Pegcetacoplan is a complement inhibitor indicated in the treatment of adults with paroxysmal nocturnal hemoglobinuria.

Brand Names
Generic Name
DrugBank Accession Number

Pegcetacoplan is a complement inhibitor indicated in the treatment of paroxysmal nocturnal hemoglobinuria (PNH).5,7 Prior to its FDA approval, patients with PNH were typically treated with the C5 inhibiting monoclonal antibody eculizumab.5 Patients given eculizumab experienced less hemolysis caused by the membrane attack complex, but were still somewhat susceptible to hemolysis caused by C3b opsonization.5,6 Pegcetacoplan was developed out of a need for an inhibitor of complement mediated hemolysis further upstream of C5.5,6 Pegcetacoplan is a pegylated C3 inhibitor that can disrupt the processes leading to both forms of hemolysis that threaten patients with PNH.5

Pegcetacoplan was granted FDA approval on 14 May 2021.7

  • Pegcetacoplan
External IDs
  • APL-2
  • WHO 10743



Pegcetacoplan is indicated to treat adults with paroxysmal nocturnal hemoglobinuria (PNH).7

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Associated Conditions
Contraindications & Blackbox Warnings
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Pegcetacoplan is a complement C3 inhibitor that prevents complement-mediated hemolysis of red blood cells in patients with paroxysomal nocturnal hemoglobinuria.7 It has a long duration of action as it is administered twice weekly.7 Patients should be vaccinated against encapsulated bacteria according to the most recent recommendations.7

Mechanism of action

PNH is due to a mutation in the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) gene.1,5 The mutation in the PIGA gene prevents an early step in the formation of glycosyl phosphatidyl inositol (GPI).1 Under normal circumstances, GPI connects cell surface proteins to the cell.1,5 In patients with PNH, complement inhibiting cell surface proteins, such as CD55 and CD59, are not anchored to the surface of red blood cells.1,5 In cases with reduced or absent CD55 and CD59, complement is not appropriately inhibited, leading to activation of the complement system and complement-mediated hemolysis.1,5 As a result of complement-mediated hemolysis, patients with PNH may experience anemia, fatigue, asthenia, and dyspnea.5

The alternative complement system pathway is spontaneously activated due to the absence of CD55, leading to activation of a C3 convertase that that cleaves C3 into C3a and C3b.1 C3b binds to factor B, which is cleaved by factor D into the smaller Ba and larger Bb.2 The resulting C3bBb can bind to other C3 proteins, leading to a positive feedback loop of complement activation.2 C3b proteins can also bind directly to a target cell, marking it as a target for phagocytosis.4 CD55, also known as decay-accelerating factor (DAF) disrupts the formation of C3bBb, preventing spontaneous activation of the alternative complement pathway.2

C3b cleaves C5 into C5a and C5b.1 C5b combines with complement proteins C6, C7, C8, and C9 to form the membrane attack complex (MAC).2 The MAC is a pore formed in the cell by 16 C9 proteins associated with C5b, C6, C7, and C8.3 Formation of pores destroys the cell membrane leading to cell death.3 CD59 disrupts the formation of the MAC, preventing hemolysis.1

In patients with PNH, extravascular hemolysis is mediated by C3b marking red blood cells for phagocytosis, and intravascular hemolysis is mediated by the MAC.5,7 Pegcetacoplan binds to C3 and C3b, reducing cleavage and activation of complement pathways, reducing both extravascular and intravascular hemolysis.7

AComplement C3

Pegcetacoplan has a median Tmax of 4.5-6.0 days.7 Patients reach steady state pharmacokinetics after 6-8 weeks.5

Volume of distribution

The volume of distribution in patients with PNH is 3.9 L.7

Protein binding

Not Available


Pegcetacoplan is expected to be metabolized to smaller oligopeptides and amino acids.7

Route of elimination

Not Available


The median half life in patients with PNH is 8.0 days.7


The mean clearance in patients with PNH is 0.37 L/day.7

Adverse Effects
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Data regarding overdoses in humans are not readily available.7 In the case of an overdose, patients should be treated with symptomatic and supportive measures.

Not Available
Pharmacogenomic Effects/ADRs
Not Available


Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Not Available
Food Interactions
No interactions found.


