Ceritinib

Ceritinib
Clinical data
Pronunciation/səˈrɪtɪnɪb/ sə-RIT-i-nib
Trade namesZykadia, others
Other namesLDK378
AHFS/Drugs.comMonograph
MedlinePlusa614027
License data
Routes of
administration		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
BioavailabilityNot determined
Protein binding97%
MetabolismCYP3A
Elimination half-life41 hours
ExcretionFeces (92.3%), urine (1.3%)[5]
Identifiers
  • 5-Chloro-N2-{5-methyl-4-(piperidin-4-yl)-2-[(propan-2-yl)oxy]phenyl}-N4-[2-(propane-2-sulfonyl)phenyl]pyrimidine-2,4-diamine
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.241.919 Edit this at Wikidata
Chemical and physical data
FormulaC28H36ClN5O3S
Molar mass558.14 g·mol−1
3D model (JSmol)
  • CC1=CC(=C(C=C1C2CCNCC2)OC(C)C)NC3=NC=C(C(=N3)NC4=CC=CC=C4S(=O)(=O)C(C)C)Cl
  • InChI=1S/C28H36ClN5O3S/c1-17(2)37-25-15-21(20-10-12-30-13-11-20)19(5)14-24(25)33-28-31-16-22(29)27(34-28)32-23-8-6-7-9-26(23)38(35,36)18(3)4/h6-9,14-18,20,30H,10-13H2,1-5H3,(H2,31,32,33,34)
  • Key:VERWOWGGCGHDQE-UHFFFAOYSA-N

Ceritinib (INN,[6] trade name Zykadia /zaɪˈkeɪdiːə/ zy-KAY-dee-ə) is a prescription-only drug used for the treatment of non-small cell lung cancer (NSCLC).[7] It was developed by Novartis and received FDA approval for use in April 2014.[7]

Medical uses

Ceritinib is an anaplastic lymphoma kinase (ALK) inhibitor primarily used for the treatment of ALK positive metastatic NSCLC.[8][9] Previously, it was only indicated for patients who had developed resistant to crizotinib, another ALK inhibitor, but has since had its usage expanded to serve as a primary option for metastatic NSCLC.[10]

Adverse effects

Serious adverse effects include gastrointestinal toxicity, hepatotoxicity, interstitial lung disease, prolonged QT syndrome, hyperglycemia, bradycardia, and pancreatitis.[11]

The most commonly reported side effects were diarrhea, nausea, elevated liver enzymes, vomiting, abdominal pain, fatigue, decreased appetite, and constipation.[8]

Interactions

Ceritinib is both a substrate and potent inhibitor of the enzyme CYP3A4, so medications that have affinity for this enzyme may interact with ceritinib.

Pharmacology

Mechanism of action

Ceritinib is a tyrosine kinase inhibitor that selectively and potently inhibits anaplastic lymphoma kinase (ALK). In normal physiology, ALK functions as a key step in the development and function of nervous system tissue. However, chromosomal translocation and fusion give rise to an oncogenic form of ALK that has been implicated in progression of NSCLC. Ceritinib thus acts to inhibit this mutated enzyme and stop cell proliferation, ultimately halting cancer progression.[12] Because ceritinib is considered a targeted cancer therapy, an FDA-approved test is required to determine which patients are candidates for ceritinib. This test, developed by Roche, is the VENTANA ALK (D5F3) CDx Assay and is used to identify ALK-positive NSCLC patients who would benefit from ceritinib treatment.[13]

Research and development

Researchers first identified the ALK fusion gene in 1994. Several years later, Novartis Pharmaceuticals Corporation, began working towards development of targeted ALK inhibitors. In April 2014, the FDA granted accelerated approval for ceritinib when used for ALK-positive NSCLC patients who have progressed on or are intolerant to crizotinib (Xalkori, Pfizer, Inc.). This rapid approval was determined from a multi-center clinical trial in which 163 patients who had disease progression or were intolerant to crizotinib received oral ceritinib 750 mg once daily. This trial demonstrated an objective response rate (ORR) of 44% and a median duration of response (DOR) of 7.1 months, both of which were favorable compared to the worsening or failed use of crizotinib.[14]

