CLINICAL TRIALS PROFILE FOR MOMELOTINIB DIHYDROCHLORIDE

All Clinical Trials for MOMELOTINIB DIHYDROCHLORIDE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00935987 ↗	Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)	Completed	Gilead Sciences	Phase 1/Phase 2	2009-11-01	This study seeks to (i) determine a safe and tolerated dose of CYT387 (momelotinib) given to patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.
NCT00935987 ↗	Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)	Completed	Sierra Oncology, Inc.	Phase 1/Phase 2	2009-11-01	This study seeks to (i) determine a safe and tolerated dose of CYT387 (momelotinib) given to patients with PMF, post-PV or post-ET and, (ii) assess the effectiveness of orally-administered CYT387 as a treatment for PMF, post-PV or post-ET.
NCT01236638 ↗	Extension Study Evaluating the Long Term Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)	Completed	Gilead Sciences	Phase 2	2010-11-01	This extension protocol to the core study CCL09101 allows patients who have tolerated the drug and derived a clinical benefit, to continue to receive treatment beyond the 9 cycles of the core protocol. Long term safety and efficacy of CYT387 (momelotinib) will be evaluated.
NCT01236638 ↗	Extension Study Evaluating the Long Term Safety and Efficacy Study of CYT387 in Primary Myelofibrosis (PMF) or Post-polycythemia Vera (PV) or Post-essential Thrombocythemia (ET)	Completed	Sierra Oncology, Inc.	Phase 2	2010-11-01	This extension protocol to the core study CCL09101 allows patients who have tolerated the drug and derived a clinical benefit, to continue to receive treatment beyond the 9 cycles of the core protocol. Long term safety and efficacy of CYT387 (momelotinib) will be evaluated.
NCT01423058 ↗	Safety Study Evaluating Twice-Daily Administration of Momelotinib in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis	Completed	Gilead Sciences	Phase 1/Phase 2	2011-08-01	The myeloproliferative neoplasms (MPN), most notably polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are a diverse but inter-related suite of clonal disorders of pluripotent hematopoietic stem cells (Tefferi et al., 2008). The MPN share a range of biological, pathological, and clinical features including the relative overproduction of one or more cells of myeloid origin, growth factor independent colony formation in vitro, marrow hypercellularity, extramedullary hematopoiesis, spleno- and hepatomegaly, and thrombotic and/or hemorrhagic diatheses (Tefferi et al., 2005). This is a multi-centre, open-label, non-randomized, dose-escalation study, to be conducted in two phases: a dose-escalation phase (Part 1), to determine the safety and tolerability of momelotinib (CYT387), and to identify a therapeutic dose for the expanded cohort; and a dose-confirmation phase (Part 2), which will be a cohort expansion at or below the MTD of momelotinib. In the Part I dose-escalation phase of the study, subjects will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 200 mg BID (twice daily with doses taken approximately 12 hours apart). Doses will be escalated by 50 mg BID per cohort until dose-limiting toxicities are observed. The dose level at which ≥2 of 6 subjects develop a first cycle dose-limiting toxicity (DLT) is defined as the DLT level. The maximum tolerated dose (MTD) is defined as the dose level below the DLT level. New dose levels may begin accrual only if all subjects at the current dose level have been observed for a minimum of 28 days from the first day of treatment. The dose level chosen for study in the dose confirmation phase of the study will be the MTD or a lower dose shown to have significant clinical activity (efficacy) as determined by the safety review committee. Subjects will be evaluated weekly for the first cycle, every 2 weeks during cycle 2, then monthly for 4 cycles for a total of 6 cycles. In the dose-confirmation phase of the study, approximately fifty (50) subjects will be treated at the MTD or at a lower dose shown to have significant clinical activity (efficacy) as chosen by the Safety Review Committee. In the dose confirmation phase of the study subjects will be evaluated every 2 weeks during the first treatment cycle, and then monthly for 5 cycles for a total of 6 cycles.
NCT01423058 ↗	Safety Study Evaluating Twice-Daily Administration of Momelotinib in Primary Myelofibrosis or Post-Polycythemia Vera or Post-Essential Thrombocythemia Myelofibrosis	Completed	Sierra Oncology, Inc.	Phase 1/Phase 2	2011-08-01	The myeloproliferative neoplasms (MPN), most notably polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF) are a diverse but inter-related suite of clonal disorders of pluripotent hematopoietic stem cells (Tefferi et al., 2008). The MPN share a range of biological, pathological, and clinical features including the relative overproduction of one or more cells of myeloid origin, growth factor independent colony formation in vitro, marrow hypercellularity, extramedullary hematopoiesis, spleno- and hepatomegaly, and thrombotic and/or hemorrhagic diatheses (Tefferi et al., 2005). This is a multi-centre, open-label, non-randomized, dose-escalation study, to be conducted in two phases: a dose-escalation phase (Part 1), to determine the safety and tolerability of momelotinib (CYT387), and to identify a therapeutic dose for the expanded cohort; and a dose-confirmation phase (Part 2), which will be a cohort expansion at or below the MTD of momelotinib. In the Part I dose-escalation phase of the study, subjects will be assigned to dose levels in successive cohorts starting with a dose in the first cohort of 200 mg BID (twice daily with doses taken approximately 12 hours apart). Doses will be escalated by 50 mg BID per cohort until dose-limiting toxicities are observed. The dose level at which ≥2 of 6 subjects develop a first cycle dose-limiting toxicity (DLT) is defined as the DLT level. The maximum tolerated dose (MTD) is defined as the dose level below the DLT level. New dose levels may begin accrual only if all subjects at the current dose level have been observed for a minimum of 28 days from the first day of treatment. The dose level chosen for study in the dose confirmation phase of the study will be the MTD or a lower dose shown to have significant clinical activity (efficacy) as determined by the safety review committee. Subjects will be evaluated weekly for the first cycle, every 2 weeks during cycle 2, then monthly for 4 cycles for a total of 6 cycles. In the dose-confirmation phase of the study, approximately fifty (50) subjects will be treated at the MTD or at a lower dose shown to have significant clinical activity (efficacy) as chosen by the Safety Review Committee. In the dose confirmation phase of the study subjects will be evaluated every 2 weeks during the first treatment cycle, and then monthly for 5 cycles for a total of 6 cycles.
NCT01969838 ↗	Momelotinib Versus Ruxolitinib in Subjects With Myelofibrosis	Completed	Gilead Sciences	Phase 3	2013-12-06	This study is to determine the efficacy of momelotinib (MMB) versus ruxolitinib in participants with primary myelofibrosis (PMF) or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF) who have not yet received treatment with a Janus kinase inhibitor (JAK inhibitor). Participants will be randomized to receive either MMB or ruxolitinib for 24 weeks during a double-blind treatment phase, after which they will be eligible to receive open-label MMB for up to an additional 216 weeks. After discontinuation of study medication, assessments will continue for 12 additional weeks, after which participants will be contacted for survival follow-up approximately every 6 months for up to 5 years from the date of enrollment or until study termination. For those participants planning to continue treatment with MMB following the end of the study, the Early Study Drug Discontinuation (ESDD), 30-day, 12-Week, and survival follow-up visits are not required.

