Loading
MANIFEST-2 found that adding the BET inhibitor pelabresib to ruxolitinib shrank spleens in nearly twice as many people with myelofibrosis, but the improvement in symptoms did not reach statistical significance, leaving the drug's approval uncertain.
BET proteins read the epigenetic marks that drive the inflammatory and fibrotic programme of myelofibrosis. MANIFEST-2 randomised 430 patients with myelofibrosis who had not yet received a JAK inhibitor to ruxolitinib with pelabresib or with placebo. The primary endpoint was a spleen volume reduction of 35 percent or more at week 24; the key secondary endpoint was a 50 percent or greater fall in total symptom score.
The combination roughly doubled the spleen response rate, meeting the primary endpoint, and showed improvements in bone marrow fibrosis and anaemia, but the symptom endpoint favoured the combination without reaching statistical significance. Regulators asked for more data, and the drug had not been approved by the time of writing.
Numbers are from the trial as recorded here; see the source links in the table below. This is orientation, not medical advice: ask your team how closely the trial population matches you.
430 enrolled.
Difference 30.4% (95% CI 21.6 to 39.3)
SourceDifference 6.0% (95% CI -3.5 to 15.5)
SourceDifference -1.94 (95% CI -3.92 to 0.04)
Source| Endpoint | Arm | n | Value | HR (95% CI) | p | Source |
|---|---|---|---|---|---|---|
| Spleen volume reduction >=35% at week 24primary | Pelabresib + ruxolitinib | 214 | 65.9% | - | <0.001 | link |
| Placebo + ruxolitinib | 216 | 35.2% | ||||
| Total symptom score reduction >=50% at week 24 (TSS50) | Pelabresib + ruxolitinib | 214 | 52.3% | - | - | link |
| Placebo + ruxolitinib | 216 | 46.3% | ||||
| Absolute change in total symptom score at week 24 | Pelabresib + ruxolitinib | 214 | -15.99 points | - | 0.0545 | link |
| Placebo + ruxolitinib | 216 | -14.05 points | ||||
| Grade 3 or higher anaemia | Pelabresib + ruxolitinib | 214 | 23.1% | - | - | link |
| Placebo + ruxolitinib | 216 | 36.5% | ||||
| Grade 3 or higher thrombocytopenia | Pelabresib + ruxolitinib | 214 | 13.2% | - | - | link |
| Placebo + ruxolitinib | 216 | 6.1% |
Shares Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis) and the tag subtype-trials.
Shares Novartis and the tag subtype-trials.
Shares Pelabresib, Novartis.
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis), Novartis.
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).
Shares Ruxolitinib, Primary myelofibrosis, Myeloproliferative neoplasms (PV, ET, myelofibrosis).