CLINICAL TRIALS PROFILE FOR PIPOBROMAN

All Clinical Trials for pipobroman

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT02577926 ↗	The Ruxo-BEAT Trial in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia	Active, not recruiting	Novartis	Phase 2	2015-10-01	The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprise a group of clonal hematological malignancies that are characterized by chronic myeloproliferation, splenomegaly, different degrees of bone marrow fibrosis, and disease-related symptoms including pruritus, night sweats, fever, weight loss, cachexia, and diarrhea. In addition, due to elevated numbers of leucocytes, erythrocytes and/or platelets, the disease course can be complicated by thromboembolic disease, hemorrhage, and leukemic transformation as well as myelofibrosis. Patients with polycythemia vera (PV) typically harbor an increased number of blood cells from all three hematopoietic cell lineages due to clonal amplification of hematopoetic stem cells, while patients with essential thrombocythemia (ET) typically show a predominant expansion of the megakaryocytic lineage. Most patients with PV below the age of 60 years are currently being treated with acetylsalicylic acid +/- phlebotomy only, and patients with low-risk ET have an almost normal life expectancy and often do not require specific treatment. However, PV- as well as ET-patients with a higher risk for complications require cytoreductive treatment. In addition, constitutional symptoms can be unbearable to patients even in the absence of bona fide high risk factors, and these patients may similarly benefit from antineoplastic therapy.
NCT02577926 ↗	The Ruxo-BEAT Trial in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia	Active, not recruiting	Novartis Pharmaceuticals	Phase 2	2015-10-01	The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprise a group of clonal hematological malignancies that are characterized by chronic myeloproliferation, splenomegaly, different degrees of bone marrow fibrosis, and disease-related symptoms including pruritus, night sweats, fever, weight loss, cachexia, and diarrhea. In addition, due to elevated numbers of leucocytes, erythrocytes and/or platelets, the disease course can be complicated by thromboembolic disease, hemorrhage, and leukemic transformation as well as myelofibrosis. Patients with polycythemia vera (PV) typically harbor an increased number of blood cells from all three hematopoietic cell lineages due to clonal amplification of hematopoetic stem cells, while patients with essential thrombocythemia (ET) typically show a predominant expansion of the megakaryocytic lineage. Most patients with PV below the age of 60 years are currently being treated with acetylsalicylic acid +/- phlebotomy only, and patients with low-risk ET have an almost normal life expectancy and often do not require specific treatment. However, PV- as well as ET-patients with a higher risk for complications require cytoreductive treatment. In addition, constitutional symptoms can be unbearable to patients even in the absence of bona fide high risk factors, and these patients may similarly benefit from antineoplastic therapy.
NCT02577926 ↗	The Ruxo-BEAT Trial in Patients With High-risk Polycythemia Vera or High-risk Essential Thrombocythemia	Active, not recruiting	RWTH Aachen University	Phase 2	2015-10-01	The Philadelphia chromosome negative myeloproliferative neoplasms (MPN) comprise a group of clonal hematological malignancies that are characterized by chronic myeloproliferation, splenomegaly, different degrees of bone marrow fibrosis, and disease-related symptoms including pruritus, night sweats, fever, weight loss, cachexia, and diarrhea. In addition, due to elevated numbers of leucocytes, erythrocytes and/or platelets, the disease course can be complicated by thromboembolic disease, hemorrhage, and leukemic transformation as well as myelofibrosis. Patients with polycythemia vera (PV) typically harbor an increased number of blood cells from all three hematopoietic cell lineages due to clonal amplification of hematopoetic stem cells, while patients with essential thrombocythemia (ET) typically show a predominant expansion of the megakaryocytic lineage. Most patients with PV below the age of 60 years are currently being treated with acetylsalicylic acid +/- phlebotomy only, and patients with low-risk ET have an almost normal life expectancy and often do not require specific treatment. However, PV- as well as ET-patients with a higher risk for complications require cytoreductive treatment. In addition, constitutional symptoms can be unbearable to patients even in the absence of bona fide high risk factors, and these patients may similarly benefit from antineoplastic therapy.
NCT01243944 ↗	Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)	Completed	Novartis Pharmaceuticals	Phase 3	2010-10-27	This pivotal phase III trial (CINC424B2301) is designed to compare the efficacy and safety of ruxolitinib (INC424) to Best Available Therapy (BAT) in participants with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).
NCT01243944 ↗	Study of Efficacy and Safety in Polycythemia Vera Subjects Who Are Resistant to or Intolerant of Hydroxyurea: JAK Inhibitor INC424 (INCB018424) Tablets Versus Best Available Care: (The RESPONSE Trial)	Completed	Incyte Corporation	Phase 3	2010-10-27	This pivotal phase III trial (CINC424B2301) is designed to compare the efficacy and safety of ruxolitinib (INC424) to Best Available Therapy (BAT) in participants with polycythemia vera (PV) who are resistant to or intolerant of hydroxyurea (HU).
NCT00241241 ↗	Efficacy and Safety of Pegylated Interferon Alfa in Polycythemia Vera	Completed	PV-Nord	Phase 2	2004-09-01	Interferon alfa is an effective treatment of polycythemia vera (PV), but about 20% of patients discontinue their treatment because of side effects and treatment schedule (three times per week administration). The pegylated form of interferon alfa-2a has shown a better tolerance in hepatitis patients and is administered only once a week. The purpose of this study is to determine efficacy and safety of pegylated interferon alfa-2a in the treatment of PV patients.

