pralsetinib
{{Short description|Chemical compound}}
{{Use American English|date=September 2020}}
{{Use dmy dates|date=September 2020}}
{{Infobox drug
| image = Pralsetinib.svg
| width = 300
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| caption =
| pronounce =
| tradename = Gavreto
| Drugs.com = {{drugs.com|monograph|pralsetinib}}
| MedlinePlus = a620057
| DailyMedID = Pralsetinib
| pregnancy_AU = D
| pregnancy_category=
| routes_of_administration = By mouth
| class = Tyrosine kinase inhibitor
| ATC_prefix = L01
| ATC_suffix = EX23
| ATC_supplemental =
| legal_AU = S4
| legal_AU_comment = {{cite web | title=Gavreto pralsetinib 100 mg hard capsule bottle (380812) | website=Therapeutic Goods Administration (TGA) | date=30 March 2023 | url=https://www.tga.gov.au/resources/artg/380812 | access-date=7 April 2023 | archive-date=8 April 2023 | archive-url=https://web.archive.org/web/20230408034432/https://www.tga.gov.au/resources/artg/380812 | url-status=live }}{{cite web | title=Gavreto (Roche Products Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=26 April 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/gavreto-roche-products-pty-ltd | access-date=28 April 2023}}{{cite web | title=Gavreto (Roche Products Pty Ltd) | website=Therapeutic Goods Administration (TGA) | date=26 April 2023 | url=https://www.tga.gov.au/resources/prescription-medicines-registrations/gavreto-roche-products-pty-ltd-0 | access-date=28 April 2023}}{{Cite web | title=AusPAR: Gavreto {{!}} Therapeutic Goods Administration (TGA) | url=https://www.tga.gov.au/resources/auspar/auspar-gavreto-0 | archive-url=https://web.archive.org/web/20240331043845/https://www.tga.gov.au/resources/auspar/auspar-gavreto-0 | access-date=2025-04-05 | archive-date=2024-03-31}}
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| legal_BR_comment =
| legal_CA = Rx-only
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| legal_US = Rx-only
| legal_EU = Rx-only
| legal_EU_comment = {{cite web | title=Gavreto EPAR | website=European Medicines Agency (EMA) | date=14 September 2021 | url=https://www.ema.europa.eu/en/medicines/human/EPAR/gavreto | access-date=9 December 2021 | archive-date=10 December 2021 | archive-url=https://web.archive.org/web/20211210085329/https://www.ema.europa.eu/en/medicines/human/EPAR/gavreto | url-status=live }}{{cite web | title=Gavreto Product information | website=Union Register of medicinal products | url=https://ec.europa.eu/health/documents/community-register/html/h1555.htm | access-date=3 March 2023 | archive-date=5 March 2023 | archive-url=https://web.archive.org/web/20230305040638/https://ec.europa.eu/health/documents/community-register/html/h1555.htm | url-status=live }}
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| CAS_number = 2097132-94-8
| CAS_supplemental =
| PubChem = 129073603
| IUPHAR_ligand =
| DrugBank = DB15822
| ChemSpiderID = 71060332
| UNII = 1WPE73O1WV
| KEGG = D11712
| ChEBI =
| ChEMBL = 4297597
| NIAID_ChemDB =
| PDB_ligand =
| synonyms = BLU-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
| C = 27 | H = 32 | F = 1 | N = 9 | O = 2
| 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
| StdInChI = 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
| StdInChI_comment =
| StdInChIKey = GBLBJPZSROAGMF-SIYOEGHHSA-N
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Pralsetinib, sold under the brand name Gavreto, is a medication approved{{Cite web | work = Center for Drug Evaluation and Research |date=2021-06-11 |title=FDA approves pralsetinib for RET-altered thyroid cancers |url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-ret-altered-thyroid-cancers | publisher = U.S. Food and Drug Administration |language=en |access-date=9 January 2023 |archive-date=9 January 2023 |archive-url=https://web.archive.org/web/20230109101839/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-ret-altered-thyroid-cancers |url-status=live }} for RET mutation-positive medullary thyroid cancer (MTC){{cite journal | vauthors = Nervo A, Retta F, Ragni A, Piovesan A, Gallo M, Arvat E | title = Management of Progressive Radioiodine-Refractory Thyroid Carcinoma: Current Perspective | journal = Cancer Management and Research | volume = 14 | pages = 3047–3062 | date = 2022 | pmid = 36275786 | pmc = 9584766 | doi = 10.2147/CMAR.S340967 | doi-access = free }} and RET fusion-positive differentiated thyroid cancer (DTC) refractory to radioactive iodine (RAI) therapy. Pralsetinib is a tyrosine kinase inhibitor. It is taken by mouth.
The most common adverse reactions include increased aspartate aminotransferase (AST), decreased hemoglobin, decreased lymphocytes, decreased neutrophils, increased alanine aminotransferase (ALT), increased creatinine, increased alkaline phosphatase, fatigue, constipation, musculoskeletal pain, decreased calcium, hypertension, decreased sodium, decreased phosphate, and decreased platelets.
