Targeted Immune Intervention: How does Eculizumab work?

October 8, 2025 •

4 min read

Without treatment from complement inhibitors, the 10-year survival rate for patients with Paroxysmal Nocturnal Hemoglobinuria (PNH) is just 65% [1.3.3]. Eculizumab revolutionized treatment for this and other rare diseases. But how does Eculizumab work to achieve this?

Quick Summary

Eculizumab is a monoclonal antibody that targets and inhibits the C5 protein of the complement system. This action prevents the formation of the destructive membrane attack complex (MAC), halting cell damage in specific autoimmune disorders.

Key Points

Core Mechanism: Eculizumab is a monoclonal antibody that binds to the complement protein C5, blocking its cleavage [1.2.1].
Terminal Complement Inhibition: By blocking C5 cleavage, Eculizumab prevents the formation of the inflammatory C5a molecule and the cell-destroying C5b-9 Membrane Attack Complex (MAC) [1.2.3].
Approved Indications: It is approved for Paroxysmal Nocturnal Hemoglobinuria (PNH), Atypical Hemolytic Uremic Syndrome (aHUS), generalized Myasthenia Gravis (gMG), and Neuromyelitis Optica Spectrum Disorder (NMOSD) [1.5.4].
Major Risk: The primary risk is a significantly increased susceptibility to serious meningococcal infections, requiring mandatory vaccination [1.6.2].
Administration: The drug is given via intravenous (IV) infusion, typically every two weeks for maintenance therapy [1.5.5].
Disease Impact: In PNH, it halts intravascular hemolysis, and in aHUS, it inhibits complement-mediated thrombotic microangiopathy [1.2.1].
Neurological Impact: In gMG and NMOSD, it is presumed to work by reducing complement-mediated damage at the neuromuscular junction and in the central nervous system, respectively [1.2.1].

Understanding the Complement System: The Body's Double-Edged Sword

The complement system is a vital part of the innate immune system, a complex network of over 50 proteins that helps defend the body against pathogens like bacteria [1.4.1]. This system can be activated through three main pathways: the classical, lectin, and alternative pathways [1.4.1]. While distinct at their start, all three pathways converge, leading to the activation of a crucial protein called complement component 5, or C5 [1.4.3].

The activation of C5 is a pivotal step. A C5 convertase enzyme cleaves C5 into two potent fragments: C5a and C5b [1.2.2, 1.4.2].

C5a is a powerful anaphylatoxin that promotes inflammation and attracts immune cells (chemotaxis) to the site of an infection or injury [1.4.2, 1.4.3].
C5b initiates the final, destructive phase of the complement cascade. It triggers the assembly of the Membrane Attack Complex (MAC), also known as C5b-9 [1.4.3]. The MAC is a pore-forming structure that can puncture the membranes of target cells, leading to their lysis (destruction) [1.2.3, 1.4.2].

In healthy individuals, this system is tightly regulated to attack foreign invaders while sparing the body's own cells. However, in certain autoimmune diseases, this regulation fails, and the complement system begins to attack healthy tissues, causing significant damage [1.3.3].

The Core Mechanism: How Does Eculizumab Work?

Eculizumab (brand name Soliris) is a humanized monoclonal antibody designed specifically to interrupt this destructive process [1.2.3]. Its mechanism of action is highly targeted and precise.

Eculizumab works by binding with high affinity and specificity to the complement protein C5 [1.2.1, 1.3.3]. By attaching to C5, eculizumab physically blocks its cleavage into C5a and C5b [1.2.2]. This steric hindrance prevents the C5 convertase enzyme from accessing its target [1.3.3].

By halting the cleavage of C5, eculizumab achieves two critical therapeutic effects:

It prevents the generation of the pro-inflammatory C5a peptide, reducing the inflammatory signaling that contributes to tissue damage [1.2.3].
It stops the formation of the C5b fragment, which in turn prevents the assembly of the terminal complement complex C5b-9 (the MAC) [1.2.1].

This inhibition of the terminal complement pathway is the key to eculizumab's effectiveness. It doesn't affect the earlier parts of the complement cascade, which remain available for immune defense, but it shuts down the final, cell-destroying step that causes pathology in certain diseases [1.2.3].

Conditions Treated with Eculizumab

Eculizumab is FDA-approved for several rare, life-threatening diseases characterized by complement-mediated damage [1.5.2, 1.5.4]:

Paroxysmal Nocturnal Hemoglobinuria (PNH): In PNH, a genetic mutation results in red blood cells lacking protective proteins like CD59, making them vulnerable to MAC-mediated destruction (intravascular hemolysis) [1.2.2]. Eculizumab stops this hemolysis, reducing anemia, thrombosis risk, and improving survival rates to near that of the general population [1.3.1, 1.8.3].
Atypical Hemolytic Uremic Syndrome (aHUS): In aHUS, uncontrolled complement activation leads to the formation of blood clots in small blood vessels throughout the body (thrombotic microangiopathy or TMA), particularly affecting the kidneys [1.2.1]. Eculizumab inhibits this complement-mediated TMA, improving platelet counts and renal function [1.3.2].
Generalized Myasthenia Gravis (gMG): In patients who are anti-acetylcholine receptor (AChR) antibody positive, the complement system is activated at the neuromuscular junction, damaging it and impairing nerve-muscle communication [1.2.5]. Eculizumab is thought to reduce this C5b-9 deposition, improving muscle strength and quality of life [1.2.1, 1.3.3].
Neuromyelitis Optica Spectrum Disorder (NMOSD): For patients who are anti-aquaporin-4 (AQP4) antibody positive, the binding of these antibodies to astrocytes in the central nervous system triggers complement activation and subsequent inflammation and damage [1.2.5]. Eculizumab inhibits this process, significantly reducing relapse rates [1.2.1, 1.2.5].

