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Fedratinib

Fedratinib is a drug being studied in clinical trials for the treatment of myelofibrosis, a rare blood cancer that affects bone marrow function. These trials aim to evaluate the safety, effectiveness, and proper dosing of fedratinib in patients with various forms of myelofibrosis, including those who have previously been treated with other medications. The studies also examine how fedratinib interacts with other drugs and how it can be administered to patients with different health conditions.

Table of Contents

What is Fedratinib?

Fedratinib, also known by its brand name Inrebic[1], is a medication used to treat certain blood disorders. It is a potent and selective inhibitor of JAK2 kinase activity[2]. JAK2 is an enzyme that plays a crucial role in the production of blood cells. By inhibiting this enzyme, fedratinib can help control the abnormal growth of blood cells in certain conditions.

What Conditions Does Fedratinib Treat?

Fedratinib is primarily used to treat several types of myelofibrosis, which are rare blood cancers that affect the bone marrow. These include:

  • Primary Myelofibrosis (PMF): A condition where the bone marrow produces abnormal blood cells, leading to scarring of the bone marrow.
  • Post-Polycythemia Vera Myelofibrosis (Post-PV MF): A progression of polycythemia vera, a condition where the body produces too many red blood cells, into myelofibrosis.
  • Post-Essential Thrombocythemia Myelofibrosis (Post-ET MF): A progression of essential thrombocythemia, a condition where the body produces too many platelets, into myelofibrosis.

These conditions are typically classified as intermediate or high-risk based on the Dynamic International Prognostic Scoring System (DIPSS)[2][3]. Fedratinib is often used in patients who have previously been treated with another medication called ruxolitinib[2].

Additionally, research is ongoing to evaluate the effectiveness of fedratinib in treating other blood disorders such as myelodysplastic/myeloproliferative neoplasms (MDS/MPNs) and chronic neutrophilic leukemia (CNL)[1].

How Does Fedratinib Work?

Fedratinib works by targeting and inhibiting an enzyme called JAK2 (Janus Associated Kinase 2). This enzyme is involved in signaling pathways that control the production of blood cells. In myelofibrosis and related conditions, JAK2 is often overactive, leading to the overproduction of abnormal blood cells and scarring of the bone marrow.

By inhibiting JAK2, fedratinib can help to:

  • Reduce the size of an enlarged spleen, a common symptom in myelofibrosis
  • Alleviate symptoms associated with myelofibrosis, such as fatigue, night sweats, and abdominal discomfort
  • Potentially slow the progression of the disease

How is Fedratinib Administered?

Fedratinib is taken orally, usually once daily. The typical dose is 400 mg per day, which is usually given as four 100 mg capsules[2][1]. It’s generally recommended to take fedratinib with food, preferably during an evening meal, at approximately the same time each day[4].

In some cases, the dose may be adjusted based on individual patient factors or if certain side effects occur. Always take fedratinib exactly as prescribed by your healthcare provider.

Efficacy of Fedratinib

Clinical trials have shown promising results for fedratinib in treating myelofibrosis. The main measures of efficacy include:

  • Spleen Volume Reduction (SVR): Many patients experience a significant reduction in spleen size. In clinical trials, the goal was often to achieve at least a 35% reduction in spleen volume[2].
  • Symptom Improvement: Fedratinib has been shown to reduce the total symptom score (TSS) in many patients. This is typically measured using a tool called the Myelofibrosis Symptom Assessment Form (MFSAF)[3].
  • Duration of Response: Studies have also looked at how long the positive effects of fedratinib last[3].

It’s important to note that the response to fedratinib can vary from person to person. Your healthcare provider will monitor your response to the treatment and adjust as necessary.

Safety Profile and Side Effects

Like all medications, fedratinib can cause side effects. Some of the most common side effects observed in clinical trials include:

  • Gastrointestinal issues: Such as nausea, diarrhea, and vomiting[3]
  • Changes in blood cell counts: Including anemia (low red blood cell count) and thrombocytopenia (low platelet count)[2]
  • Liver enzyme abnormalities[2]
  • Fatigue

In rare cases, a serious condition called Wernicke’s encephalopathy has been reported. This is a neurological emergency caused by thiamine (vitamin B1) deficiency. Symptoms can include confusion, vision changes, and difficulty with coordination[3].

To monitor for potential side effects, your healthcare provider will likely perform regular blood tests and check your thiamine levels while you’re taking fedratinib[2].

Ongoing Research and Future Directions

Research on fedratinib is ongoing, with several clinical trials currently in progress. These studies aim to:

  • Further evaluate the long-term safety and efficacy of fedratinib in myelofibrosis patients[3]
  • Investigate its potential use in other blood disorders, such as MDS/MPNs and CNL[1]
  • Study the effects of fedratinib in different patient populations, including those with varying degrees of liver impairment[5]
  • Assess the real-world effectiveness of fedratinib outside of clinical trial settings[6]

These ongoing studies will help to refine our understanding of fedratinib and potentially expand its use to benefit more patients with blood disorders.

