Summary of selected drugs approved or in clinical development for MPNs
| MF . | Mechanism . | Trial . | Clinical response . |
|---|---|---|---|
| Rux57,58 (approved) | JAK2 inhibitor | 3 | SVR35 = 42% TSS50 = 50% |
| Fedratinib79 (approved) | JAK2 inhibitor | 3 Rux naïve | SVR35 = 37% TSS50 = 40% |
| 2 Prior rux | SVR35 = 55% TSS50 = 26% | ||
| Pacritinib61 (approved) | JAK2 inhibitor | 3 Prior rux allowed Platelets <100 × 109/L | SVR35 = 29% TSS50 = 32% |
| Momelitinib67 | JAK2 inhibitor | 3 Rux naïve | SVR35 = 27% TSS50 = 38% Transfusion independence at wk 24 in 67% |
| AVID20080 | TGF-β trap | 1B (N = 21) Prior rux | SVR35 = 19% TSS50 = 43% 3/4 patients treated to cycle 12 with clinical improvement |
| Bomedemstat81 | LSD1 inhibitor | 1/2 (N = 89) Prior rux | SVR35 = 37% TSS50 = 39% BM fibrosis improvement in 17% |
| Imetelstat82 | Telomerase inhibitor | 2 (N = 59) Prior rux | SVR35 = 10% TSS50 = 32% BM fibrosis improvement in 40.5% |
| Navtemadlin83 | MDM2 inhibitor | 2 (N = 32∗) Prior rux | SVR35 = 16% TSS50 = 30% BM fibrosis improvement in 27% |
| Navitoclax + rux84 | BCL2 inhibitor | 2 (N = 34) | SVR35 = 27% TSS50 = 30% Anemia response in 64% BM fibrosis improvement in 33% |
| Parsaclisib + rux85 | PI3K inhibitor | 2 (N = 51) | SVR35 = 27% TSS50 = 50% |
| Pelabresib86 | BET inhibitor | 2 (N = 86) | SVR35 = 11% TSS50 = 28% TD to TI conversion rate in 16% BM fibrosis improvement in 23.4% |
| Pelabresib + rux87 | BET inhibitor | 2 (N = 78) Rux naïve | SVR35 = 67% TSS50 = 57% BM fibrosis improvement in 33% |
| 2 (N = 70) Prior rux | SVR35 = 21% TSS50 = 53% TD to TI conversion rate 36% | ||
| Selinexor88 | Selective inhibitor of nuclear export | 2 (N = 10) | SVR35 = 30% Reduction in TSS in 8 evaluable patients |
| Tagraxofusp89 | CD123 (IL-3Rα) targeted therapy (recombinant human IL-3 fused to diphtheria toxin) | 1/2 (N = 39) | SVR10 = 47%; SVR50 = 29% TSS50 = 36% |
| PV/ET | |||
| Pegylated interferon46,48 | Interferon | 3 | CHR: 35% at 1 y; 21% at 2 y MR: 16% at 18 mo |
| Ropeginterferon49 | Interferon | 3 | CHR: 43% at 1 y; 48% at 2 y; 54% at 3 and 4 y MR: 34% at 1 and 2 y; 50% at 3 and 4 y |
| Rusfertide90,91 | Hepcidin mimetic | 2 (N = 63) PV | Mean phlebotomy after enrollment: 0.43 (vs 4.63 prior) |
| Bomedemstat92 | LSD1 inhibitor | 2 (N = 29) ET | TSS50 = 53% 100% with normalization of platelet counts |
| MF . | Mechanism . | Trial . | Clinical response . |
|---|---|---|---|
| Rux57,58 (approved) | JAK2 inhibitor | 3 | SVR35 = 42% TSS50 = 50% |
| Fedratinib79 (approved) | JAK2 inhibitor | 3 Rux naïve | SVR35 = 37% TSS50 = 40% |
| 2 Prior rux | SVR35 = 55% TSS50 = 26% | ||
| Pacritinib61 (approved) | JAK2 inhibitor | 3 Prior rux allowed Platelets <100 × 109/L | SVR35 = 29% TSS50 = 32% |
| Momelitinib67 | JAK2 inhibitor | 3 Rux naïve | SVR35 = 27% TSS50 = 38% Transfusion independence at wk 24 in 67% |
| AVID20080 | TGF-β trap | 1B (N = 21) Prior rux | SVR35 = 19% TSS50 = 43% 3/4 patients treated to cycle 12 with clinical improvement |
| Bomedemstat81 | LSD1 inhibitor | 1/2 (N = 89) Prior rux | SVR35 = 37% TSS50 = 39% BM fibrosis improvement in 17% |
| Imetelstat82 | Telomerase inhibitor | 2 (N = 59) Prior rux | SVR35 = 10% TSS50 = 32% BM fibrosis improvement in 40.5% |
| Navtemadlin83 | MDM2 inhibitor | 2 (N = 32∗) Prior rux | SVR35 = 16% TSS50 = 30% BM fibrosis improvement in 27% |
| Navitoclax + rux84 | BCL2 inhibitor | 2 (N = 34) | SVR35 = 27% TSS50 = 30% Anemia response in 64% BM fibrosis improvement in 33% |
| Parsaclisib + rux85 | PI3K inhibitor | 2 (N = 51) | SVR35 = 27% TSS50 = 50% |
| Pelabresib86 | BET inhibitor | 2 (N = 86) | SVR35 = 11% TSS50 = 28% TD to TI conversion rate in 16% BM fibrosis improvement in 23.4% |
| Pelabresib + rux87 | BET inhibitor | 2 (N = 78) Rux naïve | SVR35 = 67% TSS50 = 57% BM fibrosis improvement in 33% |
| 2 (N = 70) Prior rux | SVR35 = 21% TSS50 = 53% TD to TI conversion rate 36% | ||
| Selinexor88 | Selective inhibitor of nuclear export | 2 (N = 10) | SVR35 = 30% Reduction in TSS in 8 evaluable patients |
| Tagraxofusp89 | CD123 (IL-3Rα) targeted therapy (recombinant human IL-3 fused to diphtheria toxin) | 1/2 (N = 39) | SVR10 = 47%; SVR50 = 29% TSS50 = 36% |
| PV/ET | |||
| Pegylated interferon46,48 | Interferon | 3 | CHR: 35% at 1 y; 21% at 2 y MR: 16% at 18 mo |
| Ropeginterferon49 | Interferon | 3 | CHR: 43% at 1 y; 48% at 2 y; 54% at 3 and 4 y MR: 34% at 1 and 2 y; 50% at 3 and 4 y |
| Rusfertide90,91 | Hepcidin mimetic | 2 (N = 63) PV | Mean phlebotomy after enrollment: 0.43 (vs 4.63 prior) |
| Bomedemstat92 | LSD1 inhibitor | 2 (N = 29) ET | TSS50 = 53% 100% with normalization of platelet counts |
CHR, complete hematologic response; IL-3, interleukin 3; IL-3Rα, interleukin 3 receptor α; MR, molecular response; rux, ruxolitinib; SVR10/35/50, spleen volume reduction by 10%/35%/50% (shown are observations at week 24); TD, transfusion dependence; TI, transfusion independence; TSS50, total symptom score improvement by 50%.
Sample size of cohort receiving dosing selected for phase 3 testing; response rates are reported for this cohort.