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Wikipedia

Iptacopan

April 12, 2024

Iptacopan , sold under the brand name Fabhalta, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria.[1] It is a complement factor B inhibitor that was developed by Novartis.[1] It is taken by mouth.[1]

Iptacopan
Clinical data
Trade namesFabhalta
Other namesLNP023
AHFS/Drugs.comFabhalta
License data
Routes of
administration		By mouth
Drug classComplement factor B inhibitor
ATC code
Legal status
Legal status
Identifiers
CAS Number
  • 1644670-37-0
PubChem CID
  • 90467622
DrugBank
  • DB16200
ChemSpider
  • 75533872
UNII
  • 8E05T07Z6W
KEGG
  • D12251
  • D12252
ChEMBL
  • ChEMBL4594448
PDB ligand
  • JGQ (PDBe, RCSB PDB)
Chemical and physical data
FormulaC25H30N2O4
Molar mass422.525 g·mol−1
3D model (JSmol)
  • Interactive image
  • O=C(O)C1=CC=C([C@H]2N(CC3=C(OC)C=C(C)C4=C3C=CN4)CC[C@H](OCC)C2)C=C1
  • InChI=1S/C25H30N2O4/c1-4-31-19-10-12-27(22(14-19)17-5-7-18(8-6-17)25(28)29)15-21-20-9-11-26-24(20)16(2)13-23(21)30-3/h5-9,11,13,19,22,26H,4,10,12,14-15H2,1-3H3,(H,28,29)/t19-,22-/m0/s1
  • Key:RENRQMCACQEWFC-UGKGYDQZSA-N

Iptacopan was approved by the US Food and Drug Administration (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023.[2][3] The FDA considers it to be a first-in-class medication.[4]

Medical uses edit

Iptacopan is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria.[1][5]

Mechanism of action edit

Iptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3, generation of downstream effectors, and the amplification of the terminal pathway.[6]

In PNH, intravascular hemolysis (IVH) is mediated by the downstream membrane attack complex (MAC), while extravascular hemolysis (EVH) is facilitated by C3b opsonization. Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated EVH and terminal complement mediated IVH.[7]

Side effects edit

The FDA label for iptacopan contains a black box warning for the risk of serious and life-threatening infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B.[1]

Society and culture edit

Legal status edit

In March 2024, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Fabhalta, intended for the treatment of paroxysmal nocturnal haemoglobinuria (PNH).[8] The applicant for this medicinal product is Novartis Europharm Limited.[8]

Research edit

In a clinical study with twelve participants, iptacopan as a single drug led to the normalization of hemolytic markers in most patients, and no serious adverse events occurred during the 12-week study.[9][10]

Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related macular degeneration and some types of glomerulopathies.[11]

References edit

  1. ^ a b c d e f "Fabhalta- iptacopan capsule". DailyMed. 5 December 2023. from the original on 10 December 2023. Retrieved 10 December 2023.
  2. ^ "Novartis receives FDA approval for Fabhalta (iptacopan), offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH". Novartis (Press release). from the original on 12 December 2023. Retrieved 6 December 2023.
  3. ^ "Novel Drug Approvals for 2023". U.S. Food and Drug Administration (FDA). 6 December 2023. from the original on 21 January 2023. Retrieved 10 December 2023.
  4. ^ New Drug Therapy Approvals 2023 (PDF). U.S. Food and Drug Administration (FDA) (Report). January 2024. from the original on 10 January 2024. Retrieved 9 January 2024.
  5. ^ https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/218276Orig1s000ltr.pdf 10 December 2023 at the Wayback Machine   This article incorporates text from this source, which is in the public domain.
  6. ^ https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf
  7. ^ https://www.novartis.com/us-en/sites/novartis_us/files/fabhalta.pdf
  8. ^ a b "Fabhalta EPAR". European Medicines Agency (EMA). 21 March 2024. Retrieved 23 March 2024. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  9. ^ Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, et al. (August 2022). "Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria: a 2-cohort open-label proof-of-concept study". Blood Advances. 6 (15): 4450–4460. doi:10.1182/bloodadvances.2022006960. PMC 9636331. PMID 35561315.
  10. ^ "Novartis Phase III APPOINT-PNH trial shows investigational oral monotherapy iptacopan improves hemoglobin to near-normal levels, leading to transfusion independence in all treatment-naïve PNH patients". Novartis (Press release). from the original on 12 December 2023. Retrieved 6 September 2023.
  11. ^ Schubart A, Anderson K, Mainolfi N, Sellner H, Ehara T, Adams CM, et al. (April 2019). "Small-molecule factor B inhibitor for the treatment of complement-mediated diseases". Proceedings of the National Academy of Sciences of the United States of America. 116 (16): 7926–7931. Bibcode:2019PNAS..116.7926S. doi:10.1073/pnas.1820892116. PMC 6475383. PMID 30926668.