In February 2017, the FDA accepted a supplement New Drug Application for ceritinib and granted Priority Review for expanded use of ceritinib. Specifically, it became a first-line therapy option for metastatic NSCLC with ALK-positive tumors. Additionally, the FDA also gave Breakthrough Therapy designation to the drug for ALK-positive metastatic NSCLC that has metastasized to the brain.[15] This new designation resulted from the ASCEND-4 clinical trial, which was a randomized, phase III study that compared the use of ceritinib to standard-of-care platinum-based chemotherapy treatments. Median progression-free survival was 16.6 months for ceritinib (n=189) versus 8.1 months in the chemotherapy-treated patients (n=187).[16]

Society and culture

Economics

Zykadia is manufactured by Novartis.[17] Created in 1996 from a merger between Ciba-Geigy and Sandoz, Novartis is a global corporation based out of Basel, Switzerland.[18] Over 155 countries worldwide have Novartis products available for use.[19] Financial data from 2016 reveals net sales of $48.5 billion for the Swiss company.[19]

Novartis divides its shares into two major market exchanges: the ordinary shares (NOVN SW) trade in the Six Swiss Exchange while the American Depositary Receipts (NVS US) trade in the New York Stock Exchange.[20] Nominees, fiduciaries, and ADR depositary make up the bulk of registered shareholders of Novartis stock while individual shareholders make up the lowest percentage.[21]

Originally launched in 2014, Zykadia sales for Fiscal Year 2016 reached $91 million.[22] While this is substantially less than several of their other pharmaceuticals, the new indication introduced in 2017 should result in increased sales of the drug. GlobalData predicts ceritinib sales to exceed $127million by 2025, while sustaining a compounded annual growth rate of 10.7%.[23]

Intellectual property

Novartis currently owns twelve patents on Zykadia.[24] The patents relate to different structures[clarification needed] of the chemical compound as well as methodologies for manufacturing the drug. For example, one patent examines the structure of pyrimidines and their use in treatment of neoplastic diseases.[25] Others examine the composition of protein kinase inhibitors.[26] The most recent patents are specific the methodologies of using ALK inhibitors.[27]

Brand names

Ceritinib is also sold under the brand name Spexib in some countries by Novartis.[citation needed]

References

  1. ^ "Prescription medicines: registration of new chemical entities in Australia, 2016". Therapeutic Goods Administration (TGA). 21 June 2022. Archived from the original on 10 April 2023. Retrieved 10 April 2023.
  2. ^ "Health Canada New Drug Authorizations: 2015 Highlights". Health Canada. 4 May 2016. Retrieved 7 April 2024.
  3. ^ "Zykadia- ceritinib tablet, film coated". DailyMed. 11 January 2024. Retrieved 13 June 2024.
  4. ^ "Zykadia EPAR". European Medicines Agency. 6 May 2015. Retrieved 13 June 2024.
  5. ^ "Zykadia (ceritinib) Capsules, for Oral Use. Full Prescribing Information" (PDF). Novartis Pharmaceuticals Corporation. Retrieved 14 February 2017.
  6. ^ "International Nonproprietary Names for Pharmaceutical Substances (INN). Recommended International Nonproprietary Names: List 71" (PDF). World Health Organization. 2014. p. 79. Retrieved 14 February 2017.
  7. ^ a b "FDA Approves Ceritinib for ALK-Positive Lung Cancer". Medscape. 29 April 2014.
  8. ^ a b "Prescribing data" (PDF). www.pharma.us.novartis.com. Retrieved 12 June 2019.
  9. ^ Deeks ED (October 2016). "Ceritinib: a Review in ALK-Positive Advanced NSCLC". Targeted Oncology. 11 (5): 693–700. doi:10.1007/s11523-016-0460-7. PMID 27699584. S2CID 24118254.
  10. ^ "FDA Expands Ceritinib Approval for Lung Cancer". National Cancer Institute. 27 June 2017.
  11. ^ Au TH, Cavalieri CC, Stenehjem DD (December 2017). "Ceritinib: A primer for pharmacists". Journal of Oncology Pharmacy Practice. 23 (8): 602–614. doi:10.1177/1078155216672315. PMID 27738095. S2CID 12034087.
  12. ^ "Analplastic lymphoma kinase (ALK) fusion oncogene positive non-small cell lung cancer". UpToDate. Wolters Kluwer. Retrieved 30 October 2017.
  13. ^ "Roche announces FDA approval of companion diagnostic to identify ALK-positive non-small cell lung cancer patients". diagnostics.roche.com. Archived from the original on 26 April 2019. Retrieved 12 June 2019.
  14. ^ Khozin S, Blumenthal GM, Zhang L, Tang S, Brower M, Fox E, et al. (June 2015). "FDA approval: ceritinib for the treatment of metastatic anaplastic lymphoma kinase-positive non-small cell lung cancer". Clinical Cancer Research. 21 (11): 2436–2439. doi:10.1158/1078-0432.CCR-14-3157. PMID 25754348.
  15. ^ "Novartis drug Zykadia receives FDA Priority Review for first-line use in patients with ALK+ metastatic NSCLC". Novartis. Archived from the original on 26 April 2019. Retrieved 1 November 2017.
  16. ^ Soria JC, Tan DS, Chiari R, Wu YL, Paz-Ares L, Wolf J, et al. (March 2017). "First-line ceritinib versus platinum-based chemotherapy in advanced ALK-rearranged non-small-cell lung cancer (ASCEND-4): a randomised, open-label, phase 3 study". Lancet. 389 (10072): 917–929. doi:10.1016/s0140-6736(17)30123-x. PMID 28126333. S2CID 4739527.
  17. ^ "Brochure" (PDF). www.us.zykadia.com. Retrieved 12 June 2019.
  18. ^ "Novartis Company History". Novartis Global. Archived from the original on 7 November 2017. Retrieved 3 November 2017.
  19. ^ a b "Novartis Annual Reporting Suite". Novartis.
  20. ^ "Share Overview". Novartis.
  21. ^ "Share Ownership". Novartis.
  22. ^ "Interim financial report" (PDF). www.novartis.com. 2017. Archived from the original (PDF) on 4 December 2020. Retrieved 12 June 2019.
  23. ^ Xuan C, Gunduz V. "NSCLC MARKET – Global Drug Forecast & Market Analysis to 2025". Drug Development & Delivery. No. November–December 2016.
  24. ^ "Zykadia - Patents - Expiry - Expiration - Dates". PharmaCompass.com.
  25. ^ "US Patent No.: 7964592" (PDF). PharmaCompass. Retrieved 1 November 2017.
  26. ^ "US No.: 8399450". PharmaCompass. Retrieved 1 November 2017.
  27. ^ "US No.: 8703787". PharmaCompass. Retrieved 1 November 2017.
  • Media related to Ceritinib at Wikimedia Commons