Administration, Risks, and Monitoring

Eculizumab is administered intravenously (IV) [1.9.4]. The dosing schedule typically begins with a weekly induction phase for four weeks, followed by a maintenance dose every two weeks [1.5.5].

Black Box Warning and Key Risks

The most significant risk associated with eculizumab is an increased susceptibility to serious infections, particularly from encapsulated bacteria like Neisseria meningitidis [1.6.2]. This is because the terminal complement pathway is essential for defending against these specific pathogens. The FDA has issued a Boxed Warning for this risk [1.5.4].

To mitigate this, patients must be vaccinated against meningococcal disease at least two weeks before their first dose of eculizumab [1.5.5, 1.6.2]. Other common side effects include headache, nasopharyngitis, back pain, and nausea [1.5.4, 1.6.3].

Patients are monitored closely during and after infusions for any adverse reactions [1.9.4]. Regular blood tests, such as a complete blood count and comprehensive metabolic panel, are recommended to monitor for side effects and disease activity [1.9.1].

Comparison of Complement C5 Inhibitors

Eculizumab paved the way for other C5 inhibitors with different properties, such as Ravulizumab.


Feature	Eculizumab (Soliris)	Ravulizumab (Ultomiris)
Mechanism	Monoclonal antibody that binds to C5, preventing its cleavage [1.2.1].	A derivative of eculizumab with amino acid substitutions, also binds C5 [1.7.1].
Half-Life	Shorter half-life, approximately 11 days [1.2.3].	Longer half-life due to recycling via the neonatal Fc receptor (FcRn) [1.7.1, 1.7.3].
Dosing Frequency	Intravenous infusion every 2 weeks (maintenance) [1.5.5].	Intravenous infusion every 8 weeks (maintenance) [1.7.2].
Efficacy	Clinically effective in treating PNH, aHUS, gMG, and NMOSD [1.5.4].	Clinically non-inferior to eculizumab for PNH and aHUS [1.7.2, 1.7.4].
Patient Preference	Less preferred due to frequent infusions causing more disruption to daily life [1.7.4].	Highly preferred by patients and caregivers due to less frequent infusions [1.7.4].
Cost	High treatment cost, but Ravulizumab may be more cost-saving over time due to fewer administrations [1.11.3, 1.7.2].	Overall lower total treatment costs compared to eculizumab, making it a more cost-effective option in some analyses [1.7.2, 1.11.3].

Conclusion

Eculizumab works by precisely targeting and inhibiting the complement protein C5, thereby preventing the formation of the inflammatory C5a peptide and the cell-destroying C5b-9 MAC [1.2.1, 1.2.3]. This targeted intervention effectively halts the underlying mechanism of tissue damage in diseases like PNH, aHUS, gMG, and NMOSD. While it carries a significant risk of certain infections that necessitates careful risk mitigation, its development represents a landmark achievement in pharmacology, transforming the prognosis for patients with these rare and severe complement-mediated disorders [1.8.3]. The evolution of this therapy into longer-acting agents like ravulizumab continues to improve patient quality of life by reducing treatment burden [1.7.4].

For more information from an authoritative source, you can visit the FDA's page on Eculizumab [1.5.5].

Frequently Asked Questions

Eculizumab, sold under the brand name Soliris, is a prescription medication used to treat rare diseases like PNH, aHUS, gMG, and NMOSD. It is a monoclonal antibody that works by inhibiting a specific part of the immune system called the complement system [1.5.1, 1.2.3].

In Paroxysmal Nocturnal Hemoglobinuria (PNH), red blood cells are missing a protective protein, making them vulnerable to attack by the complement system's Membrane Attack Complex (MAC). Eculizumab binds to the C5 protein, preventing the MAC from forming and thereby stopping the destruction (hemolysis) of red blood cells [1.2.1, 1.2.2].

The most serious risk is an increased susceptibility to life-threatening meningococcal infections caused by the bacteria Neisseria meningitidis. The drug carries a Boxed Warning for this risk, and patients must be vaccinated against meningitis before starting treatment [1.5.4, 1.6.2].

Eculizumab is administered as an intravenous (IV) infusion by a healthcare professional. For adults, this typically involves a weekly loading dose for the first four weeks, followed by a maintenance infusion every two weeks [1.5.5, 1.9.4].

No, Eculizumab is not chemotherapy. It is a targeted therapy known as a monoclonal antibody that selectively inhibits a specific protein (C5) in the complement system. It does not have the widespread effects on cell division that are characteristic of traditional chemotherapy [1.2.3].

It is important to receive Eculizumab at the recommended time points. If a dose is missed, you should contact your healthcare provider immediately to reschedule. Administering the dose within two days of the scheduled time point is generally acceptable, but your doctor will provide specific guidance [1.5.5].

Discontinuation of Eculizumab must be done under the close supervision of a physician. Stopping the treatment can lead to a return of severe disease symptoms, such as hemolysis in PNH or thrombotic microangiopathy in aHUS [1.10.1, 1.6.4]. The risk of relapse may be higher in patients with certain genetic mutations [1.10.2].