CLINICAL TRIALS PROFILE FOR FEDRATINIB HYDROCHLORIDE

All Clinical Trials for Fedratinib Hydrochloride

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT03165734 ↗	A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis	Recruiting	Covance	Phase 3	2017-06-26	This study (study ID PAC203 North America; PAC303 ex-North America) is evaluating 200 mg BID of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia (platelet count <50,000/μL). Approximately 348 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 232 patients) or to P/C therapy (approximately 116 patients) Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/ Post-essential Thrombocythemia Myelofibrosis Intervention/treatment: Drug-Pacritinib
NCT03165734 ↗	A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis	Recruiting	PSI CRO	Phase 3	2017-06-26	This study (study ID PAC203 North America; PAC303 ex-North America) is evaluating 200 mg BID of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia (platelet count <50,000/μL). Approximately 348 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 232 patients) or to P/C therapy (approximately 116 patients) Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/ Post-essential Thrombocythemia Myelofibrosis Intervention/treatment: Drug-Pacritinib
NCT03165734 ↗	A Phase 3 Study of Pacritinib in Patients With Primary Myelofibrosis, Post Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis	Recruiting	CTI BioPharma	Phase 3	2017-06-26	This study (study ID PAC203 North America; PAC303 ex-North America) is evaluating 200 mg BID of pacritinib compared to physician's choice (P/C) therapy in patients with MF and severe thrombocytopenia (platelet count <50,000/μL). Approximately 348 patients in total will be enrolled, randomized 2:1 to either pacritinib (approximately 232 patients) or to P/C therapy (approximately 116 patients) Condition or disease: Primary Myelofibrosis/Post-Polycythemia Vera Myelofibrosis/ Post-essential Thrombocythemia Myelofibrosis Intervention/treatment: Drug-Pacritinib
NCT03755518 ↗	A Safety Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib With Concomitant Lusp	Recruiting	Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation	Phase 3	2019-03-27	This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib including a Sub-study with concomitant Luspatercept for subjects with anemia. The primary objective of the main study is to evaluate the percentage of subjects with at least a 35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of fedratinib. The primary objective of the sub-study is to evaluate the safety and tolerability of Luspatercept when administered concomitantly with Fedratinib.
NCT03755518 ↗	A Safety Trial of Fedratinib in Subjects With DIPSS, Intermediate or High-Risk Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocythemia Myelofibrosis and Previously Treated With Ruxolitinib With Concomitant Lusp	Recruiting	Celgene	Phase 3	2019-03-27	This is Single-Arm, Open-Label Efficacy and Safety Trial of Fedratinib in Subjects with DIPSS (Dynamic International Prognostic Scoring System)-Intermediate or High- Risk Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (post-PV MF), or Post-Essential Thrombocythemia Myelofibrosis (post-ET MF) and Previously Treated with Ruxolitinib including a Sub-study with concomitant Luspatercept for subjects with anemia. The primary objective of the main study is to evaluate the percentage of subjects with at least a 35% reduction in spleen size and one of the secondary objectives is to evaluate the safety of fedratinib. The primary objective of the sub-study is to evaluate the safety and tolerability of Luspatercept when administered concomitantly with Fedratinib.
NCT03952039 ↗	An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previousl	Recruiting	Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation	Phase 3	2019-09-09	A Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy (BAT) in subjects with DIPSS (Dynamic International Prognostic Scoring System)-intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with ruxolitinib. The primary objective of the study is to evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms.
NCT03952039 ↗	An Efficacy and Safety Study of Fedratinib Compared to Best Available Therapy in Subjects With DIPSS-intermediate or High-risk Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, or Post-essential Thrombocythemia Myelofibrosis and Previousl	Recruiting	Celgene	Phase 3	2019-09-09	A Phase 3, multicenter, open-label, randomized study to evaluate the efficacy and safety of fedratinib compared to best available therapy (BAT) in subjects with DIPSS (Dynamic International Prognostic Scoring System)-intermediate or high-risk primary myelofibrosis (PMF), post-polycythemia vera myelofibrosis (post-PV MF), or post-essential thrombocythemia myelofibrosis (post-ET MF) and previously treated with ruxolitinib. The primary objective of the study is to evaluate the percentage of subjects with at least 35% spleen volume reduction in the fedratinib and the BAT arms.