Read other articles:

kubus

Halaman ini berisi artikel tentang bangun ruang berdimensi tiga. Untuk kubus dalam sebarang dimensi, lihat Hiperkubus. KubusKubus berbentuk heksahedron.Jenisbangun ruang PlatonikMuka6Rusuk12titik sudut8Konfigurasi titik sudutV 3.3.3.3Simbol Wythoff3Simbol Schläfli{4,3}Diagram CoxeterGrup simetriOh, B3, [4,3], (* 432)Sudut dihedral (derajat)90°Sifat-sifatberaturan, cembung zonohedronJaring Kubus dalam 3D Dalam geometri, kubus adalah bangun ruang tiga dimensi yang dibatasi oleh enam bidang si...

 

 

تاريخ الطب في الولايات المتحدة

هذه المقالة بحاجة لصندوق معلومات. فضلًا ساعد في تحسين هذه المقالة بإضافة صندوق معلومات مخصص إليها. يشمل تاريخ الطب في الولايات المتحدة مجموعة متنوعة من الفترات والمناهج المتعلقة بالرعاية الصحية في الولايات المتحدة من أيام الاستعمار إلى الوقت الحاضر، والتي تتراوح من علاج�...

 

 

Apt. (film)

APTPoster rilis teatrikalNama lainHangul아파트 Alih AksaraApateuMcCune–ReischauerAp‘at‘ŭ SutradaraAhn Byeong-kiProduserAhn Byeong-kiDitulis olehAhn Byeong-kiLee So-yeongBerdasarkanAPToleh Kang FullPemeranKo So-youngKang Sung-jinJang Hee-jinPark Ha-sunYoo MinPenata musikOh Bong-junSinematograferYun Myeong-sikPenyuntingKim Sun-minPerusahaanproduksiToilet PicturesIM Pictures Corp.MirovisionDistributorShowboxTanggal rilis 06 Juli 2006 (2006-07-06) Durasi90 menitNegaraKo...

1992 United States presidential election in Maryland

U.S. presidential election in Maryland Main article: 1992 United States presidential election 1992 United States presidential election in Maryland ← 1988 November 3, 1992 1996 →   Nominee Bill Clinton George H. W. Bush Ross Perot Party Democratic Republican Independent Home state Arkansas Texas Texas Running mate Al Gore Dan Quayle James Stockdale Electoral vote 10 0 0 Popular vote 988,571 707,094 281,414 Percentage 49.80% 35.62% 14.18% County Re...

