Pirtobrutinib Explained

Tradename:Jaypirca
Dailymedid:Pirtobrutinib
Routes Of Administration:By mouth
Class:Protein kinase inhibitor
Atc Prefix:L01
Atc Suffix:EL05
Legal Us:Rx-only
Legal Eu:Rx-only
Legal Eu Comment:[1] [2]
Cas Number:2101700-15-4
Pubchem:129269915
Drugbank:DB17472
Chemspiderid:114875989
Unii:JNA39I7ZVB
Kegg:D12050
Chebi:229212
Chembl:4650485
Pdb Ligand:Y7W
Synonyms:LOXO-305
Iupac Name:5-amino-3-[4-[<nowiki/>[(5-fluoro-2-methoxybenzoyl)amino]methyl]phenyl]-1-[(2S)-1,1,1-trifluoropropan-2-yl]pyrazole-4-carboxamide
C:22
H:21
F:4
N:5
O:3
Smiles:COC1=C(C=C(F)C=C1)C(=O)NCC1=CC=C(C=C1)C1=NN([C@@H](C)C(F)(F)F)C(N)=C1C(N)=O
Stdinchi:1S/C22H21F4N5O3/c1-11(22(24,25)26)31-19(27)17(20(28)32)18(30-31)13-5-3-12(4-6-13)10-29-21(33)15-9-14(23)7-8-16(15)34-2/h3-9,11H,10,27H2,1-2H3,(H2,28,32)(H,29,33)/t11-/m0/s1
Stdinchikey:FWZAWAUZXYCBKZ-NSHDSACASA-N

Pirtobrutinib, sold under the brand name Jaypirca, is an anticancer medication that is used to treat mantle cell lymphoma.[3] It inhibits B cell lymphocyte proliferation and survival by binding and inhibiting Bruton's tyrosine kinase (BTK).[4] It is taken by mouth.

The most common adverse reactions include fatigue, musculoskeletal pain, diarrhea, edema, dyspnea, pneumonia, and bruising. The most common adverse reactions when used to treat chronic lymphocytic leukemia or small lymphocytic leukemia include fatigue, bruising, cough, musculoskeletal pain, COVID-19, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache.

Pirtobrutinib was approved for medical use in the United States in January 2023,[5] [6] [7] and in the European Union in November 2023.

Medical uses

In the United States, pirtobrutinib is indicated to treat relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a Bruton's tyrosine kinase (BTK) inhibitor.[8] [9] In December 2023, the US Food and Drug Administration (FDA) expanded the indication for pirtobrutinib to include the treatment of adults with chronic lymphocytic leukemia or small lymphocytic leukemia.[10] [11]

In the European Union, pirtobrutinib is indicated for the treatment of mantle cell lymphoma.

Mechanism of action

B cells are white cells of the lymphocyte subtype that produce antibodies, but when some of them grow uncontrollably they can be a cause of cancer. A key enzyme in B cell stimulation and survival is BTK, and pirtobrutinib inhibits BTK in a way that is different from the prototypical BTK inhibitor ibrutinib by binding in a different way that avoids a genetic change (mutation at active site cysteine residue C481 in BTK) that can make some tumors less responsive to ibrutinib.

History

Pirtobrutinib is manufactured by Eli Lilly and Company and was approved by the US Food and Drug Administration in January 2023, for the treatment of mantle cell lymphoma that has become refractory to other BTK inhibitors.[12]

Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 participants with mantle cell lymphoma previously treated with a Bruton's tyrosine kinase (BTK) inhibitor. Participants had a median of three prior lines of therapy, with 93% having two or more prior lines. The most common prior Bruton's tyrosine kinase inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% had discontinued their last Bruton's tyrosine kinase inhibitor due to refractory or progressive disease. The trial was conducted at 49 sites in 10 countries in the United States, Europe, Australia, and Asia. The same trial was used to assess safety and efficacy.[13]

Efficacy was evaluated in BRUIN (NCT03740529], an open-label, international, single-arm, multicohort trial that included 108 participants with chronic lymphocytic leukemia or small lymphocytic lymphoma previously treated with at least two prior lines of therapy, including a Bruton's tyrosine kinase (BTK) inhibitor and a B-cell lymphoma-2 (BCL-2) inhibitor. Participants received a median of five prior lines of therapy (range: 2 to 11). Seventy-seven percent of participants discontinued the last BTK inhibitor for refractory or progressive disease. Pirtobrutinib was administered orally at 200 mg once daily and was continued until disease progression or unacceptable toxicity.

