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Iptacopan

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Iptacopan
Clinical data
Trade namesFabhalta
Other namesLNP023
AHFS/Drugs.comFabhalta
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classComplement factor B inhibitor
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
Chemical and physical data
FormulaC25H30N2O4
Molar mass422.525 g·mol−1
3D model (JSmol)
  • 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, sold under the brand name Fabhalta, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria (PNH).[3] It is a complement factor B inhibitor that was developed by Novartis.[3] It is taken by mouth.[3]

Iptacopan was approved by the US Food and Drug Administration (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023.[5][6] The FDA considers it to be a first-in-class medication.[7]

Medical uses

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Iptacopan is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria.[3][8]

Mechanism of action

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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.[9]

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.[9]

Side effects

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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.[3]

Society and culture

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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 hemoglobinuria (PNH).[4][10] The applicant for this medicinal product is Novartis Europharm Limited.[4] Iptacopan was approved for medical use in the European Union in May 2024.[4]

In August 2024, the US FDA granted accelerated approval to Fabhalta (iptacopan) for reducing proteinuria in adults with primary IgA nephropathy (IgAN).[11]

Research

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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.[12][13]

Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related macular degeneration and some types of glomerulopathies.[14]

References

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  1. ^ a b "Fabhalta (iptacopan)". Therapeutic Goods Administration (TGA). 19 August 2024. Retrieved 12 October 2024.
  2. ^ "Fabhalta (Novartis Pharmaceuticals Australia Pty Ltd)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
  3. ^ 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.
  4. ^ a b c d "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.
  5. ^ "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.
  6. ^ "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.
  7. ^ 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.
  8. ^ "Fabhalta (iptacopan) capsules approval letter" (PDF). U.S. Food and Drug Administration. Archived from the original (PDF) on 10 December 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  9. ^ a b "FABHALTA (iptacopan) capsules, for oral use" (PDF). Highlights of Prescribing Information. Novartis Pharmaceuticals Corporation.
  10. ^ "Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 March 2024". European Medicines Agency (Press release). 22 March 2024. Retrieved 13 June 2024.
  11. ^ Rani A (8 August 2024). "US FDA approves Novartis' Fabhalta in IgAN treatment". Pharmaceutical Technology. Retrieved 8 August 2024.
  12. ^ 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.
  13. ^ "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). Archived from the original on 12 December 2023. Retrieved 6 September 2023.
  14. ^ 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.
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  • 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
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