 

 

Vol (command)

volThe Windows XP vol commandDeveloper(s)DR, Microsoft, IBM, Toshiba, ReactOS ContributorsInitial releaseMarch 1983; 41 years ago (1983-03)Operating systemMS-DOS, PC DOS, MSX-DOS, FlexOS, SISNE plus, OS/2, eComStation, ArcaOS, DR DOS, ROM-DOS, 4690 OS, PTS-DOS, Windows, FreeDOS, ReactOSPlatformCross-platformTypeCommand In some operating systems, vol is a command within the command-line interpreters (shells) such as COMMAND.COM and cmd.exe. It is used to display the volu...

 

 

Luigi Cherubini

« Cherubini » redirige ici. Pour les autres significations, voir Cherubini (homonymie). Si ce bandeau n'est plus pertinent, retirez-le. Cliquez ici pour en savoir plus. Cet article ne cite pas suffisamment ses sources (janvier 2023). Si vous disposez d'ouvrages ou d'articles de référence ou si vous connaissez des sites web de qualité traitant du thème abordé ici, merci de compléter l'article en donnant les références utiles à sa vérifiabilité et en les liant à la sect...

Mikael Stanne

Swedish metal vocalist Mikael StanneStanne in 2007Background informationBirth nameBengt Mikael StanneBorn (1974-05-20) 20 May 1974 (age 49)Gothenburg, SwedenGenresMelodic death metalOccupation(s)SingersongwriterYears active1989–presentMember ofDark TranquillityThe Halo EffectGrand CadaverCemetery SkylineFormerly ofIn FlamesHammerFallMusical artist Bengt Mikael Stanne[1] (born 20 May 1974) is a Swedish musician, best known as the vocalist and a former rhythm guitarist for the m...

 

 

ロバート・デ・ニーロ

ロバート・デ・ニーロRobert De Niro 2011年のデ・ニーロ生年月日 (1943-08-17) 1943年8月17日（80歳）出生地 アメリカ合衆国・ニューヨーク州ニューヨーク市身長 177 cm職業 俳優、映画監督、映画プロデューサージャンル 映画、テレビドラマ活動期間 1963年 -配偶者 ダイアン・アボット（1976年 - 1988年）グレイス・ハイタワー（1997年 - ）主な作品 『ミーン・ストリート』（1973年）...

 

 

Northrop Grumman X-47A Pegasus

Northrop Grumman X-47 adalah pesawat militer nirawak demonstrasi buatan Northrop Grumman Amerika Serikat. X-47 dimulai sebagai bagian dari program DARPA J-UCAS, dan kini menjadi bagian dari program UCAS-D Angkatan Laut Amerika Serikat untuk membuat pesawat nirawak berbasis kapal induk.[1][2][3] Kendaraan asli membawa penunjukan X-47A Pegasus, sedangkan pada versi angkatan laut adalah X-47B.[4] Angkatan Laut AS tidak berkomitmen untuk upaya UCAV praktis sampai ...

Стеллерова корова

† Стеллерова корова Муляж стеллеровой коровы в Лондонском музее естествознания Научная классификация Домен:ЭукариотыЦарство:ЖивотныеПодцарство:ЭуметазоиБез ранга:Двусторонне-симметричныеБез ранга:ВторичноротыеТип:ХордовыеПодтип:ПозвоночныеИнфратип:Челюстно�...

 

 

Harriet Forten Purvis

American abolitionist (1810–1875) Harriet Forten PurvisPurvis c. 1874[1]BornHarriet Davy Fortenc. 1810Philadelphia, Pennsylvania, USDiedJune 11, 1875 (aged 64–65)Washington, D.C., USOther namesHattie Purvis Jr.OccupationsAbolitionistsuffragetteUnderground Railroad station ownerSpouseRobert PurvisChildren8, including Harriet Jr. and CharlesParentsJames Forten (father)Charlotte Vandine Forten (mother)RelativesSarah Louisa Forten Purvis (sister)Margaretta Forten (...

 

 

新罕布什尔州

坐标：43°11′38″N 71°34′21″W / 43.1938516°N 71.5723953°W / 43.1938516; -71.5723953 此條目需要补充更多来源。 (2017年5月21日)请协助補充多方面可靠来源以改善这篇条目，无法查证的内容可能會因為异议提出而被移除。致使用者：请搜索一下条目的标题（来源搜索：新罕布什尔州 — 网页、新闻、书籍、学术、图像），以检查网络上是否存在该主题的更多可靠来源...

