Identification
- Summary
Pozelimab is a human monoclonal IgG4 antibody used to treat CD55-deficient protein-losing enteropathy (PLE) or CHAPLE disease
- Brand Names
- Veopoz
- Generic Name
- Pozelimab
- DrugBank Accession Number
- DB15218
- Background
CD55-deficient protein-losing enteropathy (PLE), or CHAPLE disease, is an ultra-rare hereditary disease, with fewer than 100 patients diagnosed worldwide or fewer than 10 patients in the US.7 The pathophysiology of this disease is mainly attributed to the deficiency of the CD55 protein, which is the main regulator of the complement cascade.1,2,3. Under normal circumstances, CD55 inhibits the activity of C3 and C5 convertases, thus preventing the cleavage of C3 and C5 respectively into immunoreactive peptides C3a and C5a.3 The loss of CD55 can therefore induce complement hyperactivation, causing the unwanted formation of membrane-attacking complex and resulting in paroxysmal nocturnal hemoglobinuria and complement-mediated autoimmune hemolysis that are often observed in CHAPLE disease.4
Pozelimab is a human, monoclonal immunoglobulin G4P antibody against the terminal complement protein C5.5 In August 18, 2023, pozelimab was approved by the FDA for the treatment of CHAPLE disease. It is currently the only treatment explicitly indicated for CHAPLE disease.6
- Type
- Biotech
- Groups
- Approved, Investigational
- Synonyms
- Pozelimab
- External IDs
- REGN3918
Pharmacology
- Indication
Pozelimab is indicated for the treatment of adult and pediatric patients 1 year of age and older with CD55-deficient protein-losing enteropathy (PLE), also known as CHAPLE disease.5
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 Chaple disease •••••••••••• •••••• ••••••••• ••••••••• - Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
The effect of pozelimab on complement activity was measured by the total complement hemolytic activity test (CH50). The magnitude and duration of reduction from baseline in CH50 by pozelimab were dose-dependent.5
In healthy subjects receiving a single dose of pozelimab 30 mg/kg administered as an intravenous infusion over approximately one hour, the complete inhibition of CH50 was achieved at the end of infusion in all subjects, was maintained for 28 days, and returned to baseline 84 days postdose. After a single dose of pozelimab administered as a 600 mg subcutaneous injection, the maximum reduction from baseline in CH50 was achieved 7 days post-dose in most subjects (range: 3 to 14 days), corresponding to Tmax, and returned to baseline 56 days post-dose.5
In patients with CD55-deficient PLE receiving a single 30 mg/kg dose administered as an intravenous infusion over approximately one hour followed by a weight-tiered subcutaneous injection once weekly starting at Week 1, CH50 was completely inhibited by Week 1 for most subjects and by Week 12 for all patients.5
In the same study of patients with CD55-deficient PLE, serum albumin concentrations increased as early as Week 1 and reached the normal range (≥3.5 g/dL) by Week 4 for most subjects and by Week 12 for all subjects. The serum albumin concentrations were maintained within the normal range for the duration of treatment. Endogenous serum IgG concentrations were also increased from baseline at Week 1 in all patients with CD55-deficient PLE and reached a stable concentration around Week 16.5
- Mechanism of action
Pozelimab-bbfg is a human, monoclonal immunoglobulin G4P (IgG4P) antibody directed against the terminal complement protein C5 that inhibits terminal complement activation by blocking cleavage of C5 into C5a (anaphylatoxin) and C5b, thereby blocking the formation of the membrane-attack complex (C5b-C9, a structure mediating cell lysis).5
Target Actions Organism AComplement C5 antibodyHumans - Absorption
