Brigatinib

{{More citations needed section|date=March 2022}}

Brigatinib is an inhibitor of ALK and mutated EGFR.

ALK was first identified as a chromosomal rearrangement in anaplastic large cell lymphoma (ALCL). Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC) and neuroblastomas, as well as ALCL. Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy.

Brigatinib inhibits ROS proto-oncogene-1 fusions and EGFR mutations and has a remarkable effect on the central nervous system.{{cite journal | vauthors = Patcas A, Chis AF, Militaru CF, Bordea IR, Rajnoveanu R, Coza OF, Hanna R, Tiberiu T, Todea DA | display-authors = 6 | title = An insight into lung cancer: a comprehensive review exploring ALK TKI and mechanisms of resistance | journal = Bosnian Journal of Basic Medical Sciences | volume = 22 | issue = 1 | pages = 1–13 | date = February 2022 | pmid = 34082691 | pmc = 8860314 | doi = 10.17305/bjbms.2021.5859 }}

Epidermal growth factor receptor (EGFR) is another validated target in NSCLC. Additionally, the T790M "gatekeeper" mutation is linked in approximately 50 percent of patients who grow resistant to first-generation EGFR inhibitors.{{cite journal | vauthors = Sequist LV, Waltman BA, Dias-Santagata D, Digumarthy S, Turke AB, Fidias P, Bergethon K, Shaw AT, Gettinger S, Cosper AK, Akhavanfard S, Heist RS, Temel J, Christensen JG, Wain JC, Lynch TJ, Vernovsky K, Mark EJ, Lanuti M, Iafrate AJ, Mino-Kenudson M, Engelman JA | display-authors = 6 | title = Genotypic and histological evolution of lung cancers acquiring resistance to EGFR inhibitors | journal = Science Translational Medicine | volume = 3 | issue = 75 | pages = 75ra26 | date = March 2011 | pmid = 21430269 | pmc = 3132801 | doi = 10.1126/scitranslmed.3002003 }} While second-generation EGFR inhibitors are in development, clinical efficacy has been limited due to toxicity thought to be associated with inhibiting the native (endogenous or unmutated) EGFR. A therapy designed to target EGFR, the T790M mutation but avoiding inhibition of native EGFR is another promising molecular target for cancer therapy.

Ariad Pharmaceuticals, Inc. filed an investigational new drug (IND) application to the US FDA on August 29, 2016.{{Cite web|url= https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/208772Orig1s000MultidisciplineR.pdf |title= NDA 208772 Multidisciplinary Review and Evaluation Alunbrig (brigatinib) |date=29 August 2016 |website= FDA.gov|access-date=31 October 2017}}

In 2016, brigatinib was granted orphan drug status by the FDA for treatment of NSCLC.{{Cite web | url=http://www.ariad.com/research-development/brigatinib/ | archive-url = https://web.archive.org/web/20161230023339/http://www.ariad.com/research-development/brigatinib/ | archive-date = 30 December 2016 | title=About Brigatinib | work = ARIAD Pharmaceuticals, Inc }}

On 28 April 2017, it was granted an accelerated approval from the U.S. Food and Drug Administration (FDA) for metastatic non-small cell lung cancer (NSCLC);{{cite web | url = https://www.cancer.gov/news-events/cancer-currents-blog/2017/brigatinib-fda-lung-cancer | title = FDA Grants Brigatinib Accelerated Approval for Metastatic Non-Small Cell Lung Cancer | work = National Cancer Institute | date = 19 May 2017 | publisher = U.S. Department of Health and Human Services }}{{cite web | url = https://www.takeda.com/newsroom/newsreleases/2017/alunbrig-fda-approval/ | title = Takeda Announces FDA Accelerated Approval of Alunbrig (brigatinib) | work = Takeda Pharmaceuticals }} as a 2nd-line therapy for ALK-positive NSCLC.{{citation needed|date=March 2022}}

In 2020, it was approved as first-line treatment for ALK-positive metastatic NSCLC patients.

On 22 April 2015, Ariad Pharmaceuticals, Inc. announced the issuance of its first U.S. patent on brigatinib, the protection is through December 30, 2030. The United States Patent and Trademark Office granted U.S. Patent No. 9,012,462 under the title, "Phosphorous Derivatives as Kinase Inhibitors."{{Cite web |url=https://patents.google.com/patent/US9012462B2/en |date=9 July 2023 |access-date=7 July 2023 |title=Phosphorous derivatives as kinase inhibitors }}

Brigatinib is manufactured by Ariad Pharmaceuticals, Inc. (NASDAQ: ARIA) which is focused on rare cancers. Ariad then was acquired by Takeda Pharmaceutical Company Limited (TSE: 4502) in February 2017 through a tender offer (for $24.00 per share in cash) and subsequent merger of Ariad with Kiku Merger Co., Inc., a wholly owned subsidiary of Takeda Pharmaceuticals U.S.A. Ariad is an indirect wholly owned subsidiary of Takeda.{{Cite web|url=https://www.takeda.com/newsroom/newsreleases/2017/Takeda-Completes-Acquisition-of-ARIAD-Pharmaceuticals-Inc/ |title=Takeda Completes Acquisition of Ariad Pharmaceuticals, Inc. |date=26 February 2017 |website= takeda.com |access-date=31 October 2017}}

Brigatinib is the INN.{{cite web | title = International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 75 | url =https://www.who.int/medicines/publications/druginformation/innlists/RL75.pdf | publisher = World Health Organization | access-date = 14 February 2017 | page = 104 | date = 2016}}

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{{Targeted cancer therapeutic agents}}

{{Growth factor receptor modulators}}

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