MF drug-development pipeline
| Drug (class) . | Efficacy . | Comments . | Ref. . |
|---|---|---|---|
| JAK inhibitors | |||
| Momelotinib (JAK1/JAK2 inhibitor) | SIMPLIFY 1 • Spleen response 26.5% • Symptom response 29% • Greater rate of transfusion independence as compared with ruxolitinib | Ongoing phase 3 momentum study in second line for MF and symptoms/anemia (NCT04173494) | 42 |
| Pacritinib (JAK2/FLT3 inhibitor) | PERSIST 1 • Spleen response 25% (including 33% response in those with platelets <50 × 109/L) • Symptom response 36% rate | Ongoing phase 3 study PACIFICA41 (NCT03165734) | 39 |
| NS-018 (JAK2 inhibitor) | Phase 1 • Dose escalation completed | Ongoing phase 2 study for prior JAK2 inhibitor failures (NCT01423851) | 44 |
| Ruxolitinib combination studies | |||
| Luspatercept* (receptor type IIb and IgG1Fc domain) | Greater efficacy for anemia in combination with ruxolitinib than single agent (57% in nontransfusion dependent/53% in transfusion dependent) | Ongoing trial NCT03194542 | 45 |
| CPI-0610* (BET inhibitor) | Ongoing study active alone or in combination with ruxolitinib as second line; active in combination with ruxolitinib in front line | Ongoing trial NCT02158858 | 46 |
| Navitoclax* (Bcl-2 inhibitor) | Ongoing study, when added to suboptimal ruxolitinib responders’ responses seen for splenomegaly and symptoms | Ongoing trial NCT03222609 | 47 |
| Pomalidomide (IMID) | Ongoing study anemia responses seen when added to ruxolitinib | Ongoing trial NCT01644110 | 48 |
| Thalidomide (IMID) | Ongoing study responses seen in anemia and/or thrombocytopenia when added to ruxolitinib | Ongoing trial NCT03069326 | 49 |
| PU-H71 (HSP90 inhibitor) | Ongoing phase 1b study in MF patients on stable dose of ruxolitinib | Ongoing trial NCT03935555 | N/A |
| Single-agent alternative pathway inhibitors | |||
| AVID 200 (inhibits TGFβ 1/3) | Ongoing phase 1 | Ongoing trial NCT03895112 | N/A |
| Bomedemstat (IMG-7289; LSD1 inhibitor) | Ongoing phase 1 | Ongoing trial NCT03136185 | 51 |
| Imetelstat (telomerase inhibitor) | 27% response rate Responses more likely if JAK2-V617F mutated or ASXL1 mutated | Completed trial NCT02426086 | 50 |
| LCL161 (SMAC mimetic) | Ongoing phase 2 | Ongoing trial NCT02098161 | 52 |
| Tagraxofusp (SL-401; CD123 targeting) | Ongoing phase 1/2 | Ongoing trial NCT02268253 | 53 |
| Drug (class) . | Efficacy . | Comments . | Ref. . |
|---|---|---|---|
| JAK inhibitors | |||
| Momelotinib (JAK1/JAK2 inhibitor) | SIMPLIFY 1 • Spleen response 26.5% • Symptom response 29% • Greater rate of transfusion independence as compared with ruxolitinib | Ongoing phase 3 momentum study in second line for MF and symptoms/anemia (NCT04173494) | 42 |
| Pacritinib (JAK2/FLT3 inhibitor) | PERSIST 1 • Spleen response 25% (including 33% response in those with platelets <50 × 109/L) • Symptom response 36% rate | Ongoing phase 3 study PACIFICA41 (NCT03165734) | 39 |
| NS-018 (JAK2 inhibitor) | Phase 1 • Dose escalation completed | Ongoing phase 2 study for prior JAK2 inhibitor failures (NCT01423851) | 44 |
| Ruxolitinib combination studies | |||
| Luspatercept* (receptor type IIb and IgG1Fc domain) | Greater efficacy for anemia in combination with ruxolitinib than single agent (57% in nontransfusion dependent/53% in transfusion dependent) | Ongoing trial NCT03194542 | 45 |
| CPI-0610* (BET inhibitor) | Ongoing study active alone or in combination with ruxolitinib as second line; active in combination with ruxolitinib in front line | Ongoing trial NCT02158858 | 46 |
| Navitoclax* (Bcl-2 inhibitor) | Ongoing study, when added to suboptimal ruxolitinib responders’ responses seen for splenomegaly and symptoms | Ongoing trial NCT03222609 | 47 |
| Pomalidomide (IMID) | Ongoing study anemia responses seen when added to ruxolitinib | Ongoing trial NCT01644110 | 48 |
| Thalidomide (IMID) | Ongoing study responses seen in anemia and/or thrombocytopenia when added to ruxolitinib | Ongoing trial NCT03069326 | 49 |
| PU-H71 (HSP90 inhibitor) | Ongoing phase 1b study in MF patients on stable dose of ruxolitinib | Ongoing trial NCT03935555 | N/A |
| Single-agent alternative pathway inhibitors | |||
| AVID 200 (inhibits TGFβ 1/3) | Ongoing phase 1 | Ongoing trial NCT03895112 | N/A |
| Bomedemstat (IMG-7289; LSD1 inhibitor) | Ongoing phase 1 | Ongoing trial NCT03136185 | 51 |
| Imetelstat (telomerase inhibitor) | 27% response rate Responses more likely if JAK2-V617F mutated or ASXL1 mutated | Completed trial NCT02426086 | 50 |
| LCL161 (SMAC mimetic) | Ongoing phase 2 | Ongoing trial NCT02098161 | 52 |
| Tagraxofusp (SL-401; CD123 targeting) | Ongoing phase 1/2 | Ongoing trial NCT02268253 | 53 |
Spleen responses: 35% volume reduction. Symptom responses: 50% reduction in MFSAF or Myeloproliferative Neoplasms Symptom Assessment Form (MPNSAF) total symptoms.
Bcl-2, B-cell lymphoma 2; BET, bromodomain and extraterminal domain; HSP90, heat shock protein 90; IgG1, immunoglobulin G1; IMID, immunomodulatory imide; N/A, not applicable; Ref., reference; SMAC, second mitochondrial activator of caspases.
These trials have both single-agent and combination arms (with ruxolitinib).