Pralsetinib was approved for medical use in the United States in September 2020,{{cite press release | publisher=Blueprint Medicines | title=Blueprint Medicines Announces FDA Approval of Gavreto (pralsetinib) for the Treatment of Adults with Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer | via=PR Newswire | date=4 September 2020 | url=https://www.prnewswire.com/news-releases/blueprint-medicines-announces-fda-approval-of-gavreto-pralsetinib-for-the-treatment-of-adults-with-metastatic-ret-fusion-positive-non-small-cell-lung-cancer-301124707.html | access-date=8 September 2020 | archive-date=9 September 2020 | archive-url=https://web.archive.org/web/20200909051400/https://www.prnewswire.com/news-releases/blueprint-medicines-announces-fda-approval-of-gavreto-pralsetinib-for-the-treatment-of-adults-with-metastatic-ret-fusion-positive-non-small-cell-lung-cancer-301124707.html | url-status=live }}{{cite press release | title=Roche announces FDA approval of Gavreto (pralsetinib) for the treatment of adults with metastatic RET fusion-positive non-small cell lung cancer | website=Roche | date=7 September 2020 | url=https://www.roche.com/media/releases/med-cor-2020-09-07.htm | access-date=8 September 2020 | archive-date=9 September 2020 | archive-url=https://web.archive.org/web/20200909051453/https://www.roche.com/media/releases/med-cor-2020-09-07.htm | url-status=live }}{{cite journal | vauthors = Markham A | title = Pralsetinib: First Approval | journal = Drugs | volume = 80 | issue = 17 | pages = 1865–1870 | date = November 2020 | pmid = 33136236 | doi = 10.1007/s40265-020-01427-4 | s2cid = 226223522 }}{{overcite|date=March 2024}} and in the European Union in November 2021.
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.{{cite web | title=FDA approves pralsetinib for lung cancer with RET gene fusions | website=U.S. Food and Drug Administration (FDA) | date=4 September 2020 | url=https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-lung-cancer-ret-gene-fusions | access-date=8 September 2020 | archive-date=9 September 2020 | archive-url=https://web.archive.org/web/20200909051417/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-pralsetinib-lung-cancer-ret-gene-fusions | url-status=live }} {{PD-notice}}{{cite web | title=Drug Trial Snapshot: Gavreto | website=U.S. Food and Drug Administration | date=4 September 2020 | url=https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-gavreto | access-date=16 September 2020 | archive-date=25 October 2020 | archive-url=https://web.archive.org/web/20201025213703/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trial-snapshot-gavreto | url-status=live }} {{PD-notice}}
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. Identification of RET gene alterations was prospectively determined in local laboratories using either next generation sequencing, fluorescence in situ hybridization, or other tests. The main efficacy outcome measures were overall response rate (ORR) and response duration determined by a blinded independent review committee using RECIST 1.1. The trial was conducted at sites in the United States, Europe and Asia.
Efficacy for RET fusion-positive NSCLC was evaluated in 87 participants previously treated with platinum chemotherapy. The ORR was 57% (95% CI: 46%, 68%); 80% of responding participants had responses lasting 6 months or longer. Efficacy was also evaluated in 27 participants who never received systemic treatment. The ORR for these participants was 70% (95% CI: 50%, 86%); 58% of responding participants had responses lasting 6 months or longer.
The US Food and Drug Administration (FDA) granted the application for pralsetinib priority review, orphan drug, and breakthrough therapy designationsand granted approval of Gavreto to Blueprint Medicines.
Society and culture
= Legal status =
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). The applicant for this medicinal product is Roche Registration GmbH.{{cite web | title=Gavreto: Pending EC decision | website=European Medicines Agency | date=17 September 2021 | url=https://www.ema.europa.eu/en/medicines/human/summaries-opinion/gavreto | access-date=17 September 2021 | archive-date=17 September 2021 | archive-url=https://web.archive.org/web/20210917190507/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/gavreto | url-status=live }} Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged. Pralsetinib was approved for medical use in the European Union in November 2021.
References
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External links
- {{cite web | title=Pralsetinib | publisher=National Cancer Institute | work=NCI Drug Dictionary | url=https://www.cancer.gov/publications/dictionaries/cancer-drug/def/ret-mutation-fusion-inhibitor-blu-667 }}
- {{ClinicalTrialsGov|NCT03037385|Phase 1/2 Study of the Highly-selective RET Inhibitor, Pralsetinib (BLU-667), in Patients With Thyroid Cancer, Non-Small Cell Lung Cancer, and Other Advanced Solid Tumors (ARROW)}}
- {{cite web | url=https://assets.ctfassets.net/srys4ukjcerm/1BSDoZrPAa4AVEa7ckC6l7/3bd17c9cc3308766640a31d211f20403/nsclc-infographic.pdf | title=Understanding Metastatic RET Fusion-Positive Non-Small Cell Lung Cancer (NSCLC) }}
- {{cite web | url=https://assets.ctfassets.net/srys4ukjcerm/71FAkBKkhOEWRN592GmqDk/dea684f9067934e5f93de7c90192c2db/thyroid-cancer-infographic.pdf | title=Understanding Metastatic RET-Driven Thyroid Cancers }}
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