Clinical Trial Conditions for Fedratinib Hydrochloride

Condition Name

Condition Name for Fedratinib Hydrochloride
Intervention	Trials
Primary Myelofibrosis	7
Myelofibrosis	7
Healthy Volunteers	5
Myeloproliferative Neoplasm	5

Condition MeSH

Condition MeSH for Fedratinib Hydrochloride
Intervention	Trials
Primary Myelofibrosis	12
Polycythemia Vera	7
Polycythemia	7
Thrombocytosis	7

Clinical Trial Locations for Fedratinib Hydrochloride

Trials by Country

Trials by Country for Fedratinib Hydrochloride
Location	Trials
United States	74
Australia	10
Canada	9
Italy	5
Spain	5

Trials by US State

Trials by US State for Fedratinib Hydrochloride
Location	Trials
Texas	9
Florida	6
New Jersey	5
New York	4
Missouri	4

Clinical Trial Progress for Fedratinib Hydrochloride

Clinical Trial Phase

Clinical Trial Phase for Fedratinib Hydrochloride
Clinical Trial Phase	Trials
Phase 3	3
Phase 2	6
Phase 1/Phase 2	3

Clinical Trial Status

Clinical Trial Status for Fedratinib Hydrochloride
Clinical Trial Phase	Trials
Recruiting	15
Not yet recruiting	6
Completed	2

Clinical Trial Sponsors for Fedratinib Hydrochloride

Sponsor Name

Sponsor Name for Fedratinib Hydrochloride
Sponsor	Trials
Celgene	7
Impact Biomedicines, Inc., a wholly owned subsidiary of Celgene Corporation	6
Bristol-Myers Squibb	5

Sponsor Type

Sponsor Type for Fedratinib Hydrochloride
Sponsor	Trials
Industry	28
Other	8
NIH	2

Fedratinib Hydrochloride: Clinical Trials Update, Market Analysis, and Projections

Introduction

Fedratinib hydrochloride, marketed as Inrebic, is a significant advancement in the treatment of myelofibrosis, a type of bone marrow disorder. This oral kinase inhibitor targets the Janus kinase 2 (JAK2) and FMS-like tyrosine kinase 3 (FLT3) pathways, offering a promising option for patients who have failed or are intolerant to other treatments like ruxolitinib.

Mechanism of Action

Fedratinib inhibits JAK2, JAK1, JAK3, and TYK2, with the highest potency against JAK2, both in its wild-type and mutationally activated forms. It also inhibits FLT3, which is crucial in certain myeloproliferative diseases. By blocking the phosphorylation of STAT proteins, fedratinib reduces cell proliferation and induces apoptotic cell death, thereby alleviating symptoms associated with myelofibrosis[2][5].

Clinical Trials Update

FREEDOM2 Trial

The FREEDOM2 trial, a multicenter, open-label, randomized, controlled phase 3 study, evaluated the efficacy and safety of fedratinib in patients with intermediate-2 or high-risk myelofibrosis who were previously treated with ruxolitinib. The trial demonstrated that 36% of patients receiving fedratinib achieved a spleen volume reduction (SVR) of at least 35% at the end of cycle 6, compared to 6% in the best available therapy (BAT) group. This trial highlighted the effectiveness of fedratinib as a second-line treatment option and showed strategies for managing gastrointestinal adverse events and low thiamine levels[3].

FREEDOM Trial

The FREEDOM trial, another phase 3b study, focused on patients with intermediate- or high-risk myelofibrosis and a platelet count of ≥50 × 10^9/L, who had previously been treated with ruxolitinib. Despite being cut short due to COVID-19, the trial showed that 25.7% of patients achieved the primary endpoint of ≥35% SVR at the end of cycle 6, and 62.9% showed a best overall response of ≥35% SVR up to the end of treatment. This study also demonstrated effective mitigation of gastrointestinal adverse events[4].

Ongoing and Planned Trials

Several ongoing trials are exploring the use of fedratinib in various settings:

• A study at the H. Lee Moffitt Cancer Center and Research Institute is investigating fedratinib in myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic neutrophilic leukemia (CNL), with a trial completion date projected for April 2026[1].
• A post-marketing surveillance study in Korean patients with myelofibrosis is ongoing, with a completion date set for December 2029[1].
• Other trials are examining the use of fedratinib in combination therapies and as a maintenance treatment to prevent post-transplant relapse in myeloproliferative neoplasms[1].

Safety and Adverse Events

Fedratinib has been associated with several adverse events, including gastrointestinal issues, anemia, thrombocytopenia, and low thiamine levels. However, studies have shown that these can be effectively managed through prophylactic measures such as antiemetics, thiamine supplementation, and monitoring. The FREEDOM2 trial reported that gastrointestinal adverse events were mostly grade 1-2 in severity and decreased over time, and no cases of encephalopathy were observed in the FREEDOM trial[3][4].

