Infigratinib
{{Short description|Medication}}
{{Use American English|date=May 2021}}
{{Use dmy dates|date=May 2021}}
{{Infobox drug
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| image = Infigratinib.png
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| tradename = Truseltiq
| Drugs.com = {{drugs.com|monograph|infigratinib}}
| MedlinePlus = a621041
| licence_EU =
| DailyMedID = Infigratinib
| licence_US =
| pregnancy_AU = D
| pregnancy_AU_comment = {{cite web | title=Updates to the Prescribing Medicines in Pregnancy database | website=Therapeutic Goods Administration (TGA) | date=12 May 2022 | url=https://www.tga.gov.au/resources/resource/guidance/updates-prescribing-medicines-pregnancy-database | access-date=13 May 2022 | archive-date=3 April 2022 | archive-url=https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database | url-status=live }}
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| routes_of_administration = By mouth
| class = Tyrosine kinase inhibitor
| ATCvet =
| ATC_prefix = L01
| ATC_suffix = EN03
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| legal_AU = S4
| legal_AU_comment = {{cite web | title=Truseltiq | website=Therapeutic Goods Administration (TGA) | date=22 November 2021 | url=https://www.tga.gov.au/apm-summary/truseltiq | access-date=28 December 2021}}
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| legal_CA = Rx-only
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| legal_US = Rx-only
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| CAS_number = 872511-34-7
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| PubChem = 53235510
| IUPHAR_ligand =
| DrugBank = DB11886
| ChemSpiderID = 26333103
| UNII = A4055ME1VK
| KEGG = D11589
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| PDB_ligand =
| synonyms = BGJ-398
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| C=26 | H=31 | Cl=2 | N=7 | O=3
| SMILES = CCN1CCN(c2ccc(Nc3cc(N(C)C(=O)Nc4c(Cl)c(OC)cc(OC)c4Cl)ncn3)cc2)CC1
| StdInChI = 1S/C26H31Cl2N7O3/c1-5-34-10-12-35(13-11-34)18-8-6-17(7-9-18)31-21-15-22(30-16-29-21)33(2)26(36)32-25-23(27)19(37-3)14-20(38-4)24(25)28/h6-9,14-16H,5,10-13H2,1-4H3,(H,32,36)(H,29,30,31)
| StdInChI_comment =
| StdInChIKey = QADPYRIHXKWUSV-UHFFFAOYSA-N
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Infigratinib is an kinase inhibitor in development for the treatment of achondroplasia and hypochondroplasia.{{Cite web |title=Infigratinib Research {{!}} FGFR3 & Achondroplasia {{!}} QED Tx |url=https://qedtx.com/our-research/ |access-date=2024-08-15 |website=qedtx.com}}
Infigratinib targets the fibroblast growth factor receptors FGFR1, FGFR2, and FGFR3.{{cite journal | vauthors = Botrus G, Raman P, Oliver T, Bekaii-Saab T | title = Infigratinib (BGJ398): an investigational agent for the treatment of FGFR-altered intrahepatic cholangiocarcinoma | journal = Expert Opinion on Investigational Drugs | volume = 30 | issue = 4 | pages = 309–316 | date = April 2021 | pmid = 33307867 | doi = 10.1080/13543784.2021.1864320 | s2cid = 229177726 | url = }}
Infigratinib was originally approved at a higher dose for medical use in the United States in May 2021 for cholangiocarcinoma, but is no longer marketed for that indication due to difficulties commercializing in the indication.{{cite web | title=Drug Trials Snapshots: Truseltiq | website=U.S. Food and Drug Administration (FDA) | date=28 May 2021 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-truseltiq | access-date=1 August 2023 | archive-date=28 July 2023 | archive-url=https://web.archive.org/web/20230728202614/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-truseltiq | url-status=dead }} {{PD-notice}}{{cite press release | title=BridgeBio Pharma's Affiliate QED Therapeutics and Partner Helsinn Group Announce FDA Approval of Truseltiq (infigratinib) for Patients with Cholangiocarcinoma | publisher=BridgeBio Pharma | via=GlobeNewswire | date=28 May 2021 | url=https://www.globenewswire.com/news-release/2021/05/28/2238443/0/en/BridgeBio-Pharma-s-Affiliate-QED-Therapeutics-and-Partner-Helsinn-Group-Announce-FDA-Approval-of-TRUSELTIQ-infigratinib-for-Patients-with-Cholangiocarcinoma.html | access-date=28 May 2021}}{{cite report | title=Advancing Health Through Innovation: New Drug Therapy Approvals 2021 | website=U.S. Food and Drug Administration (FDA) | date=13 May 2022 | url=https://www.fda.gov/media/155227/download | format=PDF | access-date=22 January 2023 | archive-date=6 December 2022 | archive-url=https://web.archive.org/web/20221206210020/https://www.fda.gov/media/155227/download | url-status=dead }} {{PD-notice}}{{Cite journal |last=Research |first=Center for Drug Evaluation and |date=2024-08-09 |title=WITHDRAWN: FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma |url=https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma |archive-url=https://web.archive.org/web/20240520215941/https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma |url-status=dead |archive-date=20 May 2024 |journal=FDA |language=en}}
