randomized Pivotal Phase 2/3 Trial. Ophthalmology. 2021;128(4):576-586.
  7. Medeiros FA, Alencar LM, Zangwill LM, Sample PA, Weinreb RN. The Relationship between intraocular pressure and progressive retinal nerve fiber layer loss in glaucoma. Ophthalmology. 2009;116(6):1125-33.e333.
  8. Sasaki F, et al. Leukotriene B4 promotes neovascularization and macrophage recruitment in murine wet-type AMD models. JCI Insight. 2018;3(18):e96902. Published 2018 Sep 20.
  9. Eskandarpour et al. Immune-Mediated Retinal Vasculitis in Posterior Uveitis and Experimental Models: The Leukotriene (LT)B4-VEGF Axis. Cells. 2021;10(2):396. Published 2021 Feb 15.