In healthy subjects, single intravenous infusions of pozelimab over approximately one hour resulted in dose-proportional increases in mean Cmax, but greater than proportional increases in mean AUCinf (>16-fold) for total pozelimab concentrations in serum between 3 mg/kg and 30 mg/kg. The mean AUCinf increased by 3.5-fold between 10 mg/kg and 30 mg/kg. In healthy subjects, single subcutaneous injections of pozelimab resulted in an approximately 1.5-fold increase in mean Cmax and a 2.2-fold increase in mean AUCinf between 300 mg and 600 mg. Following subcutaneous injection of 600 mg, the bioavailability of pozelimab-bbfg is estimated as 51%. The median (range) time to reach peak concentration was 7 (3 to 7) days following a single subcutaneous injection of 300 mg or 600 mg.5
In patients with CD55-deficient protein-losing enteropathy, a single dose of pozelimab 30 mg/kg administered as an intravenous infusion over approximately one hour resulted in a median (range) total pozelimab trough concentration of 180 (52.8, 268) mg/L at Week 1. The predicted mean (SD) trough concentrations of total pozelimab at steady state are 330 (94.2) mg/L and 385 (112) mg/L for pozelimab 10 mg/kg or 12 mg/kg (up to a maximum 800 mg) once weekly via subcutaneous injection(s), respectively, following the intravenous loading dose. The steady-state total pozelimab concentrations were reached at approximately 20 weeks following subcutaneous injection once weekly.5
- Volume of distribution
In healthy adult subjects with a mean body weight of 70 kg, the mean (SD) volume of distribution following a single intravenous dose of 30 mg/kg was 3.3 (0.4) L. The mean (SD) apparent volume of distribution following a single subcutaneous injection of 300 mg and 600 mg was 6.0 (0.9) L and 8.6 (2.7) L, respectively.5
- Protein binding
There is limited information on the protein binding of pozelimab.
- Metabolism
Pozelimab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.5
- Route of elimination
Pozelimab elimination is mediated via linear and non-linear pathways. At higher concentrations, pozelimab elimination is primarily through the linear non-saturable proteolytic pathway, whereas at lower concentrations, the non-linear, saturable C5 target-mediated elimination predominates.5
- Half-life
In healthy adult subjects, the median (range) terminal half-life of total pozelimab in serum was 13.5 (10.0, 17.2) days following a single 30 mg/kg dose administered as an intravenous infusion. The median (range) terminal half-life was 14.1 (8.6, 17.3) days following a single 600 mg subcutaneous injection.5
- Clearance
There is limited information on the clearance of pozelimab.5
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Although there are no data on pozelimab use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes, monoclonal antibodies can be actively transported across the placenta.5
In an animal reproduction study in monkeys, pozelimab did not adversely affect embryofetal or postnatal development when administered from pregnancy confirmation through parturition at doses that produced exposure up to 3.3 to 3.8 times the predicted clinical exposures.5
Carcinogenicity studies have not been conducted with pozelimab. The mutagenic potential of pozelimab has not been evaluated; however, monoclonal antibodies are not expected to alter DNA or chromosomes.5
Fertility studies have not been conducted with pozelimab. In a 6-month toxicity study in sexually-mature male and female monkeys, pozelimab had no adverse effects on histological or functional markers of reproductive function (e.g., estrous cyclicity, testicular volume, ejaculate amount, total sperm count per ejaculate, sperm motility and morphology, and histology of reproductive organs) at doses up to 100 mg/kg/week (11.9 to 13.9-fold the predicted exposures at the recommended clinical doses, on an AUC basis).5
The most significant side effect of pozelimab is serious bacterial infections, particularly meningococcal infections due to the inhibition of the complement system. Meningococcal infections can deteriorate quickly if not detected and treated early; therefore, complete and updated or prophylaxis meningococcal vaccinations are recommended for patients according to the Advisory Committee on Immunization Practices (ACIP).5
