Pirtobrutinib (Jaypirca)
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Mechanism of action
From the NCI Drug Dictionary: An orally available, selective, non-covalent Bruton’s tyrosine kinase (BTK) inhibitor with potential antineoplastic activity. Upon oral administration, BTK inhibitor LOXO-305 selectively and reversibly binds to BTK. This prevents both the activation of the B-cell antigen receptor (BCR) signaling pathway and BTK-mediated activation of downstream survival pathways, thereby inhibiting the growth of malignant B cells that overexpress BTK. Reversible binding of LOXO-305 may preserve antitumor activity in the presence of certain acquired resistance mutations, including C481 mutated BTK, and limit toxicity associated with inhibition of other non-BTK kinases.
Diseases for which it is used
Mechanisms of resistance
- Wang E, Mi X, Thompson MC, Montoya S, Notti RQ, Afaghani J, Durham BH, Penson A, Witkowski MT, Lu SX, Bourcier J, Hogg SJ, Erickson C, Cui D, Cho H, Singer M, Totiger TM, Chaudhry S, Geyer M, Alencar A, Linley AJ, Palomba ML, Coombs CC, Park JH, Zelenetz A, Roeker L, Rosendahl M, Tsai DE, Ebata K, Brandhuber B, Hyman DM, Aifantis I, Mato A, Taylor J, Abdel-Wahab O. Mechanisms of Resistance to Noncovalent Bruton's Tyrosine Kinase Inhibitors. N Engl J Med. 2022 Feb 24;386(8):735-743. link to original article link to PMC article PubMed
History of changes in FDA indication
- 2023-01-27: Granted accelerated approval for relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. (Based on BRUINMCL)
- 2023-12-01: Granted accelerated approval for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. (Based on BRUINCLL)
History of changes in EMA indication
- 2023-04-26: CHMP recommends conditional authorization as Jaypirca. Jaypirca as monotherapy would be indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) who have been previously treated with a Bruton’s tyrosine kinase (BTK) inhibitor.
Also known as
- Code name: LOXO-305
- Brand name: Jaypirca