Iptacopan

Iptacopan
Clinical data
Trade names	Fabhalta
Other names	LNP023
AHFS/Drugs.com	Template:Drugs.com
License data	US DailyMed: Iptacopan;
Pregnancy; category	AU: B1; ;
Routes of; administration	By mouth
Drug class	Complement factor B inhibitor
ATC code	L04AJ08 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); CA: ℞-only; US: ℞-only; EU: Rx-only;
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);
E number	{{#property:P628}}
CompTox Dashboard (EPA)	{{#property:P3117}};
ECHA InfoCard	{{#property:P2566}}
Chemical and physical data
Formula	C25H30N2O4
Molar mass	422.525 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES 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 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;

Created

2025-05-29 21:12

Contributors

WikiTeq Adm and Dermwiki

Article status

Unassigned

Clinical

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Differential

Histology

Features

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Differential

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Imaging

Diagnostic criteria

Management

Treatment

Monitoring

Counseling

Other considerations

Iptacopan, sold under the brand name Fabhalta, is a medication used for the treatment of paroxysmal nocturnal hemoglobinuria and proteinuria.^[5] It is a complement factor B inhibitor that was developed by Novartis.^[5] It is taken by mouth.^[5]

Iptacopan was approved for medical use in the United States in December 2023,^[5]^[7] and in the European Union in May 2024.^[6] The US Food and Drug Administration considers it to be a first-in-class medication.^[8]

Medical uses

Iptacopan is indicated for the treatment of adults with paroxysmal nocturnal hemoglobinuria;^[5]^[9] and to reduce proteinuria in adults with primary immunoglobulin A nephropathy at risk of rapid disease progression, generally a urine protein-to-creatinine ratio ≥1.5 g/g;^[5] for the treatment of adults with complement 3 glomerulopathy, to reduce proteinuria.^[5]

Complement 3 glomerulopathy is a rare disease that causes inflammation and damage to the kidney glomeruli, which are responsible for filtering blood and producing urine.^[10]

Mechanism of action

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.^[5]

In paroxysmal nocturnal hemoglobinuria, intravascular hemolysis is mediated by the downstream membrane attack complex, while extravascular hemolysis is facilitated by C3b opsonization.^[5] Iptacopan acts proximally in the alternative pathway of the complement cascade to control both C3b-mediated extravascular hemolysis and terminal complement mediated intravascular hemolysis.^[5]

Side effects

The US Food and Drug Administration label for iptacopan contains a boxed warning for the risk of serious and life-threatening infections caused by encapsulated bacteria, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae type B.^[5]

Society and culture

Legal status

Iptacopan was approved by the US Food and Drug Administration (FDA) for the treatment of adults with paroxysmal nocturnal hemoglobinuria in December 2023.^[11]

In March 2024, the Committee for Medicinal Products for Human Use 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.^[6]^[12] The applicant for this medicinal product is Novartis Europharm Limited.^[6] Iptacopan was authorized for medical use in the European Union in May 2024.^[6]

In August 2024, the US FDA granted accelerated approval to iptacopan for reducing proteinuria in adults with primary IgA nephropathy.^[13]

In March 2025, the US FDA approved iptacopan for the treatment of adults with complement 3 glomerulopathy to reduce proteinuria.^[10]

Research

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.^[14]^[15]

Iptacopan is also investigated as a drug in other complement-mediated diseases, like age-related macular degeneration and some types of glomerulopathies.^[16]

References

↑ ^1.0 ^1.1 "Fabhalta (iptacopan)". Therapeutic Goods Administration (TGA). 19 August 2024. Retrieved 12 October 2024.
↑ "Fabhalta (Novartis Pharmaceuticals Australia Pty Ltd)". Therapeutic Goods Administration (TGA). 13 September 2024. Retrieved 15 September 2024.
↑ "Register of Innovative Drugs". Health Canada. 13 January 2025. Retrieved 15 January 2025.
↑ "Notice: Multiple additions to the Prescription Drug List (PDL) [2025-02-26]". Health Canada. 26 February 2025. Retrieved 3 March 2025.
↑ ^5.00 ^5.01 ^5.02 ^5.03 ^5.04 ^5.05 ^5.06 ^5.07 ^5.08 ^5.09 ^5.10 ^5.11 "Fabhalta- iptacopan capsule". DailyMed. 5 December 2023. Archived from the original on 10 December 2023. Retrieved 10 December 2023.
↑ ^6.0 ^6.1 ^6.2 ^6.3 ^6.4 "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.
↑ "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.
↑ "Fabhalta (iptacopan) capsules approval letter" (PDF). U.S. Food and Drug Administration. Archived from the original (PDF) on 10 December 2023. This article incorporates text from this source, which is in the public domain.
↑ ^10.0 ^10.1 "FDA Roundup: March 21, 2025". U.S. Food and Drug Administration. 21 March 2025. Archived from the original on 20 April 2025. Retrieved 22 March 2025. This article incorporates text from this source, which is in the public domain.
↑ "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.
↑ "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.
↑ Rani A (8 August 2024). "US FDA approves Novartis' Fabhalta in IgAN treatment". Pharmaceutical Technology. Retrieved 8 August 2024.
↑ 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-naïve 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

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

Template:Immunosuppressants Template:Complement system

[Fabhalta_APMDS-1] 1.0 ^1.1 "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] "Register of Innovative Drugs". Health Canada. 13 January 2025. Retrieved 15 January 2025.

[4] "Notice: Multiple additions to the Prescription Drug List (PDL) [2025-02-26]". Health Canada. 26 February 2025. Retrieved 3 March 2025.

[Fabhalta_FDA_label-5] 5.00 ^5.01 ^5.02 ^5.03 ^5.04 ^5.05 ^5.06 ^5.07 ^5.08 ^5.09 ^5.10 ^5.11 "Fabhalta- iptacopan capsule". DailyMed. 5 December 2023. Archived from the original on 10 December 2023. Retrieved 10 December 2023.

[Fabhalta_EPAR-6] 6.0 ^6.1 ^6.2 ^6.3 ^6.4 "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.

[7] "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.

[8] 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.

[9] "Fabhalta (iptacopan) capsules approval letter" (PDF). U.S. Food and Drug Administration. Archived from the original (PDF) on 10 December 2023. This article incorporates text from this source, which is in the public domain.

[FDA_PR_20250321-10] 10.0 ^10.1 "FDA Roundup: March 21, 2025". U.S. Food and Drug Administration. 21 March 2025. Archived from the original on 20 April 2025. Retrieved 22 March 2025. This article incorporates text from this source, which is in the public domain.

[11] "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.

[12] "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.

[13] Rani A (8 August 2024). "US FDA approves Novartis' Fabhalta in IgAN treatment". Pharmaceutical Technology. Retrieved 8 August 2024.

[blood_adv-14] 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.

[15] "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.

[16] 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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