Clinical Trial Conditions for pipobroman

Condition Name

Condition Name for pipobroman
Intervention	Trials
Polycythemia Vera	2
Essential Thrombocythemia (ET)	1
Polycythemia Vera (PV)	1

Condition MeSH

Condition MeSH for pipobroman
Intervention	Trials
Polycythemia Vera	3
Polycythemia	3
Thrombocytosis	1
Thrombocythemia, Essential	1

Clinical Trial Locations for pipobroman

Trials by Country

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Trials by Country for pipobroman
Location	Trials
United States	18
Germany	11
France	2
Japan	1
Russian Federation	1

Trials by US State

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−

Trials by US State for pipobroman
Location	Trials
Washington	1
Texas	1
Tennessee	1
South Carolina	1
New Jersey	1

Clinical Trial Progress for pipobroman

Clinical Trial Phase

Clinical Trial Phase for pipobroman
Clinical Trial Phase	Trials
Phase 3	1
Phase 2	2

Clinical Trial Status

Clinical Trial Status for pipobroman
Clinical Trial Phase	Trials
Completed	2
Active, not recruiting	1

Clinical Trial Sponsors for pipobroman

Sponsor Name

Sponsor Name for pipobroman
Sponsor	Trials
Novartis Pharmaceuticals	2
Incyte Corporation	1
Novartis	1

Sponsor Type

Sponsor Type for pipobroman
Sponsor	Trials
Industry	4
Other	2

Pipobroman: Clinical Trials, Market Analysis, and Projections

Introduction

Pipobroman is an antineoplastic agent used in the treatment of myeloproliferative neoplasms, particularly polycythemia vera (PV) and essential thrombocythemia. Here, we will delve into the clinical trials, market analysis, and future projections for pipobroman.

Clinical Trials

Historical Context and Key Findings

One of the most significant clinical trials involving pipobroman is the study conducted by the French Polycythemia Study Group (FPSG), which compared pipobroman with hydroxyurea (HU) as first-line therapy in patients with PV. This randomized trial included 285 patients younger than 65 years and had a median follow-up of 16.3 years[1][4].

• Survival and Outcomes: The study revealed that patients treated with pipobroman had a shorter median overall survival compared to those treated with HU. The median overall survival was 15.4 years for the pipobroman arm versus 20.3 years for the HU arm[1][4].
• Leukemogenic Risk: A critical finding was that pipobroman is leukemogenic, meaning it increases the risk of developing acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). This makes pipobroman unsuitable for first-line therapy in PV patients[1][4].
• Switching Therapies: The study also analyzed the impact of switching therapies. Patients who switched from HU to pipobroman had a significantly increased risk of death compared to those who remained on HU[1].

Implications for Clinical Use

Given the leukemogenic risk associated with pipobroman, it is no longer recommended as a first-line treatment for PV. Instead, hydroxyurea and other safer alternatives are preferred. The long-term follow-up data from the FPSG study have been instrumental in guiding clinical practice and treatment algorithms for PV.

