Infigratinib

Infigratinib
Clinical data
Trade namesTruseltiq
Other namesBGJ-398
AHFS/Drugs.comMonograph
MedlinePlusa621041
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classTyrosine kinase inhibitor
ATC code
Legal status
Legal status
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC26H31Cl2N7O3
Molar mass560.48 g·mol−1
3D model (JSmol)
  • CCN1CCN(c2ccc(Nc3cc(N(C)C(=O)Nc4c(Cl)c(OC)cc(OC)c4Cl)ncn3)cc2)CC1
  • InChI=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)
  • Key:QADPYRIHXKWUSV-UHFFFAOYSA-N

Infigratinib is an kinase inhibitor in development for the treatment of achondroplasia and hypochondroplasia.[1][4][5]

Infigratinib targets the fibroblast growth factor receptors FGFR1, FGFR2, and FGFR3.[4][6]

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.[4][7][8][9][10][11]

Medical uses

Infigratinib is currently in clinical trials for the treatment of children with achondroplasia. Infigratinib is now in a Phase 3 clinical trial.[12]

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.[4][7]

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).[7] 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.[8] The trials were conducted at 18 sites in the United States, Europe, and Asia.[7] 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.[7] Participants received infigratinib once daily by mouth for 21 consecutive days followed by 7 days off therapy.[7] This 28-day cycle was administered until disease progression or the side effects became too toxic.[7] 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).[7]

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

Infigratinib was designated an orphan drug by the FDA[13] and the European Medicines Agency in 2021.[14] It was approved for medical use under the FDA's accelerated approval program in May 2021.[7][8] Infigratinib has since been withdrawn from commercialization due to the sponsor's difficulties distributing the drug and enrolling a confirmatory clinical trial.[11]

References

  1. ^ a b c "Truseltiq". Therapeutic Goods Administration (TGA). 22 November 2021. Retrieved 28 December 2021.
  2. ^ "Updates to the Prescribing Medicines in Pregnancy database". Therapeutic Goods Administration (TGA). 12 May 2022. Archived from the original on 3 April 2022. Retrieved 13 May 2022.
  3. ^ "Summary Basis of Decision (SBD) for Truseltiq". Health Canada. 23 October 2014. Archived from the original on 29 May 2022. Retrieved 29 May 2022.
  4. ^ a b c d e "Truseltiq- infigratinib capsule". DailyMed. Archived from the original on 10 June 2021. Retrieved 10 June 2021.
  5. ^ "Infigratinib Research | FGFR3 & Achondroplasia | QED Tx". qedtx.com. Retrieved 15 August 2024.
  6. ^ Botrus G, Raman P, Oliver T, Bekaii-Saab T (April 2021). "Infigratinib (BGJ398): an investigational agent for the treatment of FGFR-altered intrahepatic cholangiocarcinoma". Expert Opinion on Investigational Drugs. 30 (4): 309–316. doi:10.1080/13543784.2021.1864320. PMID 33307867. S2CID 229177726.
  7. ^ a b c d e f g h i "Drug Trials Snapshots: Truseltiq". U.S. Food and Drug Administration (FDA). 28 May 2021. Archived from the original on 28 July 2023. Retrieved 1 August 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  8. ^ a b c "FDA grants accelerated approval to infigratinib for metastatic cholang". U.S. Food and Drug Administration. 28 May 2021. Archived from the original on 2 August 2023. Retrieved 1 August 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  9. ^ "BridgeBio Pharma's Affiliate QED Therapeutics and Partner Helsinn Group Announce FDA Approval of Truseltiq (infigratinib) for Patients with Cholangiocarcinoma" (Press release). BridgeBio Pharma. 28 May 2021. Retrieved 28 May 2021 – via GlobeNewswire.
  10. ^ Advancing Health Through Innovation: New Drug Therapy Approvals 2021 (PDF). U.S. Food and Drug Administration (FDA) (Report). 13 May 2022. Archived from the original on 6 December 2022. Retrieved 22 January 2023. Public Domain This article incorporates text from this source, which is in the public domain.
  11. ^ a b Research, Center for Drug Evaluation and (9 August 2024). "WITHDRAWN: FDA grants accelerated approval to infigratinib for metastatic cholangiocarcinoma". FDA.
  12. ^ Condon, Holly (13 December 2023). "BridgeBio Announces First Child Dosed in PROPEL 3, its Phase 3 Clinical Trial for Infigratinib in Children with Achondroplasia". BridgeBio. Retrieved 15 August 2024.
  13. ^ "Infigratinib Orphan Drug Designations and Approvals". U.S. Food and Drug Administration (FDA). 11 September 2019. Archived from the original on 28 October 2022. Retrieved 30 May 2021.
  14. ^ "EU/3/21/2475". European Medicines Agency. 13 June 2022. Archived from the original on 30 May 2023. Retrieved 1 August 2023.
  • Clinical trial number NCT02150967 for "A Phase II, Single Arm Study of BGJ398 in Patients With Advanced Cholangiocarcinoma" at ClinicalTrials.gov