Paroxysmal Nocturnal Hemoglobinuria

Iptacopan

Complement Factor B Inhibitor

Table of contents

What is iptacopan used for?

Targets Factor B in the alternative complement pathway, reducing red blood cell destruction and kidney damage.

Treats 3 conditions:

PNH - Rare blood disorder where red blood cells (RBC) break down prematurely, causing anaemia and clotting risks. 

IgAN - Kidney disease with protein leakage due to immune attacks on kidney filters.

C3G Ultra - rare kidney disease causing inflammation and progression to kidney failure.

What is the mechanism of action of iptacopan?

Blocks the alternative complement pathway, preventing C3 protein buildup in kidneys and RBC destruction

Reduces both intravascular (bloodstream) and extravascular (organ-based) RBC breakdown in PNH.

Lowers urinary protein levels in IgAN and C3G by targeting the disease’s root cause.

What are the contraindications of iptacopan?

Delay treatment in Patients with an active severe infection (e.g., sepsis), until resolved.

Avoid prescribing to patients who are unvaccinated against encapsulated bacteria (e.g., Streptococcus pneumoniae, Neisseria meningitidis).

Use caution in patients with severe liver disease due to limited safety data in this population.

Important iptacopan prescribing safety information.

Administer vaccines for encapsulated bacteria at least 2 weeks before initiating therapy.

Monitor lipid levels regularly, as treatment may increase cholesterol or triglycerides.

Enroll patients in the Fabhalta REMS program to ensure compliance with safety protocols.

Avoid abrupt discontinuation in PNH patients to prevent rebound haemolysis.

Iptacopan patient counselling advice.

Report symptoms immediately - Fever, jaundice, dark urine, or breathing issues.

Carry the safety card - Highlights infection risks during and 2 weeks post-treatment.

Adhere to dosing - Skipping doses may worsen PNH or kidney disease.

References


  1. Barratt, J., Rovin, B., Zhang, H., Kashihara, N., Maes, B., Rizk, D., Trimarchi, H., Sprangers, B., Meier, M., Kollins, D., Wang, W., Magirr, A. and Perkovic, V. (2022). POS-546 EFFICACY AND SAFETY OF IPTACOPAN IN IgA NEPHROPATHY: RESULTS OF A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED PHASE 2 STUDY AT 6 MONTHS. Kidney International Reports, 7(2), p.S236. doi:https://doi.org/10.1016/j.ekir.2022.01.577. Link

  2. Bomback, A.S., Kavanagh, D., Vivarelli, M., Meier, M., Wang, Y., Webb, N.J.A., Trapani, A.J. and Smith, R.J.H. (2022). Alternative Complement Pathway Inhibition with Iptacopan for the Treatment of C3 Glomerulopathy-Study Design of the APPEAR-C3G Trial. Kidney International Reports. doi:https://doi.org/10.1016/j.ekir.2022.07.004. Link

  3. Carlos and Patel, B.J. (2024). Iptacopan for the Treatment of Paroxysmal Nocturnal Hemoglobinuria. Expert Opinion on Pharmacotherapy, pp.1–9. doi:https://doi.org/10.1080/14656566.2024.2404110. Link

  4. FDA (2025). Fabhalta Approved for Complement 3 Glomerulopathy. [online] U.S. Food and Drug Administration. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-first-treatment-adults-complement-3-glomerulopathy-rare-kidney-disease-reduce [Accessed 21 Apr. 2025]. Link
  5. Novartis (n.d.). HIGHLIGHTS OF PRESCRIBING INFORMATION. [online] Available at: https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf [Accessed 21 Apr. 2025]. Link