Market Analysis

Current Market Position

Fedratinib has established itself as a viable second-line treatment for myelofibrosis, particularly for patients who have failed or are intolerant to ruxolitinib. Its approval by regulatory bodies, including the FDA, has opened up a significant market segment.

Competitive Landscape

The market for myelofibrosis treatments is competitive, with ruxolitinib (Jakafi) being the primary first-line treatment. However, fedratinib's efficacy in patients who have failed or are intolerant to ruxolitinib positions it as a strong second-line option. Other drugs like momelotinib (Ojjaara) are also in the pipeline, but fedratinib's unique mechanism of action and clinical trial data make it a compelling choice[3][4].

Market Projections

Given the positive outcomes from clinical trials and the growing need for effective treatments in myelofibrosis, fedratinib is projected to capture a significant share of the market. The drug's ability to reduce spleen size and alleviate symptoms, combined with effective strategies for managing adverse events, will likely drive its adoption. As more data from ongoing trials becomes available, fedratinib's market position is expected to strengthen.

Regulatory Status

Fedratinib was approved by the FDA in 2019 after a complex development history that included a clinical hold due to safety concerns such as Wernicke’s encephalopathy and heart failure. However, these issues were addressed, and the drug was ultimately approved for use in patients with intermediate-2 or high-risk myelofibrosis[2].

Dosage and Administration

The recommended dose of fedratinib is 400 mg daily, as established by clinical trials and regulatory reviews. This dose has been shown to be effective in reducing spleen volume and alleviating symptoms without significant additional benefits from higher doses[5].

Patient Impact

For patients with myelofibrosis, fedratinib offers a new hope, especially those who have exhausted other treatment options. The drug's ability to reduce spleen size and improve symptom scores significantly enhances the quality of life for these patients.

"Findings from FREEDOM2 support fedratinib as a second-line Janus kinase inhibitor option to reduce spleen size after ruxolitinib failure or intolerance in patients with myelofibrosis, and shows effective strategies for management of gastrointestinal adverse events and low thiamine concentrations through prophylaxis, monitoring, and treatment."[3]

Conclusion

Fedratinib hydrochloride is a critical addition to the therapeutic arsenal for myelofibrosis, offering a potent and effective treatment option for patients who have failed or are intolerant to first-line treatments. With its strong clinical trial data, effective management of adverse events, and regulatory approval, fedratinib is poised to make a significant impact in the market.

Key Takeaways

• Efficacy: Fedratinib is effective in reducing spleen size and alleviating symptoms in patients with myelofibrosis who have failed or are intolerant to ruxolitinib.
• Safety: The drug is associated with gastrointestinal adverse events, anemia, and thrombocytopenia, but these can be managed effectively.
• Market Position: Fedratinib is a strong second-line treatment option in a competitive market.
• Regulatory Status: Approved by the FDA in 2019 after addressing initial safety concerns.
• Dosage: Recommended dose is 400 mg daily.
• Patient Impact: Significantly improves quality of life for patients with myelofibrosis.

FAQs

What is fedratinib hydrochloride used for?

Fedratinib hydrochloride is used for the treatment of intermediate-2 or high-risk myelofibrosis in patients who have failed or are intolerant to ruxolitinib.

What are the common adverse events associated with fedratinib?

Common adverse events include gastrointestinal issues, anemia, thrombocytopenia, and low thiamine levels.

How is fedratinib administered?

Fedratinib is administered orally at a recommended dose of 400 mg daily.

What is the current market position of fedratinib?

Fedratinib is a strong second-line treatment option for myelofibrosis, particularly for patients who have failed or are intolerant to ruxolitinib.

Are there ongoing clinical trials for fedratinib?

Yes, several ongoing trials are exploring the use of fedratinib in various settings, including combination therapies and post-transplant maintenance.

What is the projected market growth for fedratinib?

Given its positive clinical trial outcomes and effective management of adverse events, fedratinib is projected to capture a significant share of the myelofibrosis treatment market.

Sources

1. LARVOL VERI: News - Inrebic (fedratinib) - LARVOL VERI
2. FDA: Multi-Discipline Review - accessdata.fda.gov
3. PubMed: Efficacy and safety of fedratinib in patients with myelofibrosis ...
4. PubMed: Safety and efficacy of fedratinib in patients with myelofibrosis ...
5. Health Canada: Summary Basis of Decision for Inrebic