External links edit

  • Clinical trial number NCT04558918 for "Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment (APPLY-PNH)" at ClinicalTrials.gov
  • Clinical trial number NCT04820530 for "Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy (APPOINT-PNH)" at ClinicalTrials.gov

April 12, 2024
iptacopan, sold, under, brand, name, fabhalta, medication, used, treatment, paroxysmal, nocturnal, hemoglobinuria, complement, factor, inhibitor, that, developed, novartis, taken, mouth, clinical, datatrade, namesfabhaltaother, nameslnp023ahfs, drugs, comfabha. Iptacopan sold under the brand name Fabhalta is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria 1 It is a complement factor B inhibitor that was developed by Novartis 1 It is taken by mouth 1 IptacopanClinical dataTrade namesFabhaltaOther namesLNP023AHFS Drugs comFabhaltaLicense dataUS DailyMed IptacopanRoutes ofadministrationBy mouthDrug classComplement factor B inhibitorATC codeL04AJ08 WHO Legal statusLegal statusUS only 1 IdentifiersCAS Number1644670 37 0PubChem CID90467622DrugBankDB16200ChemSpider75533872UNII8E05T07Z6WKEGGD12251D12252ChEMBLChEMBL4594448PDB ligandJGQ PDBe RCSB PDB Chemical and physical dataFormulaC 25H 30N 2O 4Molar mass422 525 g mol 13D model JSmol Interactive imageSMILES O C O C1 CC C C H 2N CC3 C OC C C C C4 C3C CN4 CC C H OCC C2 C C1InChI InChI 1S C25H30N2O4 c1 4 31 19 10 12 27 22 14 19 17 5 7 18 8 6 17 25 28 29 15 21 20 9 11 26 24 20 16 2 13 23 21 30 3 h5 9 11 13 19 22 26H 4 10 12 14 15H2 1 3H3 H 28 29 t19 22 m0 s1Key RENRQMCACQEWFC UGKGYDQZSA NIptacopan was approved by the US Food and Drug Administration FDA for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023 2 3 The FDA considers it to be a first in class medication 4 Contents 1 Medical uses 2 Mechanism of action 3 Side effects 4 Society and culture 4 1 Legal status 5 Research 6 References 7 External linksMedical uses editIptacopan is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria 1 5 Mechanism of action editIptacopan binds to Factor B of the alternative complement pathway and regulates the cleavage of C3 generation of downstream effectors and the amplification of the terminal pathway 6 In PNH intravascular hemolysis IVH is mediated by the downstream membrane attack complex MAC while extravascular hemolysis EVH is facilitated by C3b opsonization Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b mediated EVH and terminal complement mediated IVH 7 Side effects editThe FDA label for iptacopan contains a black box warning for the risk of serious and life threatening infections caused by encapsulated bacteria including Streptococcus pneumoniae Neisseria meningitidis and Haemophilus influenzae type B 1 Society and culture editLegal status edit In March 2024 the Committee for Medicinal Products for Human Use CHMP of the European Medicines Agency EMA adopted a positive opinion recommending the granting of a marketing authorization for the medicinal product Fabhalta intended for the treatment of paroxysmal nocturnal haemoglobinuria PNH 8 The applicant for this medicinal product is Novartis Europharm Limited 8 Research editIn a clinical study with twelve participants iptacopan as a single drug led to the normalization of hemolytic markers in most patients and no serious adverse events occurred during the 12 week study 9 10 Iptacopan is also investigated as a drug in other complement mediated diseases like age related macular degeneration and some types of glomerulopathies 11 References edit a b c d e f Fabhalta iptacopan capsule DailyMed 5 December 2023 Archived from the original on 10 December 2023 Retrieved 10 December 2023 Novartis receives FDA approval for Fabhalta iptacopan offering superior hemoglobin improvement in the absence of transfusions as the first oral monotherapy for adults with PNH Novartis Press release Archived from the original on 12 December 2023 Retrieved 6 December 2023 Novel Drug Approvals for 2023 U S Food and Drug Administration FDA 6 December 2023 Archived from the original on 21 January 2023 Retrieved 10 December 2023 New Drug Therapy Approvals 2023 PDF U S Food and Drug Administration FDA Report January 2024 Archived from the original on 10 January 2024 Retrieved 9 January 2024 https www accessdata fda gov drugsatfda docs appletter 2023 218276Orig1s000ltr pdf Archived 10 December 2023 at the Wayback Machine nbsp This article incorporates text from this source which is in the public domain https www novartis com us en sites novartis us files fabhalta pdf https www novartis com us en sites novartis us files fabhalta pdf a b Fabhalta EPAR European Medicines Agency EMA 21 March 2024 Retrieved 23 March 2024 Text was copied from this source which is copyright European Medicines Agency Reproduction is authorized provided the source is acknowledged Jang JH Wong L Ko BS Yoon SS Li K Baltcheva I et al August 2022 Iptacopan monotherapy in patients with paroxysmal nocturnal hemoglobinuria a 2 cohort open label proof of concept study Blood Advances 6 15 4450 4460 doi 10 1182 bloodadvances 2022006960 PMC 9636331 PMID 35561315 Novartis Phase III APPOINT PNH trial shows investigational oral monotherapy iptacopan improves hemoglobin to near normal levels leading to transfusion independence in all treatment naive PNH patients Novartis Press release Archived from the original on 12 December 2023 Retrieved 6 September 2023 Schubart A Anderson K Mainolfi N Sellner H Ehara T Adams CM et al April 2019 Small molecule factor B inhibitor for the treatment of complement mediated diseases Proceedings of the National Academy of Sciences of the United States of America 116 16 7926 7931 Bibcode 2019PNAS 116 7926S doi 10 1073 pnas 1820892116 PMC 6475383 PMID 30926668 External links editClinical trial number NCT04558918 for Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti C5 Antibody Treatment APPLY PNH at ClinicalTrials gov Clinical trial number NCT04820530 for Study of Efficacy and Safety of Twice Daily Oral Iptacopan LNP023 in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy APPOINT PNH at ClinicalTrials gov Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Iptacopan amp oldid 1215234557, wikipedia, wiki, book, books, library,

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