Market Analysis

Current Market Status

The market for polycythemia vera treatments is dominated by other therapies, with hydroxyurea being the mainstay for first-line treatment. Pipobroman, due to its leukemogenic risks, has seen a significant decline in its use and market share.

• Market Size: The overall market size for PV treatments was estimated to be USD 951.68 million in 2017, with hydroxyurea and other therapies like Jakafi (ruxolitinib) being the major contributors[2].
• Competitive Landscape: The market is highly competitive, with emerging therapies such as Besremi (an interferon-alpha 2b stimulant), Givinostat (a histone deacetylase inhibitor), and PTG-300 (a hepcidin mimetic) poised to enter the market. These new treatments are expected to further reduce the market share of pipobroman[2].

Market Drivers and Barriers

• Market Drivers: The increasing prevalence of PV, advancements in diagnostic techniques, and the introduction of new therapies are driving the market growth. However, pipobroman's use is hindered by its adverse safety profile[2].
• Market Barriers: The primary barrier for pipobroman is its leukemogenic risk, which has led to a decline in its prescription and use. Regulatory scrutiny and the availability of safer alternatives further limit its market potential[2].

Projections and Future Outlook

Declining Use

Given the adverse findings from clinical trials and the availability of safer and more effective treatments, the use of pipobroman is expected to continue declining.

• Replacement by New Therapies: Emerging therapies like Besremi, Givinostat, and PTG-300 are likely to capture a significant share of the market, further reducing the role of pipobroman in the treatment of PV[2].

Regulatory and Clinical Implications

• Regulatory Status: Pipobroman's regulatory status is likely to be reevaluated in light of the long-term safety data. It may face stricter regulations or even be withdrawn from the market in some jurisdictions.
• Clinical Guidelines: Clinical guidelines will continue to reflect the adverse safety profile of pipobroman, recommending its use only in very specific and limited circumstances, if at all[1][4].

Key Takeaways

• Clinical Trials: Pipobroman has been shown to be leukemogenic and is no longer recommended as a first-line treatment for PV based on long-term follow-up data.
• Market Analysis: The market for PV treatments is dominated by safer alternatives like hydroxyurea and emerging therapies, significantly reducing pipobroman's market share.
• Future Outlook: The use of pipobroman is expected to decline further due to its adverse safety profile and the introduction of new, safer therapies.

FAQs

What are the main findings from the FPSG study on pipobroman?

The FPSG study found that pipobroman is leukemogenic, increases the risk of AML/MDS, and has a shorter median overall survival compared to hydroxyurea. It is no longer recommended as a first-line treatment for PV[1][4].

Why is pipobroman not recommended for first-line treatment in PV?

Pipobroman is not recommended due to its leukemogenic risk and the availability of safer and more effective alternatives like hydroxyurea[1][4].

What are the emerging therapies that could replace pipobroman in the market?

Emerging therapies include Besremi, Givinostat, and PTG-300, which are expected to capture a significant market share due to their better safety and efficacy profiles[2].

How does the market size of PV treatments impact pipobroman?

The market size for PV treatments is growing, but pipobroman's share is declining due to its adverse safety profile and the introduction of new therapies[2].

What regulatory actions might be taken against pipobroman?

Pipobroman may face stricter regulations or even be withdrawn from the market in some jurisdictions due to its leukemogenic risk and the availability of safer alternatives[1][4].

How does the clinical use of pipobroman compare to other treatments like hydroxyurea?

Pipobroman has a poorer safety profile compared to hydroxyurea, which is the preferred first-line treatment for PV. Hydroxyurea has a longer median overall survival and lower risk of AML/MDS[1][4].

Sources

1. French Polycythemia Study Group. "Treatment of Polycythemia Vera With Hydroxyurea and Pipobroman." Journal of Clinical Oncology, vol. 29, no. 32, 2011, pp. 4241-4248.
2. ResearchAndMarkets.com. "Polycythemia Vera Market Insights, Epidemiology and Market Forecast-2030." Business Wire, 13 July 2020.
3. Health Canada. "Clinical trials and drug safety." Canada.ca, 22 May 2020.
4. French Polycythemia Study Group. "Treatment of polycythemia vera with hydroxyurea and pipobroman." PubMed, 10 October 2011.
5. DrugBank. "Pipobroman: Uses, Interactions, Mechanism of Action." DrugBank, 13 June 2005.