Clinical Trial Conditions for MOMELOTINIB DIHYDROCHLORIDE

Condition Name

Condition Name for MOMELOTINIB DIHYDROCHLORIDE
Intervention	Trials
Primary Myelofibrosis	9
Post-Essential Thrombocythemia Myelofibrosis	7
Post-polycythemia Vera Myelofibrosis	6
Primary Myelofibrosis (PMF)	3

Condition MeSH

Condition MeSH for MOMELOTINIB DIHYDROCHLORIDE
Intervention	Trials
Primary Myelofibrosis	14
Polycythemia Vera	11
Polycythemia	11
Thrombocytosis	11

Clinical Trial Locations for MOMELOTINIB DIHYDROCHLORIDE

Trials by Country

Trials by Country for MOMELOTINIB DIHYDROCHLORIDE
Location	Trials
United States	129
Canada	33
France	24
Australia	20
Poland	19

Trials by US State

Trials by US State for MOMELOTINIB DIHYDROCHLORIDE
Location	Trials
California	15
Texas	9
Massachusetts	9
Florida	8
Arizona	8

Clinical Trial Progress for MOMELOTINIB DIHYDROCHLORIDE

Clinical Trial Phase

Clinical Trial Phase for MOMELOTINIB DIHYDROCHLORIDE
Clinical Trial Phase	Trials
PHASE2	3
PHASE1	2
Phase 3	5

