Complement Pathway Targeting Therapies in C3G: An Overview of Clinical Trials

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Update on Complement Inhibitor Therapies and Clinical Trials in C3G

Jonathan Barratt, MBChB, PhD, FRCP, provided insights into ongoing developments in complement inhibitor therapies, particularly for treating C3G.

• Recently Approved:
  • Iptacopan, an oral small molecule factor B inhibitor, recently received FDA approval and is considered a transformative agent in this space.
• Expected Next Approval:
  • Pegcetacoplan, a C3 inhibitor, is anticipated to be the next medication approved by the FDA.

• Based on promising phase 3 trial data presented at ASN, it shows significant potential for improving patient outcomes.

• Key Comparisons:
  • Iptacopan (oral capsule) vs pegcetacoplan (injection): Different routes of administration may influence clinical decision-making and patient adherence.
• Other Therapeutic Agents in Trials:
  • Anti-C5 receptor inhibitors like avacopan
  • Anti–factor D agents
  • Dual C3/C5 inhibitor
  • These are currently in earlier phases of development and not expected to reach approval imminently.
• Challenges in Clinical Trials:
  • Recruiting for C3G-specific trials remains difficult due to the rarity and strict inclusion criteria of the disease. Even experienced trial centers are facing challenges in enrollment.
• Clinical Relevance:
• Both iptacopan and pegcetacoplan have been approved for other indications, providing an existing safety profile and real-world data from non-nephrology settings to guide early nephrology use.

Physicians should stay informed about the final FDA decision on pegcetacoplan and be prepared for its introduction into clinical practice, particularly in differentiating it from iptacopan based on administration method and individual patient needs.