Iptacopan

Summary

Iptacopan (CHEMBL4594448) is an approved small-molecule complement factor B inhibitor (ATC L04AJ08) targeting CFB; indicated across 11 conditions including iga glomerulonephritis and atypical hemolytic-uremic syndrome.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: L04AJ08
• Targets: 1 (CFB)
• Indications: 11 conditions
• Clinical trials: 33
• Chemistry: 422.5 Da · C25H30N2O4

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL4594448
Name	Iptacopan
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	90467622
ChEBI	CHEBI:229652
ATC	L04AJ08
Molecular formula	C25H30N2O4
Molecular weight	422.5
InChIKey	RENRQMCACQEWFC-UGKGYDQZSA-N

SMILES: CCO[C@H]1CCN([C@@H](C1)C2=CC=C(C=C2)C(=O)O)CC3=C(C=C(C4=C3C=CN4)C)OC

IUPAC name: 4-[(2S,4S)-4-ethoxy-1-[(5-methoxy-7-methyl-1H-indol-4-yl)methyl]piperidin-2-yl]benzoic acid

ChEBI definition: A member of the class of indoles that is 1H-indole substituted by [(2S,4S)-2-(4-carboxyphenyl)-4-ethoxypiperidin-1-yl]methyl, methoxy, and methyl groups at positions 4, 5, and 6, respectively. It is a potent inhibitor of complement factor B (IC50 = 10nM) with potential immunomodulatory activity.

Pharmacological roles (ChEBI): complement factor B inhibitor, immunomodulator.

Also known as: Iptacopan, LNP-023, Lnp023, LNP023, NVP-LNP023, COD41, IPTACOPAN

Parent form; salt/anhydrous children: CHEMBL4643495, CHEMBL5095401

Patent coverage: 155 distinct patent families (397 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 313 (79%) of the total. Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.

Targets

Targets

Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).

Gene	Target	Action	pAffinity	Cancer dependency	UniProt
CFB	complement factor B	Inhibition	7.92	1.6%	P00751

Broader ChEMBL bioactivity targets: 3 (assay-derived). Sample: Alpha-1A adrenergic receptor, Complement factor B, Complement factor B.

Bioactivity

ChEMBL activities: 8 potent at pChembl ≥ 5 of 8 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
CFB	11	IC50	0.01	nM	CHEMBL_ACT_26710064
CFB	8.1	Kd	7.9	nM	CHEMBL_ACT_20647451
CFB	7.92	IC50	12	nM	CHEMBL_ACT_20647480
ADRA1A	7.92	IC50	12	nM	CHEMBL_ACT_29055319
P04186	6.96	IC50	110	nM	CHEMBL_ACT_20647494
CFB	6.89	IC50	130	nM	CHEMBL_ACT_20647487
CFB	6.4	IC50	400	nM	CHEMBL_ACT_20647568
CFB	5.96	IC50	1100	nM	CHEMBL_ACT_26952283

Target pathways

Aggregated over 1 target gene(s): CFB.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Alternative complement activation	1	CFB
Activation of C3 and C5	1	CFB
Regulation of Complement cascade	1	CFB

Dominant GO biological processes

GO term	Targets
proteolysis	1
complement activation	1
complement activation, alternative pathway	1
response to bacterium	1
immune system process	1
innate immune response	1

Indications & clinical

Indications

11 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).

Indication	Trial phase	MONDO	EFO
IgA glomerulonephritis	3	MONDO:0005342	EFO:0004194
atypical hemolytic-uremic syndrome	3	MONDO:0016244	MONDO:0016244
membranoproliferative glomerulonephritis	3	MONDO:0002461	MONDO:0018904
hemoglobinuria	3	MONDO:0003656	MONDO:0100244
membranous glomerulonephritis	2	MONDO:0005376	EFO:0004254
glomerulonephritis	2	MONDO:0002462	MONDO:0002462
age-related macular degeneration	2	MONDO:0005150	EFO:0001365
lupus nephritis	2	MONDO:0005556	EFO:0005761
liver disorder	1	MONDO:0005154	EFO:0001421
kidney disorder	1	MONDO:0005240	HP:0000077

1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 33.