Society and culture

Legal status

In April 2023, 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 Jaypirca, intended for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The applicant for this medicinal product is Eli Lilly Nederland B.V.[14] Pirtobrutinib was approved for medical use in the European Union in November 2023.[1]

Further reading

External links

Notes and References

  1. Web site: Jaypirca EPAR . European Medicines Agency (EMA) . 20 November 2023 . 22 November 2023 . 22 November 2023 . https://web.archive.org/web/20231122061321/https://www.ema.europa.eu/en/medicines/human/EPAR/jaypirca . live .
  2. Web site: Jaypirca Product information . Union Register of medicinal products . 31 October 2023 . 22 November 2023 . 22 November 2023 . https://web.archive.org/web/20231122061342/https://ec.europa.eu/health/documents/community-register/html/h1738.htm . live .
  3. Web site: 27 January 2023 . FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma . FDA . 28 January 2023 . 28 January 2023 . https://web.archive.org/web/20230128215042/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-relapsed-or-refractory-mantle-cell-lymphoma . live .
  4. Aslan B, Kismali G, Iles LR, Manyam GC, Ayres ML, Chen LS, Gagea M, Bertilaccio MT, Wierda WG, Gandhi V . Pirtobrutinib inhibits wild-type and mutant Bruton's tyrosine kinase-mediated signaling in chronic lymphocytic leukemia . Blood Cancer Journal . 12 . 5 . 80 . May 2022 . 35595730 . 9123190 . 10.1038/s41408-022-00675-9 .
  5. U.S. FDA Approves Jaypirca (pirtobrutinib), the First and Only Non-Covalent (Reversible) BTK Inhibitor, for Adult Patients with Relapsed or Refractory Mantle Cell Lymphoma After at Least Two Lines of Systemic Therapy, Including a BTK Inhibitor . Eli Lilly . PR Newswire . 27 January 2023 . 31 January 2023 . 30 January 2023 . https://web.archive.org/web/20230130174121/https://www.prnewswire.com/news-releases/us-fda-approves-jaypirca-pirtobrutinib-the-first-and-only-non-covalent-reversible-btk-inhibitor-for-adult-patients-with-relapsed-or-refractory-mantle-cell-lymphoma-after-at-least-two-lines-of-systemic-therapy-including-a-301732669.html . live .
  6. Keam SJ . Pirtobrutinib: First Approval . Drugs . 83 . 6 . 547–553 . April 2023 . 37004673 . 10.1007/s40265-023-01860-1 . 257912433 . 19 November 2023 . 19 November 2023 . https://web.archive.org/web/20231119074857/https://figshare.com/articles/online_resource/Pirtobrutinib_First_Approval/22229662 . live .
  7. Telaraja D, Kasamon YL, Collazo JS, Leong R, Wang K, Li P, Dahmane E, Yang Y, Earp J, Grimstein M, Rodriguez LR, Theoret MR, Gormley NJ . FDA Approval Summary: Pirtobrutinib for Relapsed or Refractory Mantle Cell Lymphoma . Clinical Cancer Research . 30. 1. August 2023 . OF1–OF6 . 37624619 . 10.1158/1078-0432.CCR-23-1272 . 10841293 . 265965744 .
  8. Web site: Jaypirca- pirtobrutinib tablet, coated . DailyMed . 27 January 2023 . 11 February 2023 . 11 February 2023 . https://web.archive.org/web/20230211050627/https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=bd551845-0878-49a4-860f-839b83f6b801 . live .
  9. De SK . Pirtobrutinib: First Non-covalent Tyrosine Kinase Inhibitor for Treating Relapsed or Refractory Mantle Cell Lymphoma in Adults . Current Medicinal Chemistry . 31. October 2023 . 37818564 . 10.2174/0109298673251030231004052822 . 263828536 .
  10. Web site: FDA grants accelerated approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma . U.S. Food and Drug Administration (FDA) . 1 December 2023 . 3 December 2023 . 3 December 2023 . https://web.archive.org/web/20231203055242/https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic . live .
  11. Eli Lilly . Jaypirca (pirtobrutinib) Now Approved by U.S. FDA for the Treatment of Adult Patients with Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma Who Have Received at Least Two Lines of Therapy, Including a BTK Inhibitor and a BCL-2 Inhibitor . PR Newswire . 1 December 2023 . 3 December 2023 . 3 December 2023 . https://web.archive.org/web/20231203052947/https://www.prnewswire.com/news-releases/jaypirca-pirtobrutinib-now-approved-by-us-fda-for-the-treatment-of-adult-patients-with-chronic-lymphocytic-leukemia-or-small-lymphocytic-lymphoma-who-have-received-at-least-two-lines-of-therapy-including-a-btk-inhibitor-and--302003695.html . live .
  12. News: 27 January 2023. FDA approves Eli Lilly's drug for rare blood cancer. Reuters. 28 January 2023. https://web.archive.org/web/20230128041815/https://www.reuters.com/business/healthcare-pharmaceuticals/fda-approves-eli-lillys-blood-cancer-drug-2023-01-27/. live.
  13. Web site: Drug Trials Snapshots: Jaypirca . U.S. Food and Drug Administration (FDA) . 27 January 2023 . 13 May 2024.
  14. Web site: Jaypirca: Pending EC decision . European Medicines Agency . 26 April 2023 . 27 April 2023 . 26 April 2023 . https://web.archive.org/web/20230426204931/https://www.ema.europa.eu/en/medicines/human/summaries-opinion/jaypirca . live . Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.

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