Disease classification determines therapy

People with subclinical PNH require no specific treatment. For people with PNH associated with another bone marrow failure, therapy should primarily target the underlying syndrome. For people with classic PNH, complement inhibitors are utilised in regions where they are accessible.1

C5 inhibitors

C5 inhibitors bind to the C5 fragment and inhibit its cleavage to prevent membrane attack complex (MAC) formation, allowing PNH red blood cells to avoid complement-mediated lysis. These inhibitors effectively reduce excess haemolysis and thrombotic complications and significantly extend survival.2

Treatment with complement inhibitors can cause life-threatening infections with N. meningitidis and other encapsulated organisms. Meningococcal vaccination is mandatory before treatment initiation with C5 inhibitors.1,3

Other complement inhibitors

Proximal complement inhibitors target proteins upstream in the complement pathway, such as C3 and Factor B. They can address the needs of people with notable extravascular haemolysis.4,5

Complement inhibitors to treat PNH

Unmet needs with current treatments

Despite the clinical benefits, breakthrough haemolysis may occur in patients with PNH due to incomplete complement inhibition.

The frequent dosing schedules and the need for intravenous infusions associated with current complement inhibitors contribute to a considerable treatment burden for people with PNH.2,4,6,7

While current complement inhibitors have transformed PNH treatment, challenges such as treatment burden, accessibility issues and genetic variations persist. Ongoing research into new therapeutic options with reduced burden and improved efficacy remains crucial in addressing the unmet needs of individuals living with PNH.

Existing unmet needs in PNH

PNH Treatments

Sufficient complement inhibition with no breakthrough haemolysis


PNH Treatments

Greater treatment convenience /reduced treatment burden


PNH Treatments

Effective treatment for patients with C5 SNP R885H for whom approved C5 inhibitors are ineffective


PNH Treatments

Increased access to effective treatments for all patients


Explore other PNH resources


  1. Parker CJ. Update on the diagnosis and management of paroxysmal nocturnal hemoglobinuria. Hematology Am Soc Hematol Educ Program. 2016; 2016 (1): 208–216. doi:10.1182/asheducation-2016.1.208
  2. Risitano AM, Marotta S, Ricci P et al. Anti-complement treatment for paroxysmal nocturnal hemoglobinuria: time for proximal complement inhibition? A position paper from the SAAWP of the EBMT. Front Immunol. 2019; 10: 1157. doi:10.3389/fimmu.2019.01157
  3. Brodsky RA. Paroxysmal nocturnal hemoglobinuria. Blood. 2014; 124 (18): 2804–2811. doi:10.1182/blood-2014-02-522128
  4. Nishimura J, Yamamoto M, Hayashi S et al. Genetic variants in C5 and poor response to eculizumab. N Engl J Med. 2014; 370 (7): 632–639. doi:10.1056/NEJMoa1311084
  5. Kulasekararaj AG, Kuter DJ, Griffin M et al. Biomarkers and laboratory assessments for monitoring the treatment of patients with paroxysmal nocturnal hemoglobinuria: Differences between terminal and proximal complement inhibition. Blood Rev. 2023; 59: 101041. doi:10.1016/j.blre.2023.101041
  6. Lee JW, Sicre de Fontbrune F, Wong Lee Lee L et al. Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study. Blood. 2019; 133 (6): 530–539. doi:10.1182/blood-2018-09-876136
  7. Panse J. Paroxysmal nocturnal hemoglobinuria: Where we stand. Am J Hematol. 2023; 98 (Suppl 4): S20–S32. doi:10.1002/ajh.26832

Welcome to Medically

The Roche Science Hub

This website is a non-promotional global resource intended to facilitate transparent scientific exchange regarding developments in medical research, diagnostics, and disease management. It is intended for healthcare professionals.

Not a healthcare professional? Browse:

This global website is intended for healthcare professionals outside the UK, US, Canada and Australia. The content on this website may include scientific information about experimental or investigational compounds, indications and services that are not approved or valid in your jurisdiction. Registration status and prescribing information of medicinal products may differ between countries. Please refer to local product information for any medicinal products mentioned on this website. Information available on this website does not constitute professional medical advice, and Roche and Genentech accept no responsibility for access to or use of the same.

You are Leaving Medically

By following this link, you are leaving Roche Website and entering a site that is not owned or controlled by Roche. Roche does not take any responsibility for acces to or use of this website, nor for any content therein.