Zanubrutinib Explained

Tradename:Brukinsa
Dailymedid:Zanubrutinib
Pregnancy Au:D
Pregnancy Au Comment:[1]
Routes Of Administration:By mouth
Class:Bruton's tyrosine kinase (BTK) inhibitor
Atc Prefix:L01
Atc Suffix:EL03
Legal Au:S4
Legal Au Comment:[2] [3] [4]
Legal Ca:Rx-only
Legal Ca Comment:[5]
Legal Us:Rx-only
Legal Us Comment:[6]
Legal Eu:Rx-only
Legal Eu Comment:[7]
Legal Status:Rx-only
Cas Number:1691249-45-2
Pubchem:135565884
Drugbank:DB15035
Chemspiderid:64835237
Unii:AG9MHG098Z
Kegg:D11422
Chembl:3936761
Pdb Ligand:BA0
Synonyms:BGB-3111
C:27
H:29
N:5
O:3
Smiles:NC(=O)C1=C2NCC[C@@H](C3CCN(CC3)C(=O)C=C)N2N=C1C1=CC=C(OC2=CC=CC=C2)C=C1
Stdinchi:1S/C27H29N5O3/c1-2-23(33)31-16-13-18(14-17-31)22-12-15-29-27-24(26(28)34)25(30-32(22)27)19-8-10-21(11-9-19)35-20-6-4-3-5-7-20/h2-11,18,22,29H,1,12-17H2,(H2,28,34)/t22-/m0/s1
Stdinchi Comment:[8]
Stdinchikey:RNOAOAWBMHREKO-QFIPXVFZSA-N

Zanubrutinib, sold under the brand name Brukinsa, is an anticancer medication used for the treatment of mantle cell lymphoma (MCL), Waldenström's macroglobulinemia (WM), marginal zone lymphoma (MZL), and chronic lymphocytic leukemia (CLL).[9] [10] [11] Zanubrutinib is classified as a Bruton's tyrosine kinase (BTK) inhibitor. It is given by mouth.

It was approved for medical use in the United States in November 2019.[12] [13] [14] [15] [16]

Medical uses

Zanubrutinib is indicated for the treatment of adults with mantle cell lymphoma who have received at least one prior therapy,[9] and for the treatment of Waldenström's macroglobulinemia.[17] It is also indicated for the treatment of adults with relapsed or refractory marginal zone lymphoma who have received at least one anti-CD20-based regimen.

In January 2023, the US Food and Drug Administration (FDA) approved zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma.[18]

In March 2024, FDA granted accelerated approval to zanubrutinib, in combination with obinutuzumab, for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.[19]

Adverse Effects

The most common adverse effects (≥30%) are: decreased neutrophil count, upper respiratory tract infection, decreased platelet count, hemorrhage and musculoskeletal pain.[20]

History

Efficacy was evaluated in BGB-3111-206 (NCT03206970), a phase II open-label, multicenter, single-arm trial of 86 participants with mantle cell lymphoma (MCL) who received at least one prior therapy.[14] Zanubrutinib was given orally at 160 mg twice daily until disease progression or unacceptable toxicity.[14] Efficacy was also assessed in BGB-3111-AU-003 (NCT02343120), a phase I/II, open-label, dose-escalation, global, multicenter, single-arm trial of B‑cell malignancies, including 32 previously treated MCL participants treated with zanubrutinib administered orally at 160 mg twice daily or 320 mg once daily.[14]

The primary efficacy outcome measure in both trials was overall response rate (ORR), as assessed by an independent review committee.[14] In trial BGB-3111-206, FDG-PET scans were required and the ORR was 84% (95% CI: 74, 91), with a complete response rate of 59% (95% CI 48, 70) and a median response duration of 19.5 months (95% CI: 16.6, not estimable).[14] In trial BGB-3111-AU-003, FDG-PET scans were not required and the ORR was 84% (95% CI: 67, 95), with a complete response rate of 22% (95% CI: 9, 40) and a median response duration of 18.5 months (95% CI: 12.6, not estimable).[14] Trial 1 was conducted at 13 sites in China, and Trial 2 was conducted at 25 sites in the United States, United Kingdom, Australia, New Zealand, Italy, and South Korea.

The U.S. Food and Drug Administration (FDA) granted zanubrutinib priority review, accelerated approval, breakthrough therapy, and orphan drug designations.[14] [21] The FDA approved zanubrutinib in November 2019, and granted the application for Brukinsa to BeiGene USA Inc.[22]

In August 2021, the FDA approved zanubrutinib for the treatment of Waldenström's macroglobulinemia and in September 2021, for marginal zone lymphoma (MZL).[23] [24] [25]

Zanubrutinib was investigated for Waldenström's macroglobulinemia in ASPEN (NCT03053440), a randomized, active control, open-label trial, comparing zanubrutinib and ibrutinib in participants with MYD88 L265P mutation (MYD88MUT) WM. Participants in Cohort 1 (n=201) were randomized 1:1 to receive zanubrutinib 160 mg twice daily or ibrutinib 420 mg once daily until disease progression or unacceptable toxicity. Cohort 2 enrolled participants with MYD88 wildtype (MYD88WT) or MYD88 mutation unknown WM (n=26 and 2, respectively) and received zanubrutinib 160 mg twice daily.

