Avapritinib

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Avapritinib
Names
PronunciationA va PRI ti nib
Trade namesAyvakit, Ayvakyt
Other namesBLU-285, BLU285
  • (1S)-1-(4-fluorophenyl)-1-(2-{4-[6-(1-methyl-1H-pyrazol4-yl)pyrrolo[2,1-f][1,2,4]triazin-4-yl]piperazin-1-yl}pyrimidin5-yl)ethan-1-amine
Clinical data
Drug classTyrosine kinase inhibitor[1]
Main usesSystemic mastocytosis, gastrointestinal stromal tumor (GIST)[2]
Side effectsNausea, tiredness, low red blood cells, swelling, high bilirubin, diarrhea, forgetfulness[1]
Routes of
use		By mouth
External links
AHFS/Drugs.comMonograph
MedlinePlusa620013
Legal
License data
Legal status
Chemical and physical data
FormulaC26H27FN10
Molar mass498.570 g·mol−1
3D model (JSmol)
  • CC(C1=CC=C(C=C1)F)(C2=CN=C(N=C2)N3CCN(CC3)C4=NC=NN5C4=CC(=C5)C6=CN(N=C6)C)N
  • InChI=1S/C26H27FN10/c1-26(28,20-3-5-22(27)6-4-20)21-13-29-25(30-14-21)36-9-7-35(8-10-36)24-23-11-18(16-37(23)33-17-31-24)19-12-32-34(2)15-19/h3-6,11-17H,7-10,28H2,1-2H3/t26-/m0/s1
  • Key:DWYRIWUZIJHQKQ-SANMLTNESA-N

Avapritinib, sold under the brand name Ayvakit, is a medication used to treat systemic mastocytosis and gastrointestinal stromal tumor (GIST).[2] In GIST it is used for cases with a platelet-derived growth factor receptor A (PDGFRA) exon 18 mutation.[2] It is taken by mouth.[2]

Common side effects nausea, tiredness, low red blood cells, swelling, high bilirubin, diarrhea, and forgetfulness.[1] Other side effects may include pleural effusion and intracranial bleeding.[2][1] Use in pregnancy may harm the baby.[2] It is a tyrosine kinase inhibitor that blocks the activity of PDGFRA.[1]

Avapritinib was approved for medical use in the United States and Europe in 2020.[2][1] In the United Kingdom a month costs the NHS about £26,700 as of 2021.[3] This amount in the United States costs about 34,200 USD.[4]

Medical uses

Avapritinib is indicated for the treatment of adults with unresectable or metastatic gastrointestinal stromal tumors (GIST) harboring the platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.[2][1]

Avapritinib is also indicated for the treatment of adults with advanced systemic mastocytosis, aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia (MCL).[5]

Dosage

It is taken at a dose of 200 to 300 mg per day.[2]

History

The U.S. Food and Drug Administration (FDA) approved avapritinib in January 2020.[6][7][8] The application for avapritinib was granted fast track designation, breakthrough therapy designation, and orphan drug designation.[6] The FDA granted approval of Ayvakit to Blueprint Medicines Corporation.[6]

Avapritinib was approved based on the results from the Phase I NAVIGATOR[9][10] clinical trial involving 43 subjects with GIST harboring a PDGFRA exon 18 mutation, including 38 subjects with PDGFRA D842V mutation.[6] Subjects received avapritinib 300 mg or 400 mg orally once daily until disease progression or they experienced unacceptable toxicity.[6] The recommended dose was determined to be 300 mg once daily.[6] The trial measured how many subjects experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate).[6] For subjects harboring a PDGFRA exon 18 mutation, the overall response rate was 84%, with 7% having a complete response and 77% having a partial response.[6] For the subgroup of subjects with PDGFRA D842V mutations, the overall response rate was 89%, with 8% having a complete response and 82% having a partial response.[6] While the median duration of response was not reached, 61% of the responding subjects with exon 18 mutations had a response lasting six months or longer (31% of subjects with an ongoing response were followed for less than six months).[6]

