Table 1.
Approved ACVR1 inhibitors and other ACVR1 inhibitors in clinical development for the treatment of anemia in MF patients.
| Agent | Study Phase | Indication | Inhibitory Effects |
|---|---|---|---|
| Pacritinib | Approved by the FDA based on the phase 3 PERSIST-2 trial (NCT02055781) | Adults with intermediate- or high-risk MF and platelet counts <50 × 109/L | Mean IC50 (ACVR1) = 16.7 nM [28] Inhibitor of JAK2, ACVR1, IRAK1, and FLT3 |
| Momelotinib | FDA-approved based on the phase 3 MOMENTUM (NCT04173494) and SIMPLIFY-1 (NCT01969838) trials | Adults with intermediate- or high-risk MF (primary or secondary) and anemia | Mean IC50 (ACVR1) = 52.5 nM [28] IC50 (ACVR1) = 8.4 nM [80] Inhibitor of JAK1/2 and ACVR1 |
| Jaktinib | Evaluated in a phase 3 trial in comparison to hydroxyurea (NCT04617028) | In clinical development for MF treatment | IC50 (ACVR1) values were not determined. JAK1/2/3 and ACVR1 inhibitor [91] |
| Zilurgisertib | Evaluated in a phase 1/2 trial as a monotherapy or in combination with ruxolitinib (NCT04455841) | In clinical development for MF treatment | IC50 (ACVR1) = 15 nM [94] ACVR1 inhibitor |
Abbreviations: ACVR1: activin receptor type I; FDA: Federal Drug Administration; FLT3: fms-like tyrosine kinase 3; IC50: half-maximal inhibitory concentration; JAK: Janus kinase; IRAK1: interleukin 1 receptor associated kinase 1; MF: myelofibrosis.