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Avapritinib
Clinical data
Pronunciation	A va PRI ti nib
Trade names	Ayvakit, Ayvakyt
Other names	BLU-285, BLU285
AHFS/Drugs.com	Monograph
MedlinePlus	a620013
License data	US DailyMed: Avapritinib;
Routes of; administration	By mouth
Drug class	Antineoplastic agent
ATC code	L01EX18 (WHO) ;
Legal status
Legal status	US: ℞-only; EU: Rx-only;
Identifiers
	IUPAC name (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;
CAS Number	1703793-34-3;
PubChem CID	118023034;
DrugBank	DB15233;
ChemSpider	58828673;
UNII	513P80B4YJ;
KEGG	D11279;
ChEMBL	ChEMBL4204794;
CompTox Dashboard (EPA)	DTXSID301027935 ;
Chemical and physical data
Formula	C26H27FN10
Molar mass	498.570 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES Cn1cc(-c2cc3c(N4CCN(c5ncc(C(C)(N)c6ccc(F)cc6)cn5)CC4)ncnn3c2)cn1;
	InChI 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 among others, is a medication used for the treatment of advanced systemic mastocytosis and indolent systemic mastocytosis. It is also used for the treatment of tumors due to one specific rare mutation: it is specifically intended for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) that harbor a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation.^[1]^[4] Avapritinib is a kinase inhibitor.^[4]

Common side effects include edema (swelling), nausea, fatigue/asthenia (abnormal physical weakness or lack of energy), cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation (secretion of tears), abdominal pain, constipation, rash and dizziness.^[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.^[1]^[2]

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] It is also indicated for the treatment of adults with indolent systemic mastocytosis.

History

The U.S. Food and Drug Administration (FDA) approved avapritinib in January 2020.^[4]^[6]^[7] The application for avapritinib was granted fast track designation, breakthrough therapy designation, and orphan drug designation.^[4] The FDA granted approval of Ayvakit to Blueprint Medicines Corporation.^[4]

Avapritinib was approved based on the results from the Phase I NAVIGATOR^[8]^[9] clinical trial involving 43 subjects with GIST harboring a PDGFRA exon 18 mutation, including 38 subjects with PDGFRA D842V mutation.^[4] Subjects received avapritinib 300 mg or 400 mg orally once daily until disease progression or they experienced unacceptable toxicity.^[4] The recommended dose was determined to be 300 mg once daily.^[4] The trial measured how many subjects experienced complete or partial shrinkage (by a certain amount) of their tumors during treatment (overall response rate).^[4] 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.^[4] 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.^[4] 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).^[4]

The FDA approved avapritinib based on evidence from one clinical trial (NCT02508532) of 204 subjects with GIST.^[6] The trial was conducted at 17 sites in the United States, Europe and Asia.^[6]

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.^[10]

Avapritinib was approved for medical use in the European Union in September 2020.^[2]

Ayvakit was granted approval for advanced systemic mastocytosis by the FDA in June 2021.^[11]

In May 2023, the FDA granted approval for the use of avapritinib for indolent systemic mastocytosis.^[12]

References

^ ^a ^b ^c "Ayvakit- avapritinib tablet, film coated". DailyMed. 21 January 2020. Archived from the original on 27 September 2020. Retrieved 29 September 2020.
^ ^a ^b ^c "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 copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
^ "Ayvakyt Product information". Union Register of medicinal products. Archived from the original on 5 March 2023. Retrieved 3 March 2023.
^ ^a ^b ^c ^d ^e ^f ^g ^h ⁱ ^j ^k ^l ^m "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. This article incorporates text from this source, which is in the public domain.
^ "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. This article incorporates text from this source, which is in the public domain.
^ ^a ^b ^c "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. This article incorporates text from this source, which is in the public domain.
^ "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.
^ "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.
^ "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.
^ "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 16 June 2021.
^ "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.
^ "FDA Approves Avapritinib for the Treatment of Indolent Systemic Mastocytosis". Pharmacy Times. 22 May 2023. Retrieved 2 October 2024.

External links

"Avapritinib". NCI Dictionary of Cancer Terms. National Cancer Institute.
"Avapritinib". National Cancer Institute. 28 January 2020.
Clinical trial number NCT02508532 for "(NAVIGATOR) Study of BLU-285 in Patients With Gastrointestinal Stromal Tumors (GIST) and Other Relapsed and Refractory Solid Tumors" at ClinicalTrials.gov
Clinical trial number NCT02561988 for "(EXPLORER) Study of BLU-285 in Patients With Advanced Systemic Mastocytosis (AdvSM) and Relapsed or Refractory Myeloid Malignancies" at ClinicalTrials.gov
Clinical trial number NCT03580655 for "(PATHFINDER) Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients With Advanced Systemic Mastocytosis" at ClinicalTrials.gov