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International/Other Brands
Empaveli (Apellis Pharmaceuticals, Inc.)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
AspaveliInjection, solution1080 mgSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2022-01-20Not applicableEU flag
AspaveliInjection, solution1080 mgSubcutaneousSWEDISH ORPHAN BIOVITRUM AB (PUBL)2022-01-20Not applicableEU flag
EmpaveliInjection, solution1080 mg/20mLSubcutaneousApellis Pharmaceuticals, Inc.2021-05-14Not applicableUS flag


Drug Categories
Not classified
Affected organisms
  • Humans

Chemical Identifiers

CAS number


General References
  1. Fattizzo B, Serpenti F, Giannotta JA, Barcellini W: Difficult Cases of Paroxysmal Nocturnal Hemoglobinuria: Diagnosis and Therapeutic Novelties. J Clin Med. 2021 Mar 1;10(5). pii: jcm10050948. doi: 10.3390/jcm10050948. [Article]
  2. Dobo J, Kocsis A, Gal P: Be on Target: Strategies of Targeting Alternative and Lectin Pathway Components in Complement-Mediated Diseases. Front Immunol. 2018 Aug 8;9:1851. doi: 10.3389/fimmu.2018.01851. eCollection 2018. [Article]
  3. Tomita M: Biochemical background of paroxysmal nocturnal hemoglobinuria. Biochim Biophys Acta. 1999 Oct 8;1455(2-3):269-86. doi: 10.1016/s0925-4439(99)00068-x. [Article]
  4. Baudino L, Sardini A, Ruseva MM, Fossati-Jimack L, Cook HT, Scott D, Simpson E, Botto M: C3 opsonization regulates endocytic handling of apoptotic cells resulting in enhanced T-cell responses to cargo-derived antigens. Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1503-8. doi: 10.1073/pnas.1316877111. Epub 2014 Jan 13. [Article]
  5. de Castro C, Grossi F, Weitz IC, Maciejewski J, Sharma V, Roman E, Brodsky RA, Tan L, Di Casoli C, El Mehdi D, Deschatelets P, Francois C: C3 inhibition with pegcetacoplan in subjects with paroxysmal nocturnal hemoglobinuria treated with eculizumab. Am J Hematol. 2020 Nov;95(11):1334-1343. doi: 10.1002/ajh.25960. Epub 2020 Sep 11. [Article]
  6. Hillmen P, Szer J, Weitz I, Roth A, Hochsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro C, Nishimori H, Tan L, Hamdani M, Deschatelets P, Francois C, Grossi F, Ajayi T, Risitano A, de la Tour RP: Pegcetacoplan versus Eculizumab in Paroxysmal Nocturnal Hemoglobinuria. N Engl J Med. 2021 Mar 18;384(11):1028-1037. doi: 10.1056/NEJMoa2029073. [Article]
  7. FDA Approved Drug Products: Empaveli (Pegcetacoplan) Subcutaneous Injection [Link]
  8. Press Release: pegcetacoplan EMA approval [Link]

Clinical Trials

Clinical Trials
3Active Not RecruitingTreatmentMacular Degeneration, Dry2
3Active Not RecruitingTreatmentPNH1
3CompletedTreatmentParoxysmal Nocturnal Haemoglobinuria (PNH)2
3Enrolling by InvitationTreatmentGeographic Atrophy Secondary to Age-related Macular Degeneration1
3RecruitingTreatmentC3 Glomerulonephritis / C3G / Complement 3 Glomerulonephritis / Complement 3 Glomerulopathy (C3G) / DDD / Dense Deposit Disease (DDD) / IC-MPGN / Immune Complex Membranoproliferative Glomerulonephritis (IC-MPGN) / Membranoproliferative Glomerulonephritis (MPGN)1
3RecruitingTreatmentCold Agglutinin Disease (CAD)1
2Active Not RecruitingTreatmentAmyotrophic Lateral Sclerosis (ALS) / Motor Neurone Disease1
2Active Not RecruitingTreatmentC3 Glomerulonephritis / Dense Deposit Disease (DDD) / Glomerulonephritis, Membranous / IgA Nephropathy (IgAN) / Lupus Nephritis1
2Active Not RecruitingTreatmentCold Agglutinin Disease (CAD) / Warm Autoimmune Hemolytic Anemia (WAIHA)1
2CompletedTreatmentMacular Degeneration, Dry1


Not Available
Not Available
Dosage Forms
Injection, solutionSubcutaneous1080 mg
Injection, solutionSubcutaneous1080 mg/20mL
Not Available
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US10875893No2020-12-292033-11-15US flag
US9169307No2015-10-272027-11-18US flag
US7989589No2011-08-022027-12-04US flag
US10125171No2018-11-132033-08-02US flag
US10035822No2018-07-312033-11-15US flag
US7888323No2011-02-152027-12-04US flag
US11040107No2021-06-222038-04-09US flag
US11292815No2013-11-152033-11-15US flag


Experimental Properties
Not Available


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Pharmacological action
General Function
Receptor binding
Specific Function
C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C...
Gene Name
Uniprot ID
Uniprot Name
Complement C3
Molecular Weight
187146.73 Da
  1. FDA Approved Drug Products: Empaveli (Pegcetacoplan) Subcutaneous Injection [Link]

Drug created at May 17, 2021 19:14 / Updated at December 17, 2021 21:23