Phase distribution

Phase	Trials
PHASE3	14
PHASE2	11
Not specified	7
PHASE1	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT03955445	PHASE3	RECRUITING	Long-term Efficacy, Safety and Tolerability of Iptacopan in C3G or IC-MPGN
NCT04557462	PHASE3	RECRUITING	A Rollover Extension Program (REP) to Evaluate the Long-term Safety and Tolerability of Open Label Iptacopan/LNP023 in Participants With Primary IgA Nephropathy
NCT04747613	PHASE3	ACTIVE_NOT_RECRUITING	Long-term Safety and Tolerability of Iptacopan in Patients With Paroxysmal Nocturnal Hemoglobinuria
NCT04817618	PHASE3	RECRUITING	Study of Efficacy and Safety of Iptacopan in Patients With C3 Glomerulopathy.
NCT05755386	PHASE3	RECRUITING	Study of Efficacy and Safety of Iptacopan in Participants With IC-MPGN
NCT05935215	PHASE3	RECRUITING	Efficacy and Safety of Switching From Anti-C5 Antibody Treatment to Iptacopan Treatment in Study Participants With Atypical Hemolytic Uremic Syndrome (aHUS)
NCT06517758	PHASE3	RECRUITING	A Phase III Study to Investigate Efficacy, Safety and Tolerability of Iptacopan Compared With Placebo in Participants Aged 18 to 85 Years With gMG.
NCT06934967	PHASE3	RECRUITING	Study to Assess the Pharmacokinetics, Safety, and Tolerability of Iptacopan in Pediatric PNH Patients
NCT06994845	PHASE3	RECRUITING	Study to Assess the Efficacy, Pharmacokinetics, Safety and Tolerability of Iptacopan in Pediatric Patients With Primary IgAN
NCT04558918	PHASE3	COMPLETED	Study of Efficacy and Safety of Twice Daily Oral LNP023 in Adult PNH Patients With Residual Anemia Despite Anti-C5 Antibody Treatment
NCT04578834	PHASE3	COMPLETED	Study of Efficacy and Safety of LNP023 in Primary IgA Nephropathy Patients
NCT04820530	PHASE3	COMPLETED	Study of Efficacy and Safety of Twice Daily Oral Iptacopan (LNP023) in Adult PNH Patients Who Are Naive to Complement Inhibitor Therapy
NCT04889430	PHASE3	COMPLETED	Efficacy and Safety of Iptacopan (LNP023) in Adult Patients With Atypical Hemolytic Uremic Syndrome Naive to Complement Inhibitor Therapy
NCT05630001	PHASE3	COMPLETED	Single Arm, Open Label Trial With Iptacopan Treatment for 24 Weeks, in Patients on Stable Regimen of Anti-C5 Who Switch to Iptacopan.
NCT05230537	PHASE2	ACTIVE_NOT_RECRUITING	A Masked, Placebo-controlled Study to Assess Iptacopan in Age-related Macular Degeneration
NCT05268289	PHASE2	RECRUITING	Study of Efficacy and Safety of LNP023 in Participants With Active Lupus Nephritis Class III-IV, +/- V
NCT06388941	PHASE2	ACTIVE_NOT_RECRUITING	Iptacopan in Patients With ANCA Associated Vasculitis
NCT06797518	PHASE2	RECRUITING	Study to Evaluate the Impact of Iptacopan on Top of SOC on Biopsy Changes in Kidneys of Adult Patients With IgAN
NCT02534909	PHASE2	COMPLETED	Proof of Concept Study to Assess the Efficacy, Safety and Pharmacokinetics of LFG316 in Patients With Paroxysmal Nocturnal Hemoglobinuria
NCT03373461	PHASE2	COMPLETED	Study of Safety and Efficacy of LNP023 in Patients With Kidney Disease Caused by Inflammation
NCT03439839	PHASE2	COMPLETED	Study of Safety, Efficacy, Tolerability, Pharmacokinetics and Pharmacodynamics of LNP023 in in Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH)
NCT03832114	PHASE2	COMPLETED	Study on Efficacy and Safety of LNP023 in C3 Glomerulopathy Patients Transplanted and Not Transplanted
NCT03896152	PHASE2	COMPLETED	Efficacy, Safety, Pharmacokinetics and Pharmacodynamics Study, Assessing Multiple LNP023 Doses in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria
NCT04154787	PHASE2	TERMINATED	Efficacy and Safety of LNP023 Compared With Rituximab in Subjects With Idiopathic Membranous Nephropathy
NCT05086744	PHASE2	TERMINATED	Basket Study to Assess Efficacy, Safety and PK of Iptacopan (LNP023) in Autoimmune Benign Hematological Disorders
NCT05078580	PHASE1	COMPLETED	Pharmacokinetic (PK) and Safety Study of Iptacopan (LNP023) in Participants With Mild, Moderate, and Severe Hepatic Impairment Compared to Matched Control Healthy Participants With Normal Hepatic Function.
NCT05222412	Not specified	AVAILABLE	Managed Access Programs for LNP023, Iptacopan
NCT06847607	Not specified	NOT_YET_RECRUITING	A Multicenter Prospective Study of Iptacopan in the Treatment of Refractory/Relapsed Autoimmune Hemolytic Anemia (AIHA)
NCT06903234	Not specified	ACTIVE_NOT_RECRUITING	Post-authorization Safety Study of Iptacopan in Adult Patients With Paroxysmal Nocturnal Hemoglobinuria (PNH) Using Data From the IPIG PNH Registry
NCT06931691	Not specified	RECRUITING	A Multi-center, Ambispective Cohort Study to Evaluate the Impact of Iptacopan for Adult Patients With PNH in China
NCT06952426	Not specified	RECRUITING	A Mobile App-Based Study to Evaluate Disease Burden and Treatment Patterns in Immunoglobulin A Nephropathy (IgAN) in the US
NCT07331259	Not specified	NOT_YET_RECRUITING	CHART-C3G/CLNP023B12011
NCT07347990	Not specified	NOT_YET_RECRUITING	Safety and Efficacy of Iptacopan in Patients With High-Risk Transplantation-Associated Thrombotic Microangiopathy

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No PharmGKB pharmacogenomic data curated for this drug.

Related molecules

Related molecules

No competitor molecules sharing a primary target (ChEMBL phase ≥2 or PubChem drug-class).