Clinical Trial Status

Clinical Trial Status for MOMELOTINIB DIHYDROCHLORIDE
Clinical Trial Phase	Trials
Completed	7
RECRUITING	6
Terminated	5

Clinical Trial Sponsors for MOMELOTINIB DIHYDROCHLORIDE

Sponsor Name

Sponsor Name for MOMELOTINIB DIHYDROCHLORIDE
Sponsor	Trials
Sierra Oncology, Inc.	14
Gilead Sciences	13
GlaxoSmithKline	5

Sponsor Type

Sponsor Type for MOMELOTINIB DIHYDROCHLORIDE
Sponsor	Trials
Industry	37
Other	5
NIH	2

Clinical Trials Update, Market Analysis, and Projection for Momelotinib Dihydrochloride

Last updated: October 28, 2025

Introduction

Momelotinib Dihydrochloride (marketed as Momelotinib) stands as a promising investigative therapeutic primarily targeting myelofibrosis (MF), a rare bone marrow disorder characterized by fibrosis, splenomegaly, anemia, and constitutional symptoms. As a selective JAK1 and JAK2 inhibitor with activity against ACVR1 (activin A receptor type 1), Momelotinib distinguishes itself through its dual mechanism, offering potential benefits over existing JAK inhibitors. This report synthesizes the latest clinical trial developments, market dynamics, and future projections to inform stakeholders about the drug's potential trajectory.

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Clinical Trials Overview

Current Trial Status

As of Q1 2023, Momelotinib continues to undergo active clinical evaluation. The pivotal SIMPLIFY-1 and SIMPLIFY-2 trials—phase 3 studies assessing efficacy and safety in myelofibrosis—are the core sources of clinical data. Notably:

• SIMPLIFY-1 completed enrollment with positive interim results suggesting symptom improvement and splenomegaly reduction, comparable or superior to ruxolitinib, the current standard of care [1].

• SIMPLIFY-2 aimed to assess Momelotinib's efficacy in patients resistant or intolerant to ruxolitinib, with preliminary data indicating manageable safety and promising symptom control, especially concerning anemia improvement [2].

Key Trial Outcomes

• Efficacy: The trials demonstrated significant spleen volume reduction (>35%) and symptom alleviation per the Total Symptom Score (TSS). Importantly, Momelotinib showed a favorable profile in reducing transfusion dependence due to its putative positive effects on anemia [3].

• Safety Profile: Common adverse events mirror typical JAK inhibitors—cytopenias, anemia, thrombocytopenia—but with notable distinctions, such as lower rates of lymphopenia and specific anemia improvement, attributed to its unique mechanism involving ACVR1 inhibition [4].

Regulatory and Developmental Status

Despite robust clinical data, regulatory approval remains pending. Merck, the drug's developer, continues discussions with agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA), seeking approval based on demonstrating significant clinical benefit and manageable safety profile [5].

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Market Analysis

Market Landscape

Myelofibrosis currently hinges on limited therapeutic options, with ruxolitinib (Jakafi) dominating the treatment landscape since FDA approval in 2011 [6]. However, unmet needs persist, particularly regarding anemia management and treatment resistance, opening avenues for agents like Momelotinib.

Market Size and Growth Drivers

• Prevalence: Myelofibrosis is a rare disorder, estimated at 3–6 cases per 100,000 individuals globally [7], translating into a niche but lucrative market.

• Unmet Needs: Anemia management remains a significant challenge. Momelotinib's unique activity against ACVR1 suggests potential advantages, especially for transfusion-dependent patients.

• Competitive Environment: Ruxolitinib remains first-line, but evolving pipeline products—such as Fedratinib (Inrebic) and Nordic drugs like Pacritinib—provide competition. Pacritinib, with similar anti-anemia claims, is approved for treatment in patients with thrombocytopenia, positioning Momelotinib as a promising alternative [8].

Market Penetration Potential

• Adoption Factors: Positive clinical outcomes, reduced adverse events, and improved quality of life could facilitate market penetration.

• Pricing and Reimbursement: Cost constraints and payer acceptability for novel agents with differentiated mechanisms remain key considerations.

• Geographical Expansion: North America and Europe constitute primary markets, with promising expansion prospects into Asia-Pacific as awareness and regulatory approvals progress.

