Pexidartinib

Pexidartinib, sold under the brand name Turalio, is a kinase inhibitor drug for the treatment of adults with symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery. Pexidartinib blocks the activity of the colony-stimulating factor-1 receptor (CSF-1R). [1][2][3][4]

Pexidartinib
Clinical data
Trade namesTuralio
Other namesPLX-3397
AHFS/Drugs.comMonograph
MedlinePlusa619050
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Identifiers
IUPAC name
  • 5-[(5-Chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)methyl]-N-{[6-(trifluoromethyl)-3-pyridinyl]methyl}-2-pyridinamine
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC20H15ClF3N5
Molar mass417.82 g·mol−1
3D model (JSmol)
SMILES
  • ClC=1C=C2C(=NC1)NC=C2CC=2C=CC(=NC2)NCC=2C=NC(=CC2)C(F)(F)F
InChI
  • InChI=1S/C20H15ClF3N5/c21-15-6-16-14(10-28-19(16)29-11-15)5-12-2-4-18(26-7-12)27-9-13-1-3-17(25-8-13)20(22,23)24/h1-4,6-8,10-11H,5,9H2,(H,26,27)(H,28,29)
  • Key:JGWRKYUXBBNENE-UHFFFAOYSA-N

Common side effects are increased lactate dehydrogenase (proteins that helps produce energy in the body), increased aspartate aminotransferase (enzymes that are mostly in the liver but also in muscles), loss of hair color, increased alanine aminotransferase (enzymes that are primarily in the liver and kidney) and increased cholesterol.[1] Additional side effects include neutropenia (low level of white blood cells that help the immune system defend against disease and infection), increased alkaline phosphatase (enzymes that are mostly in the cells of bone and the liver), decreased lymphocytes (white blood cells that help the immune system defend against disease and infection), eye edema (swelling around the eyes), decreased hemoglobin (protein in red blood cells that carry oxygen), rash, dysgeusia (altered sense of taste) and decreased phosphate (electrolytes that help with energy).[1] The US prescribing information for pexidartinib includes a boxed warning about the risk of serious and potentially fatal liver injury.[1][2]

In August 2019, it was approved by U.S. FDA for treatment of giant-cell tumor of the tendon sheath (GC-TS).[1][5][6] Pexidartinib is available in the US only through the Turalio Risk Evaluation and Mitigation Strategy (REMS) Program.[1] The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication.[7]

History

The approval of pexidartinib was based on the results of a multi-center international clinical trial of 120 subjects, 59 of whom received placebo.[1] The primary efficacy endpoint was the overall response rate (ORR) analyzed after 25 weeks of treatment.[1] The clinical trial demonstrated a statistically significant improvement in ORR in subjects who received pexidartinib, with an ORR of 38%, compared to no responses in subjects who received placebo.[1] The complete response rate was 15% and the partial response rate was 23%.[1] A total of 22 out of 23 responders who had been followed for a minimum of six months following the initial response maintained their response for six or more months, and a total of 13 out of 13 responders who had been followed for a minimum of 12 months following the initial response maintained their response for 12 or more months.[1]

The U.S. Food and Drug Administration (FDA) granted the application for pexidartinib breakthrough therapy designation, orphan drug designation, and priority review designation.[1] The FDA granted the approval of Turalio to Daiichi Sankyo.[1]

References
  1. "FDA approves first therapy for rare joint tumor". FDA (Press release). 2 August 2019. Retrieved 17 August 2019. This article incorporates text from this source, which is in the public domain.
  2. "Turalio- pexidartinib capsule". DailyMed. 7 August 2019. Retrieved 19 March 2020.
  3. "Pexidartinib Hydrochloride Monograph for Professionals". Drugs.com. 19 August 2019. Retrieved 19 March 2020.
  4. "Microglial Magic: Drug Wipes Them Out, New Set Appears". Alzforum. 18 April 2014. Retrieved 19 March 2020.
  5. "Drug Trials Snapshots: Turalio". U.S. Food and Drug Administration (FDA). 2 August 2019. Retrieved 17 March 2020.
  6. "Drug Approval Package: Turalio". U.S. Food and Drug Administration (FDA). 22 July 2019. Retrieved 17 March 2020.
  7. "New Drug Therapy Approvals 2019". U.S. Food and Drug Administration. 31 December 2019. Retrieved 15 September 2020.

Further reading
  • "Pexidartinib". Drug Information Portal. U.S. National Library of Medicine.
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