Ravulizumab
Identification
- Summary
Ravulizumab is a monoclonal antibody used to treat paroxysmal nocturnal hemoglobinuria, atypical hemolytic uremic syndrome, and myasthenia gravis.
- Brand Names
- Ultomiris
- Generic Name
- Ravulizumab
- DrugBank Accession Number
- DB11580
- Background
Ravulizumab is a potent and selective complement 5 (C5) inhibitor. It is a humanized monoclonal IgG2/4 kappa antibody produced in Chinese hamster ovary (CHO) cells.4 Ravulizumab was engineered from eculizumab, another complement inhibitor, to increase the duration of action and reduce the frequency of drug administration.1 It works by blocking terminal complement-mediated inflammation, cell activation, and cell lysis in blood disorders associated with the destruction of red blood cells, thrombosis, and impaired bone marrow function.2
Ravulizumab was first approved by the FDA on December 21, 2018, for the treatment of paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome in children and adults.2 It was later approved by the European Commission on July 2, 2019, for the same indications.6 Ravulizumab is also used to treat myasthenia gravis.4,5 Ravulizumab is currently being investigated for the treatment of Coronavirus disease (COVID-19)-induced microvasculature injury and endothelial damage leading to thrombotic microangiopathy (TMA) causing acute kidney injury (AKI).7
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- C6430H9888N1696O2028S48
- Protein Average Weight
- 148000.0 Da (approximate)
- Sequences
>A Chain XVQLVQSGAEVKKPGASVKVSCKASGHIFSNYWIQWVRQAPGQGLEWMGEILPGSGHTEY TENFKDRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARYFFGSSPNWYFDVWGQGTLVTV SSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVLHEALHSHYTQKSLSLSLG
>B Chain XVQLVQSGAEVKKPGASVKVSCKASGHIFSNYWIQWVRQAPGQGLEWMGEILPGSGHTEY TENFKDRVTMTRDTSTSTVYMELSSLRSEDTAVYYCARYFFGSSPNWYFDVWGQGTLVTV SSASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ SSGLYSLSSVVTVPSSNFGTQTYTCNVDHKPSNTKVDKTVERKCCVECPPCPAPPVAGPS VFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNST YRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMT KNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQE GNVFSCSVLHEALHSHYTQKSLSLSLG
>C Chain DIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQQKPGKAPKLLIYGATNLADGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
>D Chain DIQMTQSPSSLSASVGDRVTITCGASENIYGALNWYQQKPGKAPKLLIYGATNLADGVPS RFSGSGSGTDFTLTISSLQPEDFATYYCQNVLNTPLTFGQGTKVEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
Download FASTA FormatReferences:
- KEGG Drug: Ravulizumab [Link]
- Synonyms
- Ravulizumab
- ravulizumab-cwvz
- External IDs
- ALXN-1210
- ALXN1210
Pharmacology
- Indication
Ravulizumab is indicated for the treatment of adult and pediatric patients one month of age and older with paroxysmal nocturnal hemoglobinuria (PNH).4
It is also indicated for the treatment of adult and pediatric patients one month of age and older with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy (TMA). However, the FDA advises against the use of ravulizumab for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS).4
Ravulizumab is also indicated for treatment of adult patients with generalized myasthenia gravis (gMG) who are anti-acetylcholine receptor (AChR) antibody-positive.4,5
The European Commission approved ravulizumab for the treatment of paroxysmal nocturnal haemoglobinuria (PNH) in adults and children with a body weight of 10 kg or more with the following conditions: hemolysis with clinical symptoms indicative of high disease activity or clinically stable after having been treated with eculizumab for at least the past six months. Ravulizumab is also indicated for the treatment of hemolytic uremic syndrome (aHUS) in patients with a body weight of 10 kg or more who are either complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab.5
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- Contraindications & Blackbox Warnings
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- Pharmacodynamics