The FDA approved avapritinib based on evidence from one clinical trial (NCT02508532) of 204 subjects with GIST.[7] The trial was conducted at 17 sites in the United States, Europe and Asia.[7]

Avapritinib showed a median PFS of 4.2 months compared to 5.6 months for regorafenib. The difference in median PFS between the avapritinib and regorafenib groups was not statistically significant. The overall response rate was 17 percent for the avapritinib group and 7 percent for the regorafenib group. The VOYAGER trial evaluated the efficacy and safety of avapritinib (N=240) versus regorafenib (N=236) in patients with third- or fourth-line GIST.[11]

Avapritinib was approved for medical use in the European Union in September 2020.[1]

Ayvakit was granted approval for advanced systemic mastocytosis by the FDA on June 16th 2021. [12]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 1.8 "Ayvakyt EPAR". European Medicines Agency (EMA). 20 July 2020. Archived from the original on 1 November 2020. Retrieved 29 September 2020. Text was copied from this source which is © European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 2.9 "Ayvakit- avapritinib tablet, film coated". DailyMed. 21 January 2020. Archived from the original on 27 September 2020. Retrieved 29 September 2020.
  3. ↑ BNF 81: March-September 2021. BMJ Group and the Pharmaceutical Press. 2021. p. 1013. ISBN 978-0857114105.
  4. ↑ "Avapritinib Prices, Coupons & Savings Tips - GoodRx". GoodRx. Retrieved 16 January 2022.
  5. ↑ "FDA approves avapritinib for advanced systemic mastocytosis". U.S. Food and Drug Administration (FDA). 16 June 2021. Archived from the original on 16 June 2021. Retrieved 16 June 2021. Public Domain This article incorporates text from this source, which is in the public domain.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 6.7 6.8 6.9 "FDA approves the first targeted therapy to treat a rare mutation in patients with gastrointestinal stromal tumors". U.S. Food and Drug Administration (FDA) (Press release). 9 January 2020. Archived from the original on 11 January 2020. Retrieved 9 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  7. ↑ 7.0 7.1 7.2 "Drug Trial Snapshot: Ayvakit". U.S. Food and Drug Administration (FDA). 9 January 2020. Archived from the original on 24 January 2020. Retrieved 24 January 2020. Public Domain This article incorporates text from this source, which is in the public domain.
  8. ↑ "Drug Approval Package: Ayvakit". U.S. Food and Drug Administration (FDA). 13 February 2020. Archived from the original on 13 April 2021. Retrieved 16 June 2021.
  9. ↑ "Blueprint Medicines Announces FDA Approval of Ayvakit (avapritinib) for the Treatment of Adults with Unresectable or Metastatic PDGFRA Exon 18 Mutant Gastrointestinal Stromal Tumor". Blueprint Medicines Corporation (Press release). 9 January 2020. Archived from the original on 11 January 2020. Retrieved 9 January 2020.
  10. ↑ "Blueprint Medicines Announces Updated NAVIGATOR Trial Results in Patients with Advanced Gastrointestinal Stromal Tumors Supporting Development of Avapritinib Across All Lines of Therapy". Blueprint Medicines Corporation (Press release). 15 November 2018. Archived from the original on 10 January 2020. Retrieved 9 January 2020.
  11. ↑ "Blueprint Medicines Announces Top-line Results from Phase 3 VOYAGER Trial of Avapritinib versus Regorafenib in Patients with Advanced Gastrointestinal Stromal Tumor". Blueprint Medicines Corporation (Press release). 28 April 2020. Archived from the original on 24 June 2021. Retrieved 22 June 2021.
  12. ↑ Research, Center for Drug Evaluation and (16 June 2021). "FDA approves avapritinib for advanced systemic mastocytosis". FDA. Archived from the original on 16 June 2021. Retrieved 22 June 2021.

External links

Identifiers:
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