Approval of zanubrutinib for marginal zone lymphoma is based on two open-label, multicenter, single-arm trials: BGB-3111-214 (NCT03846427), which evaluated 66 participants with MZL who received at least one prior anti-CD20-based therapy, and BGB-3111-AU-003 (NCT02343120), which included 20 participants with previously treated MZL.

In March 2024, the FDA granted accelerated approval to zanubrutinib with obinutuzumab for relapsed or refractory follicular lymphoma after two or more lines of systemic therapy. The regimen was evaluated in Study BGB-3111-212 (ROSEWOOD; NCT03332017), an open-label, multicenter, randomized trial that enrolled 217 adult participants with relapsed or refractory follicular lymphoma after at least two prior systemic treatments. Participants were randomized (2:1) to receive either zanubrutinib 160 mg orally twice daily until disease progression or unacceptable toxicity plus obinutuzumab (ZO), or obinutuzumab alone. The median number of prior lines of therapy was 3 (range 2-11). The application was granted fast track and orphan drug designations.

Society and culture

Legal status

In 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 marketing authorization for the medicinal product Brukinsa, intended for the treatment of Waldenström's macroglobulinaemia.[26] The applicant for this medicinal product is BeiGene Ireland Ltd. Zanubrutinib was approved for medical use in the European Union in November 2021.[27]

