Overview
Pirtobrutinib is a small molecule and a highly selective non-covalent inhibitor of Bruton’s tyrosine kinase (BTK). Its high selectivity has been associated with lower discontinuation rates due to adverse events and a lower incidence of atrial fibrillation. Unlike BTK covalent inhibitors, such as ibrutinib, that bind to the cysteine 481 (Cys481) amino acid within the active site of BTK, the inhibitory activity of pirtobrutinib is maintained even in the presence of Cys481 mutations. Although the mechanisms of resistance to covalent BTK inhibitors have not been fully elucidated, it appears that the presence of Cys481 mutations is the most common reason for resistance to covalent BTK inhibitors. However, other mutations may confer resistance to non-covalent BTK inhibitors such as pirtobrutinib. In January 2023, the use of pirtobrutinib for the treatment of relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy was approved under the FDA's Accelerated Approval pathway.
Background
Pirtobrutinib is a small molecule and a highly selective non-covalent inhibitor of Bruton’s tyrosine kinase (BTK). Its high selectivity has been associated with lower discontinuation rates due to adverse events and a lower incidence of atrial fibrillation. Unlike BTK covalent inhibitors, such as ibrutinib, that bind to the cysteine 481 (Cys481) amino acid within the active site of BTK, the inhibitory activity of pirtobrutinib is maintained even in the presence of Cys481 mutations. Although the mechanisms of resistance to covalent BTK inhibitors have not been fully elucidated, it appears that the presence of Cys481 mutations is the most common reason for resistance to covalent BTK inhibitors. However, other mutations may confer resistance to non-covalent BTK inhibitors such as pirtobrutinib. In January 2023, the use of pirtobrutinib for the treatment of relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy was approved under the FDA's Accelerated Approval pathway.
Indication
Pirtobrutinib is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.
Associated Conditions
- Refractory Mantle Cell Lymphoma
- Relapsed Mantle Cell Lymphoma
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/05/15 | Phase 3 | Not yet recruiting | |||
2025/05/13 | Phase 2 | Not yet recruiting | |||
2025/04/29 | Phase 2 | Not yet recruiting | |||
2025/03/14 | Phase 4 | Recruiting | |||
2025/03/14 | Phase 4 | Recruiting | |||
2025/02/21 | Phase 2 | Withdrawn | |||
2025/02/06 | Phase 2 | Recruiting | Peter MacCallum Cancer Centre, Australia | ||
2025/06/23 | Phase 1/2 | Not yet recruiting | |||
2024/09/19 | Phase 2 | Recruiting | |||
2024/08/14 | Phase 2 | Recruiting |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Eli Lilly and Company | 0002-7026 | ORAL | 100 mg in 1 1 | 12/20/2023 | |
| Eli Lilly and Company | 0002-6902 | ORAL | 50 mg in 1 1 | 12/20/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 10/30/2023 | ||
Authorised | 10/30/2023 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No HSA approvals found for this drug. | |||||
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| Pirtobrutinib Tablets | 国药准字HJ20240116 | 化学药品 | 片剂 | 10/22/2024 | |
| Pirtobrutinib Tablets | 国药准字HJ20240117 | 化学药品 | 片剂 | 10/22/2024 |
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| No TGA approvals found for this drug. | |||||