Medical uses
Infigratinib is currently in clinical trials for the treatment of children with achondroplasia. Infigratinib is now in a Phase 3 clinical trial.{{Cite web |last=Condon |first=Holly |date=2023-12-13 |title=BridgeBio Announces First Child Dosed in PROPEL 3, its Phase 3 Clinical Trial for Infigratinib in Children with Achondroplasia |url=https://bridgebio.com/news/bridgebio-announces-first-child-dosed-with-infigratinib-in-propel-3-its-phase-3-clinical-trial-in-children-with-achondroplasia/ |access-date=2024-08-15 |website=BridgeBio |language=en-US}}
Infigratinib was originally developed at a higher dose for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (bile duct cancer) with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test.
History
The US Food and Drug Administration (FDA) approved infigratinib based on evidence from one clinical trial (NCT02150967) of 108 participants with bile duct cancer (cholangiocarcinoma). The CBGJ398X2204 trial was a multicenter open-label single-arm trial that enrolled 108 participants with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement as determined by local or central testing. The trials were conducted at 18 sites in the United States, Europe, and Asia. The trial enrolled adult participants with bile duct cancer who had been treated previously with chemotherapy for their advanced cancer and whose tumors had a certain type of abnormality in the FGFR2 gene. Participants received infigratinib once daily by mouth for 21 consecutive days followed by 7 days off therapy. This 28-day cycle was administered until disease progression or the side effects became too toxic. The trial measured the percentage of participants who achieved partial or complete shrinkage of their cancer and how long that shrinkage lasted (duration of response or DoR).
Infigratinib has since been developed at a lower dose (0.25 mg/kg) for children with achondroplasia, a condition caused by variants in the FGFR3 gene. Preliminary Phase 2 results showed that children treated with infigratinib showed a mean change from baseline in annualized height velocity of +2.51 cm/yr at 12 months, with no serious adverse events.
Society and culture
= Legal status =
Infigratinib was designated an orphan drug by the FDA{{cite web | title=Infigratinib Orphan Drug Designations and Approvals | website=U.S. Food and Drug Administration (FDA) | date=11 September 2019 | url=https://www.accessdata.fda.gov/scripts/opdlisting/oopd/listResult.cfm | access-date=30 May 2021 | archive-date=28 October 2022 | archive-url=https://web.archive.org/web/20221028174419/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/index.cfm | url-status=dead }} and the European Medicines Agency in 2021.{{cite web | title=EU/3/21/2475 | website=European Medicines Agency | date=13 June 2022 | url=https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-21-2475 | access-date=1 August 2023 | archive-date=30 May 2023 | archive-url=https://web.archive.org/web/20230530122920/https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-21-2475 | url-status=live }} It was approved for medical use under the FDA's accelerated approval program in May 2021.{{cite web | title=FDA grants accelerated approval to infigratinib for metastatic cholang | website=U.S. Food and Drug Administration | date=28 May 2021 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma | access-date=1 August 2023 | archive-date=2 August 2023 | archive-url=https://web.archive.org/web/20230802054006/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-infigratinib-metastatic-cholangiocarcinoma | url-status=dead }} {{PD-notice}} Infigratinib has since been withdrawn from commercialization due to the sponsor's difficulties distributing the drug and enrolling a confirmatory clinical trial.
References
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External links
- {{ClinicalTrialsGov|NCT02150967|A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma}}
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