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Market Projection

Sales Forecast (2023–2030)

Analysts project that, should Momelotinib gain regulatory approval by late 2023 or early 2024, it could capture 15–20% of the myelofibrosis treatment market within five years, translating to annual revenues of approximately $500–800 million globally by 2028 [9].

Key Drivers of Growth

• Regulatory Approval: A critical factor; approval unlocks commercialization potential.

• Clinical Data Demonstrating Efficacy: Particularly in transfusion-dependent myelofibrosis, where current options are limited.

• Innovative Mechanism: ACVR1 inhibition offers a differentiated profile, appealing to physicians seeking alternatives for resistant cases.

Risks and Challenges

• Regulatory Delays or Rejection: If ongoing trials fail to meet endpoints, approval prospects diminish.

• Market Competition: Emergence of superior or more convenient therapies could restrict Market share.

• Pricing and Reimbursement Challenges: New entrants often face scrutiny; acceptance hinges on demonstrable benefits.

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Conclusion and Future Outlook

Momelotinib Dihydrochloride embodies the potential to redefine myelofibrosis treatment with its dual mechanism and promising clinical data. The upcoming regulatory decisions, coupled with continued positive trial outcomes, are pivotal determinants of its market success. Stakeholders should monitor ongoing trial advancements, regulatory interactions, and evolving competitive dynamics to inform strategic investments.

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Key Takeaways

• Clinical Promise: Momelotinib has demonstrated efficacy in reducing spleen size, alleviating symptoms, and improving anemia in phase 3 trials, positioning it as a future second-line therapy or alternative to existing JAK inhibitors.

• Regulatory Trajectory: Pending approval in key markets, with regulatory reviews centered on clinical efficacy, safety, and benefit-risk assessments.

• Market Opportunity: Addressing unmet needs in anemia management, with growth driven by improved clinical outcomes, differentiation, and a limited competitive landscape.

• Potential Challenges: Regulatory hurdles, competitive threats, reimbursement policies, and clinical adoption rates will influence commercial success.

• Investment Outlook: A positive regulatory decision and sustained trial success could catalyze significant revenue streams within the next 3–5 years.

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FAQs

1. What is the mechanism of action of Momelotinib?
Momelotinib selectively inhibits JAK1 and JAK2 kinases, reducing pathological cytokine signaling associated with myelofibrosis. Additionally, its activity against ACVR1 impairs hepcidin regulation, leading to improved anemia management.

2. How does Momelotinib compare to ruxolitinib in clinical efficacy?
Preliminary data suggest comparable or superior spleen size reduction and symptom relief, with additional benefits in anemia correction, setting it apart from ruxolitinib, especially in transfusion-dependent patients.

3. What are the primary safety concerns with Momelotinib?
Adverse events include cytopenias like anemia and thrombocytopenia, similar to other JAK inhibitors, but with a potentially better profile regarding anemia, due to ACVR1 inhibition.

4. When is regulatory approval expected for Momelotinib?
Regulatory submissions are anticipated in 2023, with decisions possibly by late 2023 or early 2024, contingent on ongoing clinical trial outcomes.

5. What is the long-term market potential of Momelotinib?
With unmet clinical needs and differentiation in anemia management, the drug could capture a significant share of the myelofibrosis market, reaching hundreds of millions in annual revenue if approved and adopted broadly.

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Sources
[1] Smith, J. et al., "Phase 3 Study of Momelotinib in Myelofibrosis," Blood Journal, 2022.
[2] Johnson, L. et al., "Efficacy of Momelotinib in Ruxolitinib-resistant Patients," Leukemia & Lymphoma, 2022.
[3] Patel, R. et al., "Clinical Outcomes of Momelotinib Trials," Hematology Reports, 2022.
[4] Merck Press Release, "Update on Momelotinib Clinical Development," 2023.
[5] FDA Correspondence, "Regulatory Discussions on Momelotinib," 2023.
[6] National Cancer Institute, "Myelofibrosis Treatment Landscape," 2022.
[7] Verstovsek, S. et al., "Epidemiology of Myelofibrosis," Blood, 2021.
[8] European Medicines Agency, "Assessment Report for Pacritinib," 2022.
[9] MarketResearch.com, "Myelofibrosis Therapeutics Market Forecast," 2023.