Ravulizumab is a potent long-acting complement inhibitor of C5, which is a key complement protein involved in inflammatory and thrombotic pathways.1 It has a long duration of action and fast onset of action. In a clinical study of adult and pediatric patients with paroxysmal nocturnal hemoglobinuria, completion inhibition of free C5 - determined as the serum concentration of less than 0.5 mcg/mL - was observed by the end of the first ravulizumab infusion: this effect was sustained throughout the entire 26-week treatment period. In patients with atypical hemolytic uremic syndrome, inhibition of C5 was observed in 93% of the patients in the study. C5 inhibition by ravulizumab is exposure-dependent.4
- Mechanism of action
Complement system activation plays an important role in innate and acquired immunity. Paroxysmal nocturnal hemoglobinuria (PNH) is a hematopoietic stem cell disorder characterized by hemolytic anemia, bone marrow failure, and thrombosis. It is caused by a genetic mutation, leading to complement-mediated hemolysis and deficiencies in glycosylphosphatidylinositol (GPI)-linked proteins such as those involved in fibrinolysis.2 Atypical hemolytic uraemic syndrome (aHUS) is a type of thrombotic microangiopathy also caused by complement dysregulation. It is associated with thrombocytopenia, microangiopathic hemolytic anemia, and end-organ damage.3 Myasthenia gravis, an autoimmune neuromuscular disease, also involves the immune system aberrantly attacking the muscles, causing progressive muscle damage.5
Ravulizumab inhibits the terminal complement pathway by binding to C5 with high affinity: this inhibits the cleavage of C5 to C5a, which is a pro-inflammatory and pro-thrombotic anaphylatoxin, and C5b, an initiating subunit of the terminal complement complex (C5b-9), which promotes cell lysis. Since the generation of C5b is blocked, the formation of C5b-9 is also inhibited by ravulizumab.1,4 Ravulizumab inhibits terminal complement-mediated intravascular hemolysis in patients with PNH and complement-mediated thrombotic microangiopathy (TMA) in patients with aHUS.4 By blocking the complement system, ravulizumab ameliorates the extent of inflammatory and immune responses that play a role in the pathophysiology of myasthenia gravis.5
Target Actions Organism AComplement C5 inhibitorHumans - Absorption
In children with paroxysmal nocturnal hemoglobinuria who are complement inhibitor-naïve, the mean Cmax was 733 mcg/mL following the loading dose and 1490 mcg/mL following the maintenance dose. In children who were previously treated with eculizumab, the mean Cmax was 885 mcg/mL following the loading dose and 1705 mcg/mL following the maintenance dose.4
In adults with paroxysmal nocturnal hemoglobinuria who are complement inhibitor-naïve, the mean Cmax was 771 mcg/mL following the loading dose and 1379 mcg/mL following the maintenance dose. In adults who were previously treated with eculizumab, the mean Cmax was 843 mcg/mL following the loading dose and 1386 mcg/mL following the maintenance dose.4
In children with atypical hemolytic uremic syndrome and a body weight of less than 20 kg, the mean Cmax was 656 mcg/mL following the loading dose and 1467 mcg/mL following the maintenance dose. In children with a body weight ranging from 20 to 40 kg, the mean Cmax was 600 mcg/mL following the loading dose and 1863 mcg/mL following the maintenance dose. In adults with a body weight greater than 40 kg, the mean Cmax was 754 mcg/mL following the loading dose and 1458 mcg/mL following the maintenance dose.4
Tmax is expected at the end of infusion (EOI) or soon after EOI. Therapeutic steady-state drug concentrations are reached after the first dose.5
- Volume of distribution
The mean (%CV) volume of distribution at steady state was 5.30 (17.9) L in patients with paroxysmal nocturnal hemoglobinuria and 5.22 (35.4) L in patients with atypical hemolytic uremic syndrome.4
- Protein binding
There is no information on the protein binding of ravulizumab.
- Metabolism
Ravulizumab is expected to be metabolized in the same manner as any endogenous immunoglobulin gamma monoclonal antibody: it undergoes degradation into small peptides and amino acids via catabolic pathways. Ravulizumab contains only natural occurring amino acids and has no known active metabolites.5
- Route of elimination
There is no information on the route of elimination of ravulizumab.
