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.

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
Missouri	8
Florida	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

Last updated: July 28, 2026

Momelotinib Dihydrochloride clinical trials update, market forecast, and IP timeline

Momelotinib dihydrochloride is an oral JAK1/JAK2 inhibitor with ACVR1 (activin A receptor type 1) signaling suppression, being developed for myelofibrosis (MF) including primary MF and post–polycythemia vera (post-PV) and post–essential thrombocythemia (post-ET) MF. The near-term commercial outlook is shaped by (1) continued differentiation versus other MF therapies on anemia outcomes, (2) evidence durability in ongoing Phase 3 programs and longer-term follow-up, and (3) safety and label expansion in transfusion-dependent populations. IP and exclusivity positioning is central to generic entry timing and biosimilar is not applicable (small molecule).

What is momelotinib dihydrochloride and what indications are in clinical trials?

Answer: Momelotinib dihydrochloride targets JAK/STAT and ACVR1 pathways to improve splenomegaly and symptoms in MF and to address anemia and transfusion burden via hepcidin-related mechanisms.

Core clinical programs by disease setting

Key clinical efforts focus on:

• Primary MF and secondary MF (post-PV, post-ET)
• Transfusion-dependent anemia (TDA) subsets
• Comparative endpoints including spleen response, symptom response, and transfusion independence

Key comparators in the MF market

Momelotinib’s competitive set includes:

• Ruxolitinib (JAK inhibitor)
• Fedratinib (JAK2-selective)
• Pacritinib (JAK2/IRAK-like pathway with favorable platelet profile)
• Other emerging agents targeting fibrosis or novel pathways, depending on emerging late-stage data

How are ongoing and completed momelotinib clinical trials progressing?

Answer: The most decision-relevant evidence comes from Phase 3 trials designed around myelofibrosis response and anemia/transfusion outcomes, with results driving potential label expansions and payer uptake.

Phase 3 evidence themes that drive adoption

Across MF, trial readouts that influence prescribing include:

• Durability of spleen volume reduction (e.g., proportion achieving ≥35% reduction from baseline)
• Symptom improvement (MF-related symptom burden scales)
• Transfusion independence rates and time to first transfusion
• Hemoglobin change trajectories
• Safety tolerability profile for chronic use

What endpoints matter for transfusion-dependent MF

In TDA subpopulations, the commercial impact of momelotinib depends on:

• Rate of sustained transfusion independence
• Durability across multiple assessment cycles
• Ability to maintain response while managing neutropenia or other cytopenias
• Reduced need for erythropoiesis-stimulating agents (where used)

What is the latest clinical trials update for momelotinib dihydrochloride?

Answer: Latest updates in MF typically consist of (1) long-term follow-up from Phase 3 pivotal trials, (2) subgroup analyses for anemia and transfusion outcomes, and (3) ongoing enrollment or dose optimization work in additional MF settings.

Where updates usually show up

• Press releases and investor presentations tied to clinical milestones
• Conference abstracts (EHA, ASH, ISH)
• Regulatory submissions for label expansion based on trial endpoints

Market-relevant question: is efficacy durable enough for line-of-therapy shift?

If longer-term data show maintained spleen and symptom responses while improving anemia and reducing transfusions, momelotinib can shift earlier in treatment selection, raising market penetration.

How does momelotinib compare with ruxolitinib, fedratinib, and pacritinib for myelofibrosis?

Answer: Momelotinib’s positioning relies on anemia and transfusion benefit differentiation while maintaining MF response metrics comparable to or competitive with other JAK inhibitors, with safety tailored to chronic use.

Competitive comparison framework

• Efficacy (spleen and symptoms): compares the proportion meeting major spleen reduction and symptom-response thresholds
• Anemia/transfusion outcomes: compares transfusion independence and hemoglobin trajectories
• Safety/tolerability: compares anemia-related adverse events, cytopenias, and dose modifications
• Patient fit: differentiates by baseline anemia severity and transfusion dependence

Implication for payer and formulary

Transfusion reduction can improve total cost of care, not just drug spend, which can accelerate formulary placement in managed care settings where transfusion is a high-cost component.

When does momelotinib dihydrochloride lose exclusivity and what does that mean for generic entry?

Answer: Exclusivity timing is driven by the drug’s composition-of-matter and follow-on patents plus regulatory exclusivities tied to approval and manufacturing data protections. Generic entry risk scales with remaining patent life and whether Orange Book-listed patents cover dosage form and method-of-use.

How to map exclusivity to generic risk

Generic launch exposure typically falls into three buckets:

1. Composition-of-matter expiry: strongest determinant if no blocking formulation/method patents remain.
2. Formulation and polymorph protection: can block therapeutically equivalent generics.
3. Method-of-use coverage: can delay label-based competition by constraining carve-outs.

Paragraph IV and settlement dynamics

For MF indications, any Paragraph IV challenge strength will depend on:

• Whether Orange Book patents are listed for the specific approved strengths/dosage form
• Whether method-of-use patents are asserted in relevant jurisdictions
• Settlement terms that govern “at-risk” launch timing

What is the Orange Book status of momelotinib dihydrochloride and which patents are listed?

Answer: Orange Book status and listed patents determine the practical shelf-life of generics. Patent numbers and specific expiration dates drive litigation and entry timing.

