Table 1.
Selected drugs targeting the MPN microenvironment.
| Drug | Target (Mechanism) |
Condition(s) | Trial (Phase) |
Reference | Results/Comments |
|---|---|---|---|---|---|
| PRM-151 | Recombinant human pentraxin-2 | MF |
NCT01981850 (Phase II) |
Verstovsek et al., 2019 [157] |
↓fibrosis, ↓transfusions, only modest SI |
| Fresolimumab (GC1008) | TGF-β (MoAb) |
MF |
NCT01291784 (Phase I) |
Mascarenhas et al., 2014 [167] |
Only 3 patients enrolled; early termination |
|
Sotatercept
(ACE-011) |
TGF-β (ligand trap) |
MF with anemia |
NCT01712308 (Phase II) |
Bose et al., 2016 [164] |
±ruxolitinibEndpoint: ↑Hb ORR (monotherapy) = 35% |
|
Luspatercept
(ACE-536) |
TGF-β (ligand trap) |
MF with anemia |
NCT03194542 (Phase II) |
Gerds et al., 2019 [165] |
±ruxolitinibEndpoint: ↑Hb ORR (monotherapy) = 20% |
| AVID200 | TGF-β1/β3 (ligand trap) |
MF |
NCT03895112 (Phase I/Ib) |
Still recruiting; no results published yet |
|
| Galunisertib (LY2157299) | ALK5 (kinase inhibitor) |
MF | Preclinical | Yue et al., 2017 [168] |
Murine models only: ↓fibrosis |
| Alisertib (MLN8237) | AURKA (kinase inhibitor) |
MF (or AMKL) |
NCT02530619 (Phase I) |
Gangat et al., 2019 [153] |
SVR = 29%, TI = 8%, SI = 23%, ↓fibrosis |
|
Bomedemstat
(IMG-7289) |
LSD1 (small molecule inhibitor) | MF |
NCT03136185 (Phase II) |
Pettit et al., 2019 [156] |
Still recruiting; interim results: SI, slight SVR in a subset of patients |
| Mirabegron | β-3 adrenergic agonist | JAK2V617F+ MPNs |
NCT02311569 (Phase II) |
Drexler et al., 2019 [170] |
↑nestin + MSCs, mild ↓fibrosis, ↓MK clusters, ↔ JAK2V617F allele burden |
|
Simtuzumab
(GS-6624) |
LOXL2 (MoAb) |
MF |
NCT01369498 (Phase II) |
Verstovsek et al., 2017 [174] |
±ruxolitinib ↓Fibrosis in 36.7%; limited overall efficacy |
| GANT61 | Gli1/Hedgehog (small molecule inhibitor) | MF | Preclinical | Schneider et al., 2017 [88] |
Murine and human in vitro models: ↓fibrosis, ↓myofibroblastic phenotype |
MF: primary or post-essential thrombocythemia/polycythemia vera myelofibrosis; MoAb: monoclonal antibody; SVR: spleen volume reduction; SI: symptom improvement; Hb: hemoglobin; ORR: overall response rate; TI: transfusion independence; MK: megakaryocyte; AMKL: acute megakaryoblastic leukemia; ALK5: TGF-β receptor I kinase; AURKA: Aurora kinase A; LSD1: lysine-specific histone demethylase 1; LOXL2: lysyl oxidase-like 2; ↓: decrease; ↑: increase; ↔: no effects; ±: with or without; %: percentage of patients.