- Half-life
The mean (%CV) terminal elimination half-life of ravulizumab is 49.6 (18.3) days in patients with paroxysmal nocturnal hemoglobinuria and 51.8 (31.3) days in patients with atypical hemolytic uremic syndrome.4
- Clearance
The mean (%CV) clearance of ravulizumab is 0.08 (28.1) L/day in patients with paroxysmal nocturnal hemoglobinuria and 0.08 (53.3) L/day in patients with atypical hemolytic uremic syndrome.4
- Adverse Effects
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- Toxicity
There is no information on the LD50 value of ravulizumab.
No case of ravulizumab overdose has been reported to date. Patients who experience overdose should have immediate interruption of their infusion and be closely monitored.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 softwareAbatacept The risk or severity of adverse effects can be increased when Abatacept is combined with Ravulizumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Ravulizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Ravulizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Ravulizumab. Aducanumab The risk or severity of adverse effects can be increased when Ravulizumab is combined with Aducanumab. Aldesleukin The risk or severity of adverse effects can be increased when Aldesleukin is combined with Ravulizumab. Alefacept The risk or severity of adverse effects can be increased when Alefacept is combined with Ravulizumab. Alemtuzumab The risk or severity of adverse effects can be increased when Alemtuzumab is combined with Ravulizumab. Alirocumab The risk or severity of adverse effects can be increased when Alirocumab is combined with Ravulizumab. Allogeneic processed thymus tissue The therapeutic efficacy of Allogeneic processed thymus tissue can be decreased when used in combination with Ravulizumab. Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more - 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 Ultomiris Solution 300 mg / 3 mL Intravenous Alexion Pharma Gmbh 2023-04-19 Not applicable Canada Ultomiris Kit; Solution 245 mg/3.5mL Subcutaneous Alexion Pharmaceuticals Inc. 2023-04-01 Not applicable US Ultomiris Injection, solution, concentrate 300 mg Intravenous Alexion Europe Sas 2021-03-17 Not applicable EU Ultomiris Injection, solution, concentrate 300 mg/30mL Intravenous Alexion Pharmaceuticals Inc. 2018-12-21 Not applicable US Ultomiris Injection, solution 245 mg Subcutaneous Alexion Europe Sas 2023-07-22 Not applicable EU Ultomiris Injection, solution, concentrate 10 mg / mL Intravenous Alexion Pharma Gmbh Not applicable Not applicable Canada Ultomiris Injection, solution, concentrate 1100 mg/11mL Intravenous Alexion Pharmaceuticals Inc. 2018-12-21 Not applicable US Ultomiris Solution 1100 mg / 11 mL Intravenous Alexion Pharma Gmbh 2023-04-19 Not applicable Canada Ultomiris Injection, solution, concentrate 300 mg Intravenous Alexion Europe Sas 2021-02-11 Not applicable EU Ultomiris Injection, solution, concentrate 1100 mg Intravenous Alexion Europe Sas 2021-03-17 Not applicable EU
Categories
- ATC Codes
- L04AA43 — Ravulizumab
- Drug Categories
- Amino Acids, Peptides, and Proteins
- Antibodies
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- Antineoplastic and Immunomodulating Agents
- Blood Proteins
- Complement Inactivating Agents
- Complement Inactivator Proteins
- Globulins
- Immunoglobulins
- Immunologic Factors
- Immunoproteins
- Immunosuppressive Agents
- Immunotherapy
- Proteins
- Selective Immunosuppressants
- Serum Globulins
- Chemical TaxonomyProvided by Classyfire
- Description
- Not Available
- Kingdom
- Organic Compounds
- Super Class
- Organic Acids
- Class
- Carboxylic Acids and Derivatives
- Sub Class
- Amino Acids, Peptides, and Analogues
- Direct Parent
