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	8
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	12
Polycythemia	11
Thrombocytosis	11
Thrombocythemia, Essential	11

Clinical Trial Locations for Momelotinib Dihydrochloride

Trials by Country

Trials by Country for Momelotinib Dihydrochloride
Location	Trials
United States	125
Canada	32
France	22
Australia	20
Poland	19

Trials by US State

Trials by US State for Momelotinib Dihydrochloride
Location	Trials
California	15
Massachusetts	8
Missouri	8
Texas	8
Florida	8

Clinical Trial Progress for Momelotinib Dihydrochloride

Clinical Trial Phase

Clinical Trial Phase for Momelotinib Dihydrochloride
Clinical Trial Phase	Trials
Phase 3	5
Phase 2	7
Phase 1/Phase 2	2

Clinical Trial Status

Clinical Trial Status for Momelotinib Dihydrochloride
Clinical Trial Phase	Trials
Completed	7
Terminated	5
Recruiting	3

Clinical Trial Sponsors for Momelotinib Dihydrochloride

Sponsor Name

Sponsor Name for Momelotinib Dihydrochloride
Sponsor	Trials
Sierra Oncology, Inc.	14
Gilead Sciences	13
Incyte Corporation	1

Sponsor Type

Sponsor Type for Momelotinib Dihydrochloride
Sponsor	Trials
Industry	32
NIH	2
Other	1

Momelotinib Dihydrochloride: A Comprehensive Update on Clinical Trials, Market Analysis, and Projections

Last updated: December 31, 2024

Introduction to Momelotinib Dihydrochloride

Momelotinib dihydrochloride, also known by its proprietary name Ojjaara, is a promising anti-cancer drug developed for the treatment of various forms of myelofibrosis. This drug acts as a Janus Kinase (JAK) 1/2 and Activin Receptor Type 1 (ACVR1) inhibitor, making it a unique candidate in the therapeutic landscape for myeloproliferative neoplasms (MPNs)[2][3][5].

Clinical Trials Overview

MOMENTUM Study

The MOMENTUM study is a pivotal clinical trial conducted by Sierra Oncology to evaluate the efficacy and safety of momelotinib in patients with intermediate or high-risk myelofibrosis who have previously been treated with an approved JAK inhibitor and are anemic with splenomegaly. This study aims to enroll patients who are no longer benefiting from their current JAK inhibitor therapy[3].

Key Findings from MOMENTUM

The MOMENTUM study has shown promising results, particularly in improving hemoglobin levels and reducing the need for transfusions in patients with myelofibrosis. The trial demonstrated that momelotinib can achieve significant efficacy endpoints, including the rate of no transfusion by week 24, which is a critical measure for patients with anemia[1].

Other Clinical Trials

In addition to the MOMENTUM study, momelotinib has been involved in various other clinical trials. These include Phase 2 and Phase 3 studies evaluating its efficacy in different subgroups of myelofibrosis patients, such as those with JAK2V617F or CALR mutations. These trials have generally shown positive outcomes, highlighting the drug's potential in treating myelofibrosis[4].

Regulatory Approval and Indications

FDA Approval

Momelotinib was approved by the FDA in 2023 for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis (PMF) and secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia) in adults with anemia. The approved dosage is 200 mg once daily[1].

Indications

The drug is indicated for patients with anemia, a common complication in myelofibrosis, and those who have failed or are intolerant to other JAK inhibitors. This approval expands the treatment options for patients with these conditions, offering a new therapeutic avenue[1][2].

Pharmacologic Activity and Mechanism of Action

JAK and ACVR1 Inhibition

Momelotinib's unique mechanism involves the inhibition of JAK 1/2 and ACVR1. This dual inhibition is crucial as it targets multiple pathways involved in the pathogenesis of myelofibrosis, potentially offering a more comprehensive therapeutic effect compared to JAK inhibitors alone[2][5].

