Rozanolixizumab
Explore a selection of our essential drug information below, or:
Identification
- Summary
Rozanolixizumab is a humanized monoclonal antibody targeting the human neonatal Fc receptor (FcRn) used to treat generalized myasthenia gravis.
- Brand Names
- Rystiggo
- Generic Name
- Rozanolixizumab
- DrugBank Accession Number
- DB14919
- Background
Rozanolixizumab is a humanized high-affinity anti-human neonatal Fc receptor (FcRn) monoclonal antibody (IgG4P) targeting the immunoglobulin G (IgG). Rozonolixizumab itself is an IgG4P, an inactive isotype, to reduce the likelihood of unwanted chain exchange.1 It is investigated for use in autoimmune and alloimmune diseases with pathologic IgG, particularly generalized myasthenia gravis.2 Generalized myasthenia gravis is characterized by the formation of IgG antibodies against the nicotinic acetylcholine receptor (AChR) or muscle-specific tyrosine kinase (MuSK).3,4,5 Approximately 80% of myasthenia gravis patients tested positive for the AChR autoantibodies, and 40% of these AChR-negative or seronegative patients were found to have MuSK autoantibodies.7
AChR is vital for signal transduction in the neuromuscular junctions (NMJ) by generating muscle end plate potentials to propagate action potential.4 Therefore, the presence of AChR-antibodies can interfere with the ACh-mediated downstream signaling, thus reducing the likelihood of end plate potentials reaching the threshold needed to trigger an action potential.4 As a result, the main clinical manifestation of myasthenia gravis is easily fatigable or persistent muscle weakness.4 On the other hand, MuSK activation can trigger the clustering of AChR at the NMJ, guide the innervation of motor neurons toward AChR-dense areas, and anchor acetylcholinesterase.3,6 Therefore, autoantibodies against MuSK can also affect the signal propagation at the NMJ.
Rozanolixizumab-noli is available under the brand name RYSTIGGO and was developed by UCB.9 It was granted orphan drug designation by the FDA in 2019, by the European Medicines Agency (EMA) in April 2020, and by the Japanese Pharmaceuticals and Medical Devices Agency (PMDA) in November 2020.9 In June 2023, Rozanolixizumab-noli was approved by the FDA under Priority Review for the treatment of adult patients with generalized myasthenia gravis who are positive for the anti-acetylcholine receptor (AchR) or anti-muscle-specific tyrosine kinase (MuSK) antibody.9 This is due to the efficacy demonstrated in the pivotal Phase 3 MycarinG study (NCT03971422).9 Rozanolixizumab was also approved by the European Commission on January 5, 2024.10
- Type
- Biotech
- Groups
- Approved, Investigational
- Biologic Classification
- Protein Based Therapies
Monoclonal antibody (mAb) - Protein Chemical Formula
- Not Available
- Protein Average Weight
- 148000.0 Da
- Sequences
- Not Available
- Synonyms
- Rozanolixizumab
- UCB7665
Pharmacology
- Indication
Rozanolixizumab-noli is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive.8,10
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 Generalized myasthenia gravis •••••••••••• ••••• •••••••••••••••••••• •••••••• •••••• •••••• •••••••• ••••••••• •••••••••••••••••• •••••••• •••••••• •••••••• ••••••••• Treatment of Generalized myasthenia gravis •••••••••••• ••••• •••••••••••••••••••• •••••••• •••••• •••••• •••••••• ••••••••• •••••••••••••••••• •••••••• •••••••• •••••••• ••••••••• - Associated Therapies
- 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 pharmacological effect of rozanolixizumab-noli was assessed by measuring the decrease in serum IgG levels and AChR and MuSK autoantibody levels. In patients testing positive for AChR and MuSK autoantibodies who were treated with RYSTIGGO, there was a reduction in total IgG levels relative to baseline. Decreases in AChR autoantibody and MuSK autoantibody levels followed a similar pattern.8
- Mechanism of action
