Notes on Targeted Conditions

Paroxysmal Nocturnal Hemoglobinuria (PNH)

  • PNH affects between 1 and 5 people per million.
  • The annual cost of current complement-targeted therapy for PNH exceeds $400,000 per patient.
  • Anti-C5 therapy is not satisfactory in all PNH patients, and the only curative treatment for PNH, which is bone marrow transplantation, has been associated with complications; allogeneic bone marrow transplantation has been associated with significant morbidity and mortality.


Age-Related Macular Degeneration (AMD)

  • Around the world, there are 3 million people who have been diagnosed with AMD in at least one eye, while this group is on course to doubling by 2020.
  • In the Western world, macular degeneration is the #1 cause for vision loss in those over 65 years old, and, in other parts of the world, the prevalence for this disease is going up.
  • Local inhibition of complement activation is thought to hold promise for the treatment of both dry and wet AMD. Compstatin was the first complement-specific candidate entering clinical trials for this.



  • Over 500,000 individuals need to undergo kidney replacement therapy for end-stage renal disease (ERSD) in the United States, but only 3.5% are able to undergo transplantation. The majority of patients rely on hemodialysis.
  • 35% of those undergoing hemodialysis have a 5-year survival rate.
  • Even though hemodialysis techniques and materials have been improved, the mortality rate for patients treated with hemodialysis is around 16%.
  • In 2009, the cost for treating ESRD patients in the U.S. amounted to over $40 billion in public and private funds, according to National Kidney and Urologic Diseases Information Clearinghouse (NKUDIC).


Ischemia/Reperfusion (I/R) Injuries and Transplantation

  • Ischemic injury affects 1.3 million people in the U.S. each year (in the form of myocardial infarction, stroke, and other thrombotic events).
  • Complement activation in I/R injury as it takes place during myocardial infarction was first described more than 40 years ago.
  • Experimental studies in various organ systems and clinical trials have pointed to the inhibition of the complement system as a potential means for decreasing harmful tissue injury in I/R conditions.
  • Studies have indicated that complement proteins have an important role in organ damage after transplantation (via modulation of the activation of the adaptive immune response and ischemia/reperfusion).



DeAngelis, R. A., Reis, E. S., Ricklin, D., & Lambris, J. D. (2012). Targeted complement inhibition as a promising strategy for preventing inflammatory complications in hemodialysis. Immunobiology, 217(11), 1097-1105.

Elham, A., Wuding, Z., & Steven, S. (2010). Complement in organ transplantation. Current opinion in organ transplantation, 15(4), 486.

Garland, D. L., Fernandez-Godino, R., Kaur, I., Speicher, K.D., Harnly, J.M., Lambris, J.D., Speicher, D.W., & Pierce, E.A. (2013). Mouse genetics and proteomic analyses demonstrate a critical role for complement in a model of DHRD/ML, an inherited macular degeneration. Human molecular genetics (2013): ddt395.

Hajishengallis G, Abe T, Maekawa T, Hajishengallis E, Lambris JD. (2013). Role of complement in host-microbe homeostasis of the periodontium. Seminars in Immunology 25: 65-72.

Mastellos, D. C., Ricklin, D., Yancopoulou, D., Risitano, A., & Lambris, J. D. (2014). Complement in paroxysmal nocturnal hemoglobinuria: exploiting our current knowledge to improve the treatment landscape. Expert review of hematology, 7(5), 583-598.

Reis, E. S., DeAngelis, R. A., Chen, H., Resuello, R. R., Ricklin, D., & Lambris, J. D. (2014). Therapeutic C3 inhibitor Cp40 abrogates complement activation induced by modern hemodialysis filters. Immunobiology.

Ricklin D, Lambris JD. (2013). Complement in immune and inflammatory disorders: pathophysiological mechanisms. Journal of Immunology 190: 3831-8.

Ricklin D, Lambris JD. (2013). Complement in immune and inflammatory disorders: therapeutic interventions. Journal of Immunology 190: 3839-47.

Ricklin, D., & Lambris, J. D. (2008). Compstatin: a complement inhibitor on its way to clinical application. In Current Topics in Complement II (pp. 262-281). Springer US.

Riedemann, N. C., & Ward, P. A. (2003). Complement in ischemia reperfusion injury. The American journal of pathology, 162(2), 363-367.

Risitano, A. M., & Rotoli, B. (2008). Paroxysmal nocturnal hemoglobinuria: pathophysiology, natural history and treatment options in the era of biological agents. Biologics: targets & therapy, 2(2), 205.

Schmier, J. K., & Levine, J. A. (2013). Economic impact of progression of age-related macular degeneration. US Ophthalmic Review, 6(1):52-57.

Vascular Stem Cell Therapy. (2014). In A. Mohamed & N. Mariam (Eds.), Stem Cells and Cell Therapy (1st ed., Vol. 8, p. 50). Springer Netherlands.