Aspect Details
Drug Name Fedratinib
Primary Conditions Studied Primary Myelofibrosis, Post-polycythemia Vera Myelofibrosis, Post-essential Thrombocythemia Myelofibrosis
Main Mechanism JAK2 inhibitor
Key Outcomes Measured Spleen volume reduction, symptom improvement, safety profile, pharmacokinetics
Common Dosages in Trials 300-400 mg daily
Special Populations Studied Patients with hepatic impairment, previously treated with ruxolitinib
Notable Side Effects Monitored Gastrointestinal events, changes in blood counts, Wernicke’s encephalopathy
Drug Interactions Studied With CYP2C19 and CYP3A4 inhibitors (e.g., fluconazole)

FAQ

  • What is fedratinib? Fedratinib is a medication that works by inhibiting a protein called JAK2, which is involved in the development of myelofibrosis. It is being studied as a potential treatment for various forms of myelofibrosis, including primary myelofibrosis, post-polycythemia vera myelofibrosis, and post-essential thrombocythemia myelofibrosis.
  • What are the main goals of the clinical trials involving fedratinib? The main goals of these trials are to assess the safety and effectiveness of fedratinib in treating myelofibrosis, determine the appropriate dosage, evaluate its effects on spleen size and symptom reduction, and understand how it interacts with other medications or health conditions.
  • Who can participate in fedratinib clinical trials? Participants in fedratinib trials typically include adults with various forms of myelofibrosis, such as primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Some trials focus on patients who have previously been treated with other medications like ruxolitinib, while others may include newly diagnosed patients or those with specific health conditions.
  • What are some of the outcomes measured in fedratinib clinical trials? Common outcomes measured in these trials include spleen volume reduction, symptom improvement (using standardized symptom assessment tools), changes in blood cell counts, adverse events, and quality of life measures. Some trials also look at the drug's pharmacokinetics (how the body processes the drug) and its long-term effectiveness and safety.
  • Are there any specific side effects being monitored in fedratinib trials? Yes, researchers are closely monitoring for various side effects, with particular attention to gastrointestinal events (such as nausea, diarrhea, and vomiting), changes in blood cell counts, and the potential development of Wernicke's encephalopathy (a neurological condition). Trials also assess changes in liver and kidney function, as well as other laboratory parameters.

Ongoing Clinical Trials on Fedratinib

  • Study on the Safety of Roginolisib and Ruxolitinib for Patients with Myelofibrosis Unresponsive to JAK Inhibitors

    Recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Italy Spain

  • Study on the Safety and Effectiveness of Fedratinib and Azacitidine for Patients with Accelerated Phase Myelofibrosis

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

  • Study Comparing Fedratinib with Drug Combination for Myelofibrosis in Patients Previously Treated with Ruxolitinib

    Not recruiting

    1 1 1 1
    Investigated diseases:
    Investigated drugs:
    Austria Belgium Czechia France Germany Hungary +4

  • Study of BMS-986158 Alone and with Ruxolitinib or Fedratinib for Patients with Intermediate or High Risk Myelofibrosis

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    France Germany Greece Italy Poland Romania +1

  • Study of Fedratinib and Nivolumab for Patients with Myelofibrosis Resistant to JAK-inhibitor Treatment

    Not recruiting

    1 1 1
    Investigated diseases:
    Investigated drugs:
    Germany

Glossary

  • Myelofibrosis: A rare blood cancer that affects the bone marrow, leading to scarring and impaired blood cell production.
  • JAK2: A protein involved in signaling within cells that plays a role in the development of myelofibrosis. Fedratinib works by inhibiting this protein.
  • Spleen volume reduction: A decrease in the size of the spleen, which is often enlarged in patients with myelofibrosis. This is a common measure of treatment effectiveness in clinical trials.
  • DIPSS: Dynamic International Prognostic Scoring System, a tool used to assess the risk level and prognosis of patients with myelofibrosis.
  • Pharmacokinetics: The study of how a drug moves through the body, including how it's absorbed, distributed, metabolized, and excreted.
  • AUC: Area Under the Curve, a measure used in pharmacokinetics to represent the total exposure to a drug over time.
  • Cmax: The maximum concentration of a drug in the blood after it has been administered.
  • Wernicke's encephalopathy: A neurological condition caused by thiamine (vitamin B1) deficiency, which can potentially occur as a rare side effect of fedratinib treatment.
  • MPN-SAF TSS: Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score, a tool used to measure the severity of symptoms in patients with myeloproliferative disorders.
  • CYP2C19 and CYP3A4: Enzymes in the liver that are involved in breaking down many medications, including fedratinib.

References

  1. https://clinicaltrials.gov/study/NCT05177211
  2. https://clinicaltrials.gov/study/NCT03755518
  3. https://clinicaltrials.eu/trial/study-comparing-fedratinib-with-drug-combination-for-myelofibrosis-in-patients-previously-treated-with-ruxolitinib/
  4. https://clinicaltrials.gov/study/NCT04446650
  5. https://clinicaltrials.gov/study/NCT03983161
  6. https://clinicaltrials.gov/study/NCT05883904