Pharmacokinetics

The drug is administered orally as film-coated tablets, ensuring ease of use for patients. Its pharmacokinetic profile has been studied extensively, showing favorable absorption and distribution characteristics that support its once-daily dosing regimen[2].

Market Analysis and Projections

Market Potential

Given its approval and positive clinical trial results, momelotinib is poised to capture a significant share of the myelofibrosis treatment market. GlobalData's analysis suggests that the drug's unique profile and the lack of sufficient historical data for Phase III drugs in this indication could lead to a favorable market position[2].

Net Present Value (NPV) Model

GlobalData's NPV model for momelotinib dihydrochloride takes into account various factors including patent law, regulatory approval processes, and projected cash flows. This model helps in evaluating the drug's financial potential and identifying hidden opportunities in the market[5].

Patient Experience and Long-Term Use

Long-Term Extension Studies

Patients who participated in previous clinical trials and are still benefiting from momelotinib are being rolled over into long-term extension studies. Some patients have been receiving momelotinib for up to 8 years, indicating its long-term safety and efficacy profile[3].

Patient Experience Data

The integrated review by the FDA includes patient experience data, which highlights the drug's impact on patients' quality of life. This data is crucial for understanding the real-world benefits of momelotinib beyond clinical trial settings[1].

Challenges and Considerations

Hepatotoxicity and Other Safety Concerns

While momelotinib has shown significant efficacy, it is not without safety concerns. The FDA review highlighted issues such as hepatotoxicity and an imbalance in COVID-19 infections and deaths in the momelotinib arm during the MOMENTUM trial. These risks are being closely monitored and managed[1].

Competitive Landscape

The myelofibrosis treatment market is competitive, with other JAK inhibitors like ruxolitinib already established. However, momelotinib's unique mechanism and its ability to address anemia in patients who have failed other treatments position it as a valuable addition to the therapeutic arsenal[2][4].

Key Takeaways

• Clinical Trials Success: Momelotinib has demonstrated significant efficacy in clinical trials, particularly in improving hemoglobin levels and reducing transfusion needs.
• Regulatory Approval: Approved by the FDA for the treatment of intermediate or high-risk myelofibrosis in adults with anemia.
• Unique Mechanism: Dual inhibition of JAK 1/2 and ACVR1 sets it apart from other JAK inhibitors.
• Market Potential: Poised to capture a significant market share due to its unique profile and favorable clinical data.
• Long-Term Safety: Patients have been receiving the drug for up to 8 years, indicating its long-term safety and efficacy.

FAQs

What is momelotinib dihydrochloride used for?

Momelotinib dihydrochloride (Ojjaara) is used for the treatment of intermediate or high-risk myelofibrosis, including primary myelofibrosis and secondary myelofibrosis, in adults with anemia.

Who developed momelotinib?

Momelotinib was initially developed by Gilead Sciences Inc. but was later acquired by Sierra Oncology in 2018 for continued development.

What is the dosage of momelotinib?

The approved dosage of momelotinib is 200 mg once daily, administered orally.

What are the unique features of momelotinib?

Momelotinib is a dual inhibitor of JAK 1/2 and ACVR1, which sets it apart from other JAK inhibitors. It also has a favorable pharmacokinetic profile and is effective in patients who have failed other JAK inhibitors.

Are there any safety concerns associated with momelotinib?

Yes, there are safety concerns such as hepatotoxicity and an imbalance in COVID-19 infections and deaths observed in clinical trials. These risks are being closely monitored.

Sources

1. FDA Integrated Review: "216873Orig1s000 INTEGRATED REVIEW - accessdata.fda.gov"
2. Pharmaceutical Technology: "Momelotinib dihydrochloride by GSK for Chronic Idiopathic Myelofibrosis"
3. MPN Research Foundation: "UPDATE ON PROMISING MF TREATMENT, MOMELOTINIB"
4. Patsnap: "Momelotinib Dihydrochloride - Drug Targets, Indications, Patents"
5. GlobalData: "Net Present Value Model: Momelotinib Dihydrochloride"