External links

Notes and References

  1. Web site: Updates to the Prescribing Medicines in Pregnancy database . Therapeutic Goods Administration (TGA) . 12 May 2022 . 13 May 2022 . 3 April 2022 . https://web.archive.org/web/20220403064059/https://www.tga.gov.au/updates-prescribing-medicines-pregnancy-database . live .
  2. Web site: Brukinsa . Therapeutic Goods Administration (TGA) . 15 October 2021 . 22 October 2021 . 23 October 2021 . https://web.archive.org/web/20211023063959/https://www.tga.gov.au/apm-summary/brukinsa . live .
  3. Web site: Brukinsa . Therapeutic Goods Administration (TGA) . 20 October 2021 . 22 October 2021 . 23 October 2021 . https://web.archive.org/web/20211023065506/https://www.tga.gov.au/apm-summary/brukinsa-0 . live .
  4. Web site: Brukinsa (Beigene Aus Pty Ltd) . Therapeutic Goods Administration (TGA) . 5 December 2022 . 29 April 2023 . 18 March 2023 . https://web.archive.org/web/20230318044749/https://www.tga.gov.au/resources/prescription-medicines-registrations/brukinsa-beigene-aus-pty-ltd-1 . live .
  5. Web site: Summary Basis of Decision (SBD) for Brukinsa . Health Canada . 23 October 2014 . 29 May 2022 . 30 May 2022 . https://web.archive.org/web/20220530035600/https://hpr-rps.hres.ca/reg-content/summary-basis-decision-detailTwo.php?linkID=SBD00542&lang=en . live .
  6. Web site: Brukinsa- zanubrutinib capsule, gelatin coated . DailyMed . 1 September 2021 . 19 March 2021 . https://web.archive.org/web/20210319113103/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=3e08fe23-d70e-424c-bc51-1222e320f902 . live .
  7. Web site: Brukinsa EPAR . European Medicines Agency (EMA) . 19 July 2021 . 18 December 2021 . 19 December 2021 . https://web.archive.org/web/20211219043134/https://www.ema.europa.eu/en/medicines/human/EPAR/brukinsa . live .
  8. Web site: Zanubrutinib . DrugBank . 15 November 2019 . 15 November 2019 . https://web.archive.org/web/20191115205302/https://www.drugbank.ca/drugs/DB15035 . live .
  9. Sawalha Y, Bond DA, Alinari L . Evaluating the Therapeutic Potential of Zanubrutinib in the Treatment of Relapsed/Refractory Mantle Cell Lymphoma: Evidence to Date . OncoTargets and Therapy . 13 . 6573–6581 . 2020 . 32753893 . 7351990 . 10.2147/OTT.S238832 . free .
  10. Web site: FDA grants accelerated approval to zanubrutinib for marginal zone lymphoma . U.S. Food and Drug Administration (FDA) . 16 September 2021 . 16 September 2021 . 17 September 2021 . https://web.archive.org/web/20210917101558/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-marginal-zone-lymphoma . live .
  11. Web site: FDA Accepts sNDA for Zanubrutinib to Treat CLL/SLL . AJMC . 23 February 2022 . en . 28 July 2022 . 28 July 2022 . https://web.archive.org/web/20220728081723/https://www.ajmc.com/view/fda-accepts-snda-for-zanubrutinib-to-treat-cll-sll . live .
  12. Web site: Drug Approval Package: Brukinsa . U.S. Food and Drug Administration (FDA) . 27 November 2019 . 28 March 2020 . 28 November 2019 . https://web.archive.org/web/20191128051532/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/213217Orig1s000TOC.cfm . live .
  13. FDA approves therapy to treat patients with relapsed and refractory mantle cell lymphoma supported by clinical trial results showing high response rate of tumor shrinkage . U.S. Food and Drug Administration (FDA) . 14 November 2019 . 15 November 2019 . 15 November 2019 . https://web.archive.org/web/20191115031304/https://www.fda.gov/news-events/press-announcements/fda-approves-therapy-treat-patients-relapsed-and-refractory-mantle-cell-lymphoma-supported-clinical . live .
  14. FDA grants accelerated approval to zanubrutinib for mantle cell lymphoma . U.S. Food and Drug Administration (FDA) . 15 November 2019 . https://web.archive.org/web/20191128050259/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-zanubrutinib-mantle-cell-lymphoma . 28 November 2019 . live . 27 November 2019.
  15. Web site: Drug Trials Snapshots Brukinsa . U.S. Food and Drug Administration (FDA) . 14 November 2019 . 26 January 2020 . 23 January 2021 . https://web.archive.org/web/20210123124234/https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-brukinsa . live .
  16. Syed YY . Zanubrutinib: First Approval . Drugs . 80 . 1 . 91–97 . January 2020 . 31933167 . 10.1007/s40265-019-01252-4 . 210158252 .
  17. Web site: FDA approves zanubrutinib for Waldenström's macroglobulinemia . U.S. Food and Drug Administration (FDA) . 1 September 2021 . 1 September 2021 . 1 September 2021 . https://web.archive.org/web/20210901225739/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-waldenstroms-macroglobulinemia . live .
  18. Web site: FDA approves zanubrutinib for chronic lymphocytic leukemia or small lymphocytic lymphoma . U.S. Food and Drug Administration (FDA) . 19 January 2023 . 26 January 2023 . 25 January 2023 . https://web.archive.org/web/20230125210557/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-zanubrutinib-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma . live .
  19. Web site: FDA grants accelerated approval to zanubrutinib for relapsed or refractory follicular lymphoma . U.S. Food and Drug Administration (FDA) . 7 March 2024 . 9 March 2024.
  20. Web site: HIGHLIGHTS OF PRESCRIBING INFORMATION . US Food and Drug Administration . 2 April 2024.
  21. Web site: Zanubrutinib Orphan Drug Designation and Approval . U.S. Food and Drug Administration (FDA) . 28 November 2019 . https://web.archive.org/web/20191128051210/https://www.accessdata.fda.gov/scripts/opdlisting/oopd/detailedIndex.cfm?cfgridkey=527416 . 28 November 2019 . live . 27 November 2019.
  22. Web site: Drug Approval Package: Brukinsa . U.S. Food and Drug Administration (FDA) . 27 November 2019 . https://web.archive.org/web/20191128051532/https://www.accessdata.fda.gov/drugsatfda_docs/nda/2019/213217Orig1s000TOC.cfm . 28 November 2019 . live . 27 November 2019.
  23. U.S. FDA Grants Brukinsa (Zanubrutinib) Approval in Waldenström's Macroglobulinemia . BeiGene . 1 September 2021 . 1 September 2021 . 2 September 2021 . https://web.archive.org/web/20210902042407/https://ir.beigene.com/news-details/?id=802fb825-acb1-455d-b916-c95068817a9d . live .
  24. U.S. FDA Grants Brukinsa (Zanubrutinib) Approval in Waldenström's Macroglobulinemia . BeiGene . Business Wire . 1 September 2021 . 1 September 2021 . 2 September 2021 . https://web.archive.org/web/20210902042406/https://www.businesswire.com/news/home/20210901006049/en/ . live .
  25. Web site: U.S. FDA Grants Brukinsa (Zanubrutinib) Accelerated Approval in Relapsed or Refractory Marginal Zone Lymphoma . BeiGene . Business Wire . 15 September 2021 . 16 September 2021 . 16 September 2021 . https://web.archive.org/web/20210916014213/http://www.businesswire.com/news/home/20210915005310/en/U.S.-FDA-Grants-BRUKINSA%C2%AE-Zanubrutinib-Accelerated-Approval-in-Relapsed-or-Refractory-Marginal-Zone-Lymphoma/ . live .
  26. Web site: Brukinsa: Pending EC decision . European Medicines Agency . 17 September 2021 . 17 September 2021 . 17 September 2021 . https://web.archive.org/web/20210917185834/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/brukinsa . live . Text was copied from this source which is copyrighted by European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
  27. Web site: Brukinsa Product information . Union Register of medicinal products . 3 March 2023 . 4 March 2023 . https://web.archive.org/web/20230304104709/https://ec.europa.eu/health/documents/community-register/html/h1576.htm . live .

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