- 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 softwareAbciximab The serum concentration of Pozelimab can be decreased when it is combined with Abciximab. Adalimumab The serum concentration of Pozelimab can be decreased when it is combined with Adalimumab. Aducanumab The serum concentration of Pozelimab can be decreased when it is combined with Aducanumab. Alemtuzumab The serum concentration of Pozelimab can be decreased when it is combined with Alemtuzumab. Alirocumab The serum concentration of Pozelimab can be decreased when it is combined with Alirocumab. - 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.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Veopoz Injection, solution 200 mg/1mL Intravenous; Subcutaneous Regeneron Pharmaceuticals, Inc. 2023-08-18 Not applicable US 
Categories
- Drug Categories
- Classification
- Not classified
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 0JJ21K6L2I
- CAS number
- 2096328-94-6
References
- General References
- Ozen A, Kasap N, Vujkovic-Cvijin I, Apps R, Cheung F, Karakoc-Aydiner E, Akkelle B, Sari S, Tutar E, Ozcay F, Uygun DK, Islek A, Akgun G, Selcuk M, Sezer OB, Zhang Y, Kutluk G, Topal E, Sayar E, Celikel C, Houwen RHJ, Bingol A, Ogulur I, Eltan SB, Snow AL, Lake C, Fantoni G, Alba C, Sellers B, Chauvin SD, Dalgard CL, Harari O, Ni YG, Wang MD, Devalaraja-Narashimha K, Subramanian P, Ergelen R, Artan R, Guner SN, Dalgic B, Tsang J, Belkaid Y, Ertem D, Baris S, Lenardo MJ: Broadly effective metabolic and immune recovery with C5 inhibition in CHAPLE disease. Nat Immunol. 2021 Feb;22(2):128-139. doi: 10.1038/s41590-020-00830-z. Epub 2021 Jan 4. [Article]
- Ozen A, Comrie WA, Ardy RC, Dominguez Conde C, Dalgic B, Beser OF, Morawski AR, Karakoc-Aydiner E, Tutar E, Baris S, Ozcay F, Serwas NK, Zhang Y, Matthews HF, Pittaluga S, Folio LR, Unlusoy Aksu A, McElwee JJ, Krolo A, Kiykim A, Baris Z, Gulsan M, Ogulur I, Snapper SB, Houwen RHJ, Leavis HL, Ertem D, Kain R, Sari S, Erkan T, Su HC, Boztug K, Lenardo MJ: CD55 Deficiency, Early-Onset Protein-Losing Enteropathy, and Thrombosis. N Engl J Med. 2017 Jul 6;377(1):52-61. doi: 10.1056/NEJMoa1615887. Epub 2017 Jun 28. [Article]
- Dho SH, Lim JC, Kim LK: Beyond the Role of CD55 as a Complement Component. Immune Netw. 2018 Feb 20;18(1):e11. doi: 10.4110/in.2018.18.e11. eCollection 2018 Feb. [Article]
- Ozen A: CHAPLE syndrome uncovers the primary role of complement in a familial form of Waldmann's disease. Immunol Rev. 2019 Jan;287(1):20-32. doi: 10.1111/imr.12715. [Article]
- FDA Approved Drug Products: VEOPOZ™ (pozelimab-bbfg) injection, for intravenous or subcutaneous use [Link]
- VEOPOZ™ (POZELIMAB-BBFG) RECEIVES FDA APPROVAL AS THE FIRST TREATMENT FOR CHILDREN AND ADULTS WITH CHAPLE DISEASE [Link]
- Veopoz™ (pozelimab-bbfg) Receives FDA Approval as the First Treatment for Children and Adults with CHAPLE Disease [Link]
- External Links
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 3 Recruiting Treatment Generalized Myasthenia Gravis 1 3 Recruiting Treatment Paroxysmal Nocturnal Haemoglobinuria (PNH) 2 3 Terminated Treatment Paroxysmal Nocturnal Haemoglobinuria (PNH) 2 2 Completed Treatment Paroxysmal Nocturnal Haemoglobinuria (PNH) 3 2, 3 Active Not Recruiting Treatment CHAPLE / CHAPLE disease 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Intravenous; Subcutaneous 200 mg/1mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antibody
- General Function
- Receptor binding
- Specific Function
- Activation of C5 by a C5 convertase initiates the spontaneous assembly of the late complement components, C5-C9, into the membrane attack complex. C5b has a transient binding site for C6. The C5b-C...
- Gene Name
- C5
- Uniprot ID
- P01031
- Uniprot Name
- Complement C5
- Molecular Weight
- 188303.705 Da
References
- FDA Approved Drug Products: VEOPOZ™ (pozelimab-bbfg) injection, for intravenous or subcutaneous use [Link]
Drug created at May 20, 2019 15:01 / Updated at September 02, 2023 05:02