|Main uses||Mantle cell lymphoma (MCL)|
|Side effects||Tiredness, musculoskeletal pain, diarrhea, swelling, shortness of breath, pneumonia, bruising|
|Typical dose||200 mg OD|
|Chemical and physical data|
|Molar mass||479.436 g·mol−1|
|3D model (JSmol)|
Pirtobrutinib, sold under the brand name Jaypirca, is a medication used to treat mantle cell lymphoma (MCL). It is used when other treatments fail. It is taken by mouth.
Common side effects include tiredness, musculoskeletal pain, diarrhea, swelling, shortness of breath, pneumonia, and bruising. Laboratory abnormalities may include low neutrophils, low lymphocytes, or low platelets. Other side effects may include atrial fibrillation and other cancers. Use in pregnancy may harm the baby. It works to inhibit lymphocytes by blocking Bruton's tyrosine kinase (BTK).
Pirtobrutinib was approved for medical use in the United States in 2023. In Europe conditional approval was recommended in 2013. In the United States it costs about 22,000 USD per month as of 2023.
In the US, 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.
It is generally taken at a dose of 200 mg once per day.
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.
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.
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 participants with MCL previously treated with a BTK inhibitor. Participants had a median of three prior lines of therapy, with 93% having two or more prior lines. The most common prior BTK inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% had discontinued their last BTK inhibitor due to refractory or progressive disease.
Society and culture
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, intended for the treatment of relapsed or refractory mantle cell lymphoma (MCL). The applicant for this medicinal product is Eli Lilly Nederland B.V.
- ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 "Jaypirca- pirtobrutinib tablet, coated". DailyMed. 27 January 2023. Archived from the original on 11 February 2023. Retrieved 11 February 2023.
- ↑ 2.0 2.1 Aslan B, Kismali G, Iles LR, Manyam GC, Ayres ML, Chen LS, et al. (May 2022). "Pirtobrutinib inhibits wild-type and mutant Bruton's tyrosine kinase-mediated signaling in chronic lymphocytic leukemia". Blood Cancer Journal. 12 (5): 80. doi:10.1038/s41408-022-00675-9. ISSN 2044-5385. PMC 9123190. PMID 35595730.
- ↑ "Jaypirca: Pending EC decision". European Medicines Agency. 26 April 2023. Archived from the original on 26 April 2023. Retrieved 12 May 2023.
- ↑ "Pirtobrutinib". Retrieved 12 May 2023.
- ↑ "FDA approves Eli Lilly's drug for rare blood cancer". Reuters. 27 January 2023. Archived from the original on 2023-01-28.
- ↑ 6.0 6.1 6.2 "FDA grants accelerated approval to pirtobrutinib for relapsed or refractory mantle cell lymphoma". FDA. 2023-01-27. Archived from the original on 2023-01-28. Retrieved 2023-01-28. This article incorporates text from this source, which is in the public domain.
- ↑ 7.0 7.1 "Jaypirca: Pending EC decision". European Medicines Agency. 26 April 2023. Archived from the original on 26 April 2023. Retrieved 27 April 2023. Text was copied from this source which is copyright European Medicines Agency. Reproduction is authorized provided the source is acknowledged.
- Cohen JB, Shah NN, Alencar AJ, Gerson JN, Patel MR, Fakhri B, et al. (October 2022). "MCL-133 Pirtobrutinib, a Highly Selective, Non-Covalent (Reversible) BTK Inhibitor in Previously Treated Mantle Cell Lymphoma: Updated Results From the Phase 1/2 BRUIN Study". Clinical Lymphoma, Myeloma & Leukemia. 22 Suppl 2: S394–S395. doi:10.1016/S2152-2650(22)01569-5. PMID 36164120.
- Eyre TA, Shah NN, Dreyling M, Jurczak W, Wang Y, Cheah CY, et al. (November 2022). "BRUIN MCL-321: phase III study of pirtobrutinib versus investigator choice of BTK inhibitor in BTK inhibitor naïve mantle cell lymphoma". Future Oncology. 18 (36): 3961–3969. doi:10.2217/fon-2022-0976. PMID 36377973.
- Mato AR, Shah NN, Jurczak W, Cheah CY, Pagel JM, Woyach JA, et al. (March 2021). "Pirtobrutinib in relapsed or refractory B-cell malignancies (BRUIN): a phase 1/2 study". Lancet. 397 (10277): 892–901. doi:10.1016/S0140-6736(21)00224-5. PMID 33676628. S2CID 232116910.
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