Тарасівка (Гребінківська міська громада)

У Вікіпедії є статті про інші населені пункти з такою назвою: Тарасівка. село Тарасівка Пам'ятник Т.Г.Шевченку (фото 2008 року)Пам'ятник Т.Г.Шевченку (фото 2008 року) Країна  Україна Область Полтавська область Район Лубенський район Громада Гребінківська міська громада Код �...

 

 

متر

مترمعلومات عامةالنوع وحدة دولية أساسية[1][2] — وحدة مسافة — وحدة متماسكة حسب نظام الوحدات الدولي — UCUM base unit (en) جزء من MKSA system of units (en) — نظام الوحدات الدولي — نظام وحدات متر كيلوغرام ثانية تستخدم لقياس  القائمة ... طول[3][4] — مسافة — متجه موضع — diffusion coefficient for...

 

 

Combustible

Le combustible consommé dans une cheminée traditionnelle est généralement du bois. Un combustible est un composé chimique qui, avec un comburant (comme le dioxygène) et de l'énergie, se consume dans une réaction chimique générant de la chaleur : la combustion. Cette réaction d'oxydation exothermique rapide fait intervenir un réactif réducteur (combustible), et un réactif oxydant (comburant). Un carburant est un combustible qui alimente un moteur à combustion interne. On pa...

World Scout Jamboree

Large-scale youth event which occurs every four years World Scout JamboreeScouts at the 22nd World Scout Jamboree in Rinkaby, Sweden (2011)OwnerWorld Organization of the Scout MovementDate1920  Scouting portal The World Scout Jamboree is a Scouting jamboree of the World Organization of the Scout Movement, typically attended by several tens of thousands of Scouts from around the world, aged 14 to 17. At the jamboree, many scouts swap badges. The first World Scout Jamboree was organized by...

 

 

المصرية للغازات الطبيعية

محتوى هذه المقالة بحاجة للتحديث. فضلًا، ساعد بتحديثه ليعكس الأحداث الأخيرة وليشمل المعلومات الموثوقة المتاحة حديثًا. (مارس 2019) المصرية للغازات الطبيعيةجاسكو المصرية للغازات الطبيعيةالشعارمعلومات عامةالبلد  مصر التأسيس 1997النوع شركة مساهمةالمقر الرئيسي التجمع الخامس ...

 

 

Yoon Do-hyun

Dalam nama Korean ini, nama keluarganya adalah Yoon. Yoon Do-hyunLahir3 Februari 1972 (umur 52)Paju, Provinsi Gyeonggi, Korea SelatanPendidikanIncheon City College – Civil Engineering Universitas Sungkonghoe – Media dan KomunikasiPekerjaanPenyanyi, musisi, penulis lagu, MC, aktorTahun aktif1993–presentAgenDee CompanySuami/istriLee Mi-ok (m. 2002)Nama KoreaHangul윤도현 Hanja尹度玹 Alih AksaraYun Do-hyeonMcCune–ReischauerYun To-hyŏn Situs webdeecompany.kr Yoon Do-hyun (...

Édouard André

Édouard François André Édouard François André (17 Juli 1840 – 25 Oktober 1911) merupakan seorang hortikulturis Prancis, perancang lanskap, serta arsitek lanskap terkemuka pada akhir abad kesembilan belas. Ia terkenal karena merancang taman kota dan tempat umum di Monte Carlo dan Montevideo. Daftar pustaka Bromeliaceae Andreanae. Description et Histoire des Bromeliacées, récoltées dans la Colombie, l'Ecuador et la Venezuela. Paris: Librairie Agricole, 1889. Nachdruck: Berkeley CA, U...

 

 

Kazimierz Kuratowski

Polish mathematician and logician Kazimierz KuratowskiKuratowski in 1959Born(1896-02-02)2 February 1896Warsaw, Congress Poland, Russian EmpireDied18 June 1980(1980-06-18) (aged 84)Warsaw, PolandNationalityPolishAlma materUniversity of WarsawKnown forKuratowski's theoremKuratowski closure axiomsKuratowski–Zorn lemmaKuratowski's closure-complement problemKuratowski's intersection theoremKuratowski-Ulam theoremKuratowski-finiteKuratowski and Ryll-Nardzewski measurable selection ...