Orange Book coverage categories to extract

• Drug substance (composition of matter)
• Drug product (formulation, polymorph, salt form)
• Use (method-of-treatment claims tied to MF populations)

(No Orange Book listing details are included here because the necessary patent-by-patent dataset is not provided in the request context.)

What patent estate strength does momelotinib dihydrochloride have for MF?

Answer: Patent estate strength for momelotinib is assessed by counting active, unexpired patents across substance, formulation, and method-of-use categories and by the likelihood that at least one blocking patent survives common challenges.

How patent strength translates to commercial timelines

• Strong estate: fewer viable generic pathways, slower market erosion
• Narrow estate: earlier biosimilar/generic substitution-like effects (not biosimilar here) via cost competitiveness

How does momelotinib’s market access profile affect sales growth and adoption?

Answer: Adoption in MF is influenced by label positioning, evidence in transfusion-dependent populations, and payer preference for therapies that reduce transfusion resource utilization.

Key commercial drivers in MF

• Treatment-line movement (earlier versus later line)
• Managed care formularies that reward anemia/transfusion reduction
• Real-world tolerability leading to sustained dosing and lower discontinuation

What is the current market size for myelofibrosis and how much share could momelotinib capture?

Answer: Momelotinib’s share depends on its ability to win:

• TDA segments where clinicians seek anemia benefit
• Patients intolerant or less responsive to competing JAK inhibitors
• Settings where transfusion reduction improves overall cost profiles

(No quantified market-size baselines are provided because a numeric market dataset and region/time horizon are not included in the request context.)

What revenue projection scenarios are most plausible for momelotinib through patent-relevant horizons?

Answer: Revenue projections should be modeled in three scenarios based on label penetration, competitor responses, and exclusivity constraints.

Scenario model structure

• Base case: steady share gains driven by transfusion/transplant-adjacent clinician preferences, limited by tolerability and sequencing with other JAK inhibitors
• Upside: rapid uptake if trials show sustained transfusion independence and payers accept cost offsets from reduced transfusions
• Downside: slower share if durability or safety restricts dosing or if competitors demonstrate superior anemia control

What inputs dominate the model

• Penetration rate in primary MF and post-PV/post-ET cohorts
• Conversion rate from relapsed/refractory versus earlier lines
• Persistence (time on drug) and dose reductions
• Market competition and formulary restrictions by region

What manufacturing and formulation risks could constrain supply or IP defensibility?

Answer: Supply constraints in oral oncology are less common than in injectables, but manufacturing scale-up and polymorph/formulation control can affect defensibility and launch readiness.

Key technical/IP friction points

• Salt form control and solid-state form patents
• Impurity profiles and process validation for generic replication
• Stability and bioavailability considerations for different strengths

What generic entry risks exist for momelotinib dihydrochloride?

Answer: The highest risk areas are earliest-expiring composition-of-matter patents and gaps where formulation/method-of-use patents do not block therapeutic equivalence.

Risks that determine “at-risk” launch probability

• Whether a Paragraph IV petitioner can design around formulation/method-of-use claims
• Whether Orange Book-listed patents are enforceable and not withdrawn
• Whether settlements include market-entry moratoria

What momelotinib dihydrochloride litigation affects market timing?

Answer: Patent litigation and settlements determine whether generic entrants can launch on the earliest legally permitted date or whether delay agreements shift entry.

Litigation types to map

• Hatch-Waxman Paragraph IV suits in federal district courts
• ITC-related assertions (rare for small-molecule generics but possible)
• Settlement agreements that impose standstill or carve-outs

(No specific case list is provided because litigation dockets and asserted patent numbers are not included in the request context.)

Key Takeaways

• Momelotinib’s commercial thesis in myelofibrosis is anchored on anemia and transfusion outcomes in addition to spleen and symptom efficacy.
• Clinical trial updates that matter commercially are long-term follow-up and subgroup durability in transfusion-dependent populations.
• Market share and revenue projection hinge on sequencing, payer acceptance of transfusion-cost offsets, and persistence/tolerability in chronic use.
• Exclusivity and Orange Book-listed patents control generic entry risk and the timing of any Paragraph IV challenges; the practical risk depends on composition-of-matter versus formulation/method-of-use coverage.
• Patent litigation and settlements can materially shift generic launch dates away from bare expiration.

FAQs

1. What endpoints drive payer coverage decisions for momelotinib in myelofibrosis?
2. How does transfusion independence in momelotinib trials influence sequencing versus ruxolitinib or fedratinib?
3. Which myelofibrosis subgroups (primary MF vs post-PV vs post-ET) most impact momelotinib’s commercial penetration?
4. What types of patents (composition, formulation, method-of-use) most commonly block generic entry for JAK inhibitors in MF?
5. How do settlement terms in Paragraph IV cases typically affect the launch calendar for oral oncology small molecules?

References

1. FDA. Orange Book: Approved Drug Products with Therapeutic Equivalence Evaluations. U.S. Food and Drug Administration.
2. ClinicalTrials.gov. Studies of momelotinib dihydrochloride in myelofibrosis. U.S. National Library of Medicine.
3. Company investor presentations and conference abstracts for momelotinib myelofibrosis trials.