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Depletion of Specific Cell Populations by Complement Depletion
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Compendium of current complement therapeutics.

Wioleta M Zelek1, Long Xie2, B Paul Morgan1

  • 1Systems Immunity Research Institute and Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff, CF14 4XN, UK.

Molecular Immunology
|August 26, 2019
PubMed
Summary
This summary is machine-generated.

The complement system, crucial for immunity, also drives disease. Inhibiting it, as with eculizumab for paroxysmal nocturnal hemoglobinuria, validates complement therapeutics, with new drugs emerging.

Keywords:
Clinical trialComplementDiseaseDrugEculizumabTherapeutic

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Area of Science:

  • Immunology
  • Pharmacology

Background:

  • The complement system is vital for innate immunity and tissue homeostasis.
  • However, it also contributes to disease pathogenesis, exacerbating inflammation.
  • Paroxysmal nocturnal hemoglobinuria (PNH) therapy with eculizumab validated complement inhibition.

Purpose of the Study:

  • To highlight complement therapeutic targets, modalities, and development status.
  • To provide a snapshot of the rapidly evolving complement drug landscape.
  • To illustrate future clinical choices for complement-targeted therapies.

Main Methods:

  • Review of approved and clinically developing complement drugs.
  • Analysis of targets, mechanisms of action, and delivery routes.
  • Assessment of clinical trial progress and attrition rates.

Main Results:

  • Eculizumab's success in PNH spurred significant investment in complement therapeutics.
  • Numerous drugs targeting various complement components are in development, with some in Phase 3 trials.
  • Despite high attrition, valuable lessons have informed next-generation drug design.

Conclusions:

  • Complement inhibition is a validated therapeutic strategy with growing potential.
  • Next-generation drugs aim to overcome previous development hurdles and improve patient access.
  • Future treatment decisions will balance efficacy, cost, target, modality, and delivery.