Rozanolixizumab-noli is a humanized IgG4 monoclonal antibody that binds to the neonatal Fc receptor (FcRn), resulting in the reduction of circulating IgG.8
Target Actions Organism AIgG receptor FcRn large subunit p51 antibodyHumans - Absorption
Rozanolixizumab-noli exhibited nonlinear pharmacokinetics. Rozanolixizumab-noli exposure increased in a greater than dose-proportional manner over a dose range from 1 mg/kg to 20 mg/kg (two times the maximum recommended dose) following subcutaneous administration.8
Following subcutaneous administration of rozanolixizumab-noli, peak plasma levels were achieved after approximately 2 days in healthy subjects.8
- Volume of distribution
The apparent volume of distribution of rozanolixizumab-noli is 6.6 L.8
- Protein binding
Not Available
- Metabolism
Rozanolixizumab-noli is expected to be degraded by proteolytic enzymes into small peptides and amino acids.8
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
The apparent clearance for the rozanolixizumab-noli is 0.89 L/day.8
- 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
There are limited data on rozanolixizumab-noli use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Following the administration of rozanolixizumab-noli to pregnant monkeys at doses greater than those used clinically, increases in embryonic death, reduced body weight, and impaired immune function were observed in the absence of maternal toxicity.8
Subcutaneous administration of rozanolixizumab-noli (0 or 150 mg/kg) every 3 days for 26 weeks to sexually mature cynomolgus monkeys resulted in no adverse effects on sperm parameters (count, motility, or morphology) or estrus cyclicity. The dose tested in monkeys is 30 times the maximum recommended human dose of approximately 10 mg/kg, on a mg/kg/week basis.8
- 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 Rozanolixizumab. Abciximab The risk or severity of adverse effects can be increased when Abciximab is combined with Rozanolixizumab. Adalimumab The risk or severity of adverse effects can be increased when Adalimumab is combined with Rozanolixizumab. Adenovirus type 7 vaccine live The risk or severity of infection can be increased when Adenovirus type 7 vaccine live is combined with Rozanolixizumab. Aducanumab The risk or severity of adverse effects can be increased when Aducanumab is combined with Rozanolixizumab. - 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 Rystiggo Injection, solution 140 mg/ml Subcutaneous Ucb Pharma S.A. 2024-07-10 Not applicable EU Rystiggo Injection, solution 140 mg/1mL Subcutaneous Ucb Inc 2024-06-14 Not applicable US Rystiggo Injection, solution 140 mg/1mL Subcutaneous Ucb Inc 2024-06-14 Not applicable US Rystiggo Injection, solution 140 mg/1mL Subcutaneous Ucb Inc 2023-06-26 Not applicable US Rystiggo Injection, solution 140 mg/1mL Subcutaneous Ucb Inc 2024-06-14 Not applicable US
Categories
- ATC Codes
- L04AG16 — Rozanolixizumab
- Drug Categories
- 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
- Not Available
Chemical Identifiers
- UNII
- P7186074QC
- CAS number
- 1584645-37-3
References
- General References
- Kiessling P, Lledo-Garcia R, Watanabe S, Langdon G, Tran D, Bari M, Christodoulou L, Jones E, Price G, Smith B, Brennan F, White I, Jolles S: The FcRn inhibitor rozanolixizumab reduces human serum IgG concentration: A randomized phase 1 study. Sci Transl Med. 2017 Nov 1;9(414):eaan1208. doi: 10.1126/scitranslmed.aan1208. [Article]
- Smith B, Kiessling A, Lledo-Garcia R, Dixon KL, Christodoulou L, Catley MC, Atherfold P, D'Hooghe LE, Finney H, Greenslade K, Hailu H, Kevorkian L, Lightwood D, Meier C, Munro R, Qureshi O, Sarkar K, Shaw SP, Tewari R, Turner A, Tyson K, West S, Shaw S, Brennan FR: Generation and characterization of a high affinity anti-human FcRn antibody, rozanolixizumab, and the effects of different molecular formats on the reduction of plasma IgG concentration. MAbs. 2018 Oct;10(7):1111-1130. doi: 10.1080/19420862.2018.1505464. Epub 2018 Sep 12. [Article]
