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Identification
- Summary
Pegcetacoplan is a complement inhibitor indicated in the treatment of adults with paroxysmal nocturnal hemoglobinuria.
- Brand Names
- Empaveli, Syfovre
- Generic Name
- Pegcetacoplan
- DrugBank Accession Number
- DB16694
- Background
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 for subcutaneous use was granted FDA approval on 14 May 2021.7 In February 2023, pegcetacoplan for intravitreal use was approved by the FDA for the treatment of geographic atrophy (GA) secondary to age-related macular degeneration.10
- Type
- Biotech
- Groups
- Approved
- Synonyms
- Pegcetacoplan
- External IDs
- APL-2
- WHO 10743
Pharmacology
- Indication
Pegcetacoplan is indicated to treat adults with paroxysmal nocturnal hemoglobinuria (PNH).7 It is also indicated to treat geographic atrophy (GA) secondary to age-related macular degeneration.10
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Associated Conditions
Indication Type Indication Combined Product Details Approval Level Age Group Patient Characteristics Dose Form Treatment of Geographic atrophy secondary to age-related macular degeneration •••••••••••• ••••••••• Treatment of Paroxysmal nocturnal haemoglobinuria (pnh) •••••••••••• ••••• •••••••••• •• •• •••••••••• ••••••••• Treatment of Paroxysmal nocturnal haemoglobinuria (pnh) •••••••••••• ••••• •••••••••• •••••••• •• •• •••••••••• ••••••••• Treatment of Paroxysmal nocturnal haemoglobinuria (pnh) •••••••••••• ••••• ••••••• ••••• ••••••••• •••• • •• ••••••••• ••• •• ••••• ••••• •••••• ••••••••• Treatment of Paroxysmal nocturnal haemoglobinuria (pnh) •••••••••••• ••••• ••••••••• - 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
Target Actions Organism AComplement C3 binderregulatorHumans - Absorption
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
- Metabolism
Pegcetacoplan is expected to be metabolized to smaller oligopeptides and amino acids.7
- Route of elimination
Studies done in cynomolgus monkeys given radiolabeled pegcetacoplan suggest that the labelled peptide moiety is mainly excreted through urine. The elimination of PEG was not evaluated; however, it is known that it undergoes renal excretion.9
- Half-life
The median half life in patients with PNH is 8.0 days.7
- Clearance
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.
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Pegcetacoplan. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Pegcetacoplan. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Pegcetacoplan. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Pegcetacoplan. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Pegcetacoplan. - Food Interactions
- No interactions found.
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- International/Other Brands
- Empaveli (Apellis Pharmaceuticals, Inc.)
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Aspaveli Injection, solution 1080 mg Subcutaneous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2022-01-20 Not applicable EU 
Aspaveli Injection, solution 1080 mg Subcutaneous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2022-01-20 Not applicable EU Empaveli Injection, solution 1080 mg/20mL Subcutaneous CENEXI HSC 2021-05-14 Not applicable US 
Empaveli Injection, solution 1080 mg/20mL Subcutaneous Apellis Pharmaceuticals, Inc. 2021-05-14 Not applicable US Empaveli Solution 1080 mg / 20 mL Subcutaneous SWEDISH ORPHAN BIOVITRUM AB (PUBL) 2023-02-15 Not applicable Canada 
Categories
- ATC Codes
- S01XA31 — Pegcetacoplan
- S01XA — Other ophthalmologicals
- S01X — OTHER OPHTHALMOLOGICALS
- S01 — OPHTHALMOLOGICALS
- S — SENSORY ORGANS
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Humans
Chemical Identifiers
- UNII
- TO3JYR3BOU
- CAS number
- 2019171-69-6
References
- General References
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- FDA Approved Drug Products: Empaveli (Pegcetacoplan) Subcutaneous Injection [Link]
- Press Release: pegcetacoplan EMA approval [Link]
- Health Canada Approved Drug Products: EMPAVELI (pegcetacoplan) injection solution for subcutaneous infusion use [Link]
- FDA Approved Drug Products: SYFOVRE (pegcetacoplan) injection for intravitreal use (February 2023) [Link]
- External Links
- KEGG Drug
- D11613
- 2557372
- Wikipedia
- Pegcetacoplan
Clinical Trials
- Clinical Trials
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Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 1080 mg Injection, solution Subcutaneous 1080 mg/20mL Solution Subcutaneous 1080 mg / 20 mL Injection, solution Intravitreal 15 mg/0.1mL - Prices
- Not Available
- Patents
Patent Number Pediatric Extension Approved Expires (estimated) Region US10875893 No 2020-12-29 2033-11-15 US US9169307 No 2015-10-27 2027-11-18 US US7989589 No 2011-08-02 2027-12-04 US US10125171 No 2018-11-13 2033-08-02 US US10035822 No 2018-07-31 2033-11-15 US US7888323 No 2011-02-15 2027-12-04 US US11040107 No 2021-06-22 2038-04-09 US US11292815 No 2013-11-15 2033-11-15 US US8168584 No 2012-05-01 2027-04-07 US US9056076 No 2015-06-16 2026-10-25 US US11661441 No 2013-01-13 2033-01-13 US US11844841 No 2018-12-09 2038-12-09 US US11903994 No 2017-02-22 2037-02-22 US
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- BinderRegulator
- General 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 C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates
- Specific Function
- C5l2 anaphylatoxin chemotactic receptor binding
- Gene Name
- C3
- Uniprot ID
- P01024
- Uniprot Name
- Complement C3
- Molecular Weight
- 187146.73 Da
References
- FDA Approved Drug Products: Empaveli (Pegcetacoplan) Subcutaneous Injection [Link]
Drug created at May 17, 2021 19:14 / Updated at August 09, 2023 00:07