Pralsetinib

Pralsetinib
Names
Trade namesGavreto
Other namesBLU-667
IUPAC name
  • N-[(1S)-1-[6-(4-fluoropyrazol-1-yl)pyridin-3-yl]ethyl]-1-methoxy-4-[4-methyl-6-[(5-methyl-1H-pyrazol-3-yl)amino]pyrimidin-2-yl]cyclohexane-1-carboxamide
Clinical data
Drug classTyrosine kinase inhibitor[1]
Main usesNon-small cell lung cancer (NSCLC), thyroid cancer[1]
Side effectsConstipation, high blood pressure, tiredness, muscle pain, low blood cells, liver problems, low calcium[1]
Routes of
use		By mouth
Typical dose400 mg OD[1]
External links
AHFS/Drugs.comMonograph
US NLMPralsetinib
MedlinePlusa620057
Legal
License data
Legal status
Chemical and physical data
FormulaC27H32FN9O2
Molar mass533.612 g·mol−1
3D model (JSmol)
SMILES
  • CC1=CC(=NN1)NC2=NC(=NC(=C2)C)C3CCC(CC3)(C(=O)NC(C)C4=CN=C(C=C4)N5C=C(C=N5)F)OC
InChI
  • InChI=1S/C27H32FN9O2/c1-16-11-22(33-23-12-17(2)35-36-23)34-25(31-16)19-7-9-27(39-4,10-8-19)26(38)32-18(3)20-5-6-24(29-13-20)37-15-21(28)14-30-37/h5-6,11-15,18-19H,7-10H2,1-4H3,(H,32,38)(H2,31,33,34,35,36)/t18-,19?,27?/m0/s1
  • Key:GBLBJPZSROAGMF-SIYOEGHHSA-N

Pralsetinib, sold under the brand name Gavreto, is a medication used to treat non-small cell lung cancer (NSCLC) and thyroid cancer.[1] It is used in advanced cases which are RET fusion-positive.[1] It is taken by mouth.[1]

Common side effects include constipation, high blood pressure, tiredness, muscle pain, low blood cells, liver problems, and low calcium.[1] Other side effects may include pneumonitis, bleeding, tumor lysis syndrome, and poor wound healing.[1] Use in pregnancy may harm the baby.[1] It is a tyrosine kinase inhibitor.[1]

Pralsetinib was approved for medical use in the United States in 2020.[1] In the United States it costs about 20,100 USD per month.[2] It is not approved for use in the United Kingdom as of 2021.[3]

Medical uses

Pralsetinib is indicated for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test.[4][5]

Dosage

It is generally taken at a dose of 400 mg once daily.[1]

History

Efficacy was investigated in a multicenter, open-label, multi-cohort clinical trial (ARROW, NCT03037385) with 220 participants aged 26-87 whose tumors had RET alterations.[4][5] Identification of RET gene alterations was prospectively determined in local laboratories using either next generation sequencing, fluorescence in situ hybridization, or other tests.[4] The main efficacy outcome measures were overall response rate (ORR) and response duration determined by a blinded independent review committee using RECIST 1.1.[4] The trial was conducted at sites in the United States, Europe and Asia.[5]

Efficacy for RET fusion-positive NSCLC was evaluated in 87 participants previously treated with platinum chemotherapy.[4] The ORR was 57% (95% CI: 46%, 68%); 80% of responding participants had responses lasting 6 months or longer.[4] Efficacy was also evaluated in 27 participants who never received systemic treatment.[4] The ORR for these participants was 70% (95% CI: 50%, 86%); 58% of responding participants had responses lasting 6 months or longer.[4]

The US Food and Drug Administration (FDA) granted the application for pralsetinib priority review, orphan drug, and breakthrough therapy designations[4]and granted approval of Gavreto to Blueprint Medicines.[4]

Society and culture

On 16 September 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Gavreto, intended for the treatment of people with rearranged during transfection (RET)-fusion positive non-small cell lung cancer (NSCLC).[6] The applicant for this medicinal product is Roche Registration GmbH.[6]

References

  1. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 "Gavreto- pralsetinib capsule". DailyMed. 9 September 2020. Archived from the original on 28 November 2020. Retrieved 24 September 2020.
  2. ↑ "Gavreto Prices, Coupons & Patient Assistance Programs". Drugs.com. Retrieved 29 October 2021.
  3. ↑ "Pralsetinib". SPS - Specialist Pharmacy Service. 4 July 2020. Archived from the original on 29 October 2021. Retrieved 29 October 2021.
  4. 1 2 3 4 5 6 7 8 9 10 "FDA approves pralsetinib for lung cancer with RET gene fusions". U.S. Food and Drug Administration (FDA). 4 September 2020. Archived from the original on 9 September 2020. Retrieved 8 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  5. 1 2 3 "Drug Trial Snapshot: Gavreto". U.S. Food and Drug Administration. 4 September 2020. Archived from the original on 25 October 2020. Retrieved 16 September 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  6. 1 2 "Gavreto: Pending EC decision". European Medicines Agency. 17 September 2021. Archived from the original on 17 September 2021. Retrieved 17 September 2021. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
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