- Rivner MH, Pasnoor M, Dimachkie MM, Barohn RJ, Mei L: Muscle-Specific Tyrosine Kinase and Myasthenia Gravis Owing to Other Antibodies. Neurol Clin. 2018 May;36(2):293-310. doi: 10.1016/j.ncl.2018.01.004. [Article]
- Gable KL, Guptill JT: Antagonism of the Neonatal Fc Receptor as an Emerging Treatment for Myasthenia Gravis. Front Immunol. 2020 Jan 10;10:3052. doi: 10.3389/fimmu.2019.03052. eCollection 2019. [Article]
- Rodolico C, Bonanno C, Toscano A, Vita G: MuSK-Associated Myasthenia Gravis: Clinical Features and Management. Front Neurol. 2020 Jul 23;11:660. doi: 10.3389/fneur.2020.00660. eCollection 2020. [Article]
- Cao M, Koneczny I, Vincent A: Myasthenia Gravis With Antibodies Against Muscle Specific Kinase: An Update on Clinical Features, Pathophysiology and Treatment. Front Mol Neurosci. 2020 Sep 2;13:159. doi: 10.3389/fnmol.2020.00159. eCollection 2020. [Article]
- Huijbers MG, Zhang W, Klooster R, Niks EH, Friese MB, Straasheijm KR, Thijssen PE, Vrolijk H, Plomp JJ, Vogels P, Losen M, Van der Maarel SM, Burden SJ, Verschuuren JJ: MuSK IgG4 autoantibodies cause myasthenia gravis by inhibiting binding between MuSK and Lrp4. Proc Natl Acad Sci U S A. 2013 Dec 17;110(51):20783-8. doi: 10.1073/pnas.1313944110. Epub 2013 Dec 2. [Article]
- FDA Approved Drug Products: RYSTIGGO® (rozanolixizumab-noli) injection, for subcutaneous use [Link]
- UCB announces U.S. FDA approval of RYSTIGGO® (rozanolixizumab-noli) for the treatment of adults with generalized myasthenia gravis [Link]
- EMA Approved Drug Products: Rystiggo (rozanolixizumab) Subcutaneous Injection [Link]
- External Links
- 2642274
- Wikipedia
- Rozanolixizumab
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample dataNot Available No Longer Available Not Available Chronic Inflammatory Demyelinating Polyradiculoneuropathy 1 somestatus stop reason just information to hide 3 Completed Treatment Generalized Myasthenia Gravis 4 somestatus stop reason just information to hide 3 Not Yet Recruiting Treatment Generalized Myasthenia Gravis 1 somestatus stop reason just information to hide 3 Recruiting Treatment Myelin Oligodendrocyte Glycoprotein Antibody-associated Disease (MOG-AD) 1 somestatus stop reason just information to hide 3 Terminated Treatment Primary Immune Thrombocytopenia (ITP) 3 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
Form Route Strength Injection, solution Subcutaneous 140 mg/ml Injection, solution Subcutaneous 140 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
- Cell surface receptor that transfers passive humoral immunity from the mother to the newborn. Binds to the Fc region of monomeric immunoglobulin gamma and mediates its selective uptake from milk (PubMed:10933786, PubMed:7964511). IgG in the milk is bound at the apical surface of the intestinal epithelium. The resultant FcRn-IgG complexes are transcytosed across the intestinal epithelium and IgG is released from FcRn into blood or tissue fluids. Throughout life, contributes to effective humoral immunity by recycling IgG and extending its half-life in the circulation. Mechanistically, monomeric IgG binding to FcRn in acidic endosomes of endothelial and hematopoietic cells recycles IgG to the cell surface where it is released into the circulation (PubMed:10998088). In addition of IgG, regulates homeostasis of the other most abundant circulating protein albumin/ALB (PubMed:24469444, PubMed:28330995)
- Specific Function
- beta-2-microglobulin binding
- Gene Name
- FCGRT
- Uniprot ID
- P55899
- Uniprot Name
- IgG receptor FcRn large subunit p51
- Molecular Weight
- 39742.99 Da
References
- FDA Approved Drug Products: RYSTIGGO® (rozanolixizumab-noli) injection, for subcutaneous use [Link]
Drug created at May 20, 2019 14:35 / Updated at July 27, 2024 07:22