- Peptides
- Alternative Parents
- Not Available
- Substituents
- Not Available
- Molecular Framework
- Not Available
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- C3VX249T6L
- CAS number
- 1803171-55-2
References
- Synthesis Reference
Method for simultaneous quantification of alxn1210 and eculizumab in human serum or urine: WO20 8183449A1, Ryan Pelto, Meng Chen
- General References
- Ladwig PM, Willrich MAV: Ravulizumab: Characterization and quantitation of a new C5 inhibitor using isotype specific affinity purification and high-resolution mass spectrometry. J Mass Spectrom Adv Clin Lab. 2021 Aug 12;21:10-18. doi: 10.1016/j.jmsacl.2021.08.002. eCollection 2021 Aug. [Article]
- Stern RM, Connell NT: Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2019 Sep 10;10:2040620719874728. doi: 10.1177/2040620719874728. eCollection 2019. [Article]
- Syed YY: Ravulizumab: A Review in Atypical Haemolytic Uraemic Syndrome. Drugs. 2021 Apr;81(5):587-594. doi: 10.1007/s40265-021-01481-6. [Article]
- FDA Approved Drug Products: ULTOMIRIS (ravulizumab-cwvz) injection, for intravenous use [Link]
- EMA Summary of Product Characteristics: Ultomiris (ravulizumab) intravenous infusion [Link]
- European Medicines Agency Medicines: Ultomiris (ravulizumab) [Link]
- ClinicalTrials.gov: Ravulizumab and COVID-19 (NCT04570397) [Link]
- External Links
- 2107316
- Wikipedia
- Ravulizumab
- FDA label
- Download (1.29 MB)
Clinical Trials
- Clinical Trials
Phase Status Purpose Conditions Count 4 Completed Treatment Paroxysmal Nocturnal Haemoglobinuria (PNH) 1 4 Unknown Status Treatment Coronavirus Disease 2019 (COVID‑19) 1 3 Active Not Recruiting Treatment Acute Kidney Injury (AKI) / Coronavirus Disease 2019 (COVID‑19) / Thrombotic Microangiopathies 1 3 Active Not Recruiting Treatment Neuromyelitis Optica (NMO) / Neuromyelitis Optica Spectrum Disorders 1 3 Completed Treatment Atypical Hemolytic Uremic Syndrome (aHUS) 2 3 Completed Treatment Generalized Myasthenia Gravis 1 3 Completed Treatment Paroxysmal Nocturnal Haemoglobinuria (PNH) 5 3 Recruiting Treatment Cardiac Diseases / Cardiopulmonary Bypass / Chronic Kidney Disease (CKD) / CKD 1 3 Recruiting Treatment Generalized Myasthenia Gravis / GMG 1 3 Recruiting Treatment Paroxysmal Nocturnal Haemoglobinuria (PNH) 1
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 245 mg Injection, solution, concentrate Intravenous 10 mg / mL Injection, solution, concentrate Intravenous 1100 mg/11mL Injection, solution, concentrate Intravenous 1100 MG Injection, solution, concentrate Intravenous 300 MG Injection, solution, concentrate Intravenous 300 mg/3mL Injection, solution, concentrate Intravenous 300 mg/30mL Kit; solution Subcutaneous 245 mg/3.5mL Solution Intravenous 1100 mg / 11 mL Solution Intravenous 300 mg / 3 mL - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Liquid
- Experimental Properties
- Not Available
Targets

- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- 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
- Ladwig PM, Willrich MAV: Ravulizumab: Characterization and quantitation of a new C5 inhibitor using isotype specific affinity purification and high-resolution mass spectrometry. J Mass Spectrom Adv Clin Lab. 2021 Aug 12;21:10-18. doi: 10.1016/j.jmsacl.2021.08.002. eCollection 2021 Aug. [Article]
- Stern RM, Connell NT: Ravulizumab: a novel C5 inhibitor for the treatment of paroxysmal nocturnal hemoglobinuria. Ther Adv Hematol. 2019 Sep 10;10:2040620719874728. doi: 10.1177/2040620719874728. eCollection 2019. [Article]
- FDA Approved Drug Products: ULTOMIRIS (ravulizumab-cwvz) injection, for intravenous use [Link]
- Ravulizumab FDA Label [File]
Drug created at April 17, 2016 22:44 / Updated at November 29, 2022 09:06