Table 1 Synopsis of clinical trials evaluating momelotinib and the anemia benefits it elicited in MF patients

A phase 1/2, open-label, dose-escalation study evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of orally-administered CYT387^a in PMF, post-PV MF or post-ET MF

NCT00935987

Core study

1/2

166 intermediate- and high-risk MF patients

Of 41 anemia-evaluable patients:

70% (23/30) became transfusion-independent by IWG-MRT criteria (2006)

Median duration of transfusion-independence: 9.6 months

11/2009–04/2012

[92]

An open-label phase 2 extension study evaluating the long term safety, tolerability, and efficacy of orally-administered CYT387^a in PMF, post-PV MF or post-ET MF

NCT01236638

Extension of the core study NCT00935987

Extension of core phase 1/2 study

120 intermediate- and high-risk MF patients

Of 111 anemia-evaluable patients:

75% (54/72) and 68% became transfusion-independent (for ≥ 8 weeks) at 8 and 12 weeks, respectively;

28% (11/39) of the patients with Hb < 10 g/dL had a median increase of 2.4 g/dL at 8 and 12 weeks

Median duration of 8-week anemia response: 7.7 months

11/2010–06/2014

[93]

Seven-year follow-up study of 100 patients with PMF, post-PV MF or post-ET MF, treated with CYT387^a  in a phase 1/2 clinical trial

NCT00935987 (part of the larger phase 1/2 trial with the same study identifier)

7-year follow-up of the phase 1/2 trial

100 intermediate- and high-risk MF patients treated at the Mayo Clinic

51% of the patients became transfusion-independent, and 44% of the patients had improvement in anemia

7 years

[94]

A phase 1/2, open-label study evaluating twice-daily administration of CYT387^a in PMF, post-PV MF or post-ET MF

NCT01423058

1/2

61 intermediate- and high-risk MF patients

Of 29 transfusion-dependent patients at baseline, 51.7% (15) achieved transfusion-independence for ≥ 8 weeks;

27% (3/11) transfusion independent patients had a Hb increase of ≥ 2 g/dL for ≥ 8 weeks

08/2011–06/2014

[89]

A phase 2, open-label, translational biology study of momelotinib in transfusion-dependent subjects with PMF, post-PV MF or post-ET MF

NCT02515630

2

41 transfusion-dependent MF patients

41% (17/41) of the patients became transfusion-independent^b

78% (21/27) of the transfusion-dependent patients had ≥ 50% decrease in RBC transfusion requirements for ≥ 8 weeks

49% transfusion-independence response rate at any time during the study in the evaluable population after ≥ 12 weeks of follow-up

01/2016–08/2017

Extension study:

04/2014–12/2018

[67]

SIMPLIFY-1: A phase 3, randomized, double-blind active-controlled study evaluating momelotinib versus ruxolitinib in subjects with PMF, post-PV MF or post-ET MF

NCT01969838

3

Randomization period: 24 weeks

432 JAK inhibitor-naïve patients who had high-risk, intermediate-2 risk or symptomatic intermediate-1 risk MF and platelet counts

 ≥ 50 × 10⁹/L

At week 24:

66.5% of the patients in the momelotinib arm became transfusion-independent^c versus 49.3% in the ruxolitinib arm (at baseline, 24.7% and 24% were transfusion-dependent, respectively)

83% of the patients treated with momelotinib required ≤ 4 units of RBCs versus 62% on ruxolitinib

Median RBC transfusion rate was 0 units/month with momelotinib versus 0.4 units/month with ruxolitinib

At week 48: 75% of the patients treated with momelotinib only became transfusion-independent versus 67% of the patients who were in the ruxolitinib arm and crossed over to momelotinib

Odds of remaining transfusion-independent were 9.3 times higher for momelotinib-treated patients versus ruxolitinib-treated patients

Median duration of transfusion-independence was not reached with momelotinib after follow-up of ≥ 3 years

12/2013–05/2019

Extension study: 05/2018 (onset)

Ongoing^f

[91, 95, 98]

SIMPLIFY-2: A phase 3, randomized study to evaluate the efficacy of momelotinib versus BAT in anemic or thrombocytopenic subjects with PMF, post-PV MF or post-ET MF who were treated with ruxolitinib

NCT02101268

3

Randomization period: 24 weeks

156 anemic or thrombocytopenic patients with MF, post-PV MF or post-ET MF previously treated with ruxolitinib^d

104 patients received momelotinib, and 52 patients received BAT (89% ruxolitinib);

56% (58/104) and 52% (27/52) were transfusion-dependent in the momelotinib and BAT/ruxolitinib arm, respectively; no platelet count was set

At week 24:

43% (45/104) of the patients treated with momelotinib became transfusion-independent^c versus 21% (11/52) in the BAT/ruxolitinib arm

Median RBC transfusion rate was 0.5 units/month with momelotinib versus 1.2 units/month with BAT/ruxolitinib

At week 48: 55% of the patients treated with momelotinib from the onset became transfusion-independent versus 40% who were in the BAT/ruxolitinib arm and crossed over to momelotinib

During the entire treatment period:

40% (42/104) of the momelotinib-treated patients versus 27% (14/52) in the BAT/ruxolitinib cohort did not require RBC transfusions

Median duration of transfusion independence with momelotinib was > 1 year at any time during the study

06/2014–04/2019

Extension study: 05/2018 (onset)

Ongoing^f

[91, 96]

MOMENTUM: A randomized, double-blind phase 3 study of momelotinib versus danazol in symptomatic, anemic subjects with PMF, post-PV MF or post-ET MF, previously treated with JAK inhibitors^e

NCT04173494

3

Randomization period: 24 weeks

180 patients with MF, post-PV MF or  post-ET MF

Eligible patients were anemic (Hb < 10 g/dL) and symptomatic (TSS ≥10) at baseline (platelet count ≥ 25 x 10⁹/L); and patients had been previously exposed to an approved JAK inhibitor

Proportion of transfusion-independent^c patients at week 24; and cumulative transfusion burden and Hb improvement

RBC transfusions will be recorded at 4-week intervals until week 48 and up to the end of week 204 (open label treatment period)

02/2020

Ongoing

[90]