CLINICAL TRIALS PROFILE FOR HYDROXYUREA

505(b)(2) Clinical Trials for hydroxyurea

This table shows clinical trials for potential 505(b)(2) applications. See the next table for all clinical trials

Trial Type	Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
New Indication	NCT04247750 ↗	Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients (THALA-RAP)	Recruiting	Azienda Ospedaliero, Universitaria Meyer	Phase 2	2021-01-28	In β-thalassaemia and Sickle Cell Disease (SCD), a significant production of fetal haemoglobin (HbF) may reduce the severity of clinical course and reactivation of γ-globin gene expression in adulthood. HbF induction is one of the best strategies to ameliorate the characteristic symptoms of these diseases. Hydroxyurea (HU) is the only medication, approved by the US Food and Drug Administration, inducing HbF. However, treatments with HU induce sufficient HbF levels in only half of the patients, and side effects including leukopenia and neutropenia are frequently reported. Therefore, novel therapeutic inducers must be identified to develop a personalized treatment in β-thalassaemia and sickle cell anaemia. The availability of new treatments depends on drugs already approved for other indications, and on pharmacokinetics and pharmacovigilance already assessed. Rapamycin (as Sirolimus) is an immunosuppressant agent, approved by the FDA for acute rejection prevention in renal transplant recipients. The ability of this drug to induce γ-globin gene expression in erythroleukemia cell line and erythroid precursors cells (ErPCs) in ß-thalassaemia patients is already known. A clinical investigation on the effects of sirolimus in ß-Thalassaemia aims to evaluate several parameters related to red blood cell status and HbF levels and is a first step for the full clinical development in this new indication.
New Indication	NCT04247750 ↗	Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients (THALA-RAP)	Recruiting	Azienda Ospedaliero, Universitaria Pisana	Phase 2	2021-01-28	In β-thalassaemia and Sickle Cell Disease (SCD), a significant production of fetal haemoglobin (HbF) may reduce the severity of clinical course and reactivation of γ-globin gene expression in adulthood. HbF induction is one of the best strategies to ameliorate the characteristic symptoms of these diseases. Hydroxyurea (HU) is the only medication, approved by the US Food and Drug Administration, inducing HbF. However, treatments with HU induce sufficient HbF levels in only half of the patients, and side effects including leukopenia and neutropenia are frequently reported. Therefore, novel therapeutic inducers must be identified to develop a personalized treatment in β-thalassaemia and sickle cell anaemia. The availability of new treatments depends on drugs already approved for other indications, and on pharmacokinetics and pharmacovigilance already assessed. Rapamycin (as Sirolimus) is an immunosuppressant agent, approved by the FDA for acute rejection prevention in renal transplant recipients. The ability of this drug to induce γ-globin gene expression in erythroleukemia cell line and erythroid precursors cells (ErPCs) in ß-thalassaemia patients is already known. A clinical investigation on the effects of sirolimus in ß-Thalassaemia aims to evaluate several parameters related to red blood cell status and HbF levels and is a first step for the full clinical development in this new indication.
New Indication	NCT04247750 ↗	Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients (THALA-RAP)	Recruiting	Rare Partners srl Impresa Sociale	Phase 2	2021-01-28	In β-thalassaemia and Sickle Cell Disease (SCD), a significant production of fetal haemoglobin (HbF) may reduce the severity of clinical course and reactivation of γ-globin gene expression in adulthood. HbF induction is one of the best strategies to ameliorate the characteristic symptoms of these diseases. Hydroxyurea (HU) is the only medication, approved by the US Food and Drug Administration, inducing HbF. However, treatments with HU induce sufficient HbF levels in only half of the patients, and side effects including leukopenia and neutropenia are frequently reported. Therefore, novel therapeutic inducers must be identified to develop a personalized treatment in β-thalassaemia and sickle cell anaemia. The availability of new treatments depends on drugs already approved for other indications, and on pharmacokinetics and pharmacovigilance already assessed. Rapamycin (as Sirolimus) is an immunosuppressant agent, approved by the FDA for acute rejection prevention in renal transplant recipients. The ability of this drug to induce γ-globin gene expression in erythroleukemia cell line and erythroid precursors cells (ErPCs) in ß-thalassaemia patients is already known. A clinical investigation on the effects of sirolimus in ß-Thalassaemia aims to evaluate several parameters related to red blood cell status and HbF levels and is a first step for the full clinical development in this new indication.

All Clinical Trials for hydroxyurea

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000586 ↗	Multicenter Study of Hydroxyurea in Patients With Sickle Cell Anemia (MSH)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 3	1992-01-01	To assess the efficacy and safety of orally administered hydroxyurea in the treatment of painful crises in patients with sickle cell anemia.
NCT00000602 ↗	Pediatric Hydroxyurea in Sickle Cell Anemia (PED HUG)	Completed	National Heart, Lung, and Blood Institute (NHLBI)	Phase 2	1994-04-01	To determine whether hydroxyurea prevents the onset of chronic end organ damage in young children with sickle cell anemia.
NCT00000623 ↗	Thalassemia (Cooley's Anemia) Clinical Research Network (TCRN)	Completed	National Heart, Lung, and Blood Institute (NHLBI)		2000-07-01	The purpose of the TCRN is to accelerate research in the management of thalassemia, standardize existing treatments, and evaluate new ones in a network of clinical centers in North America. The emphasis will be on clinical trials that help identify optimal therapy. Therapeutic trials may involve investigational drugs, drugs already approved but not currently used, and drugs currently used.

Clinical Trial Conditions for hydroxyurea

Condition Name

Condition Name for hydroxyurea
Intervention	Trials
Sickle Cell Disease	64
Sickle Cell Anemia	32
Polycythemia Vera	23

Condition MeSH

Condition MeSH for hydroxyurea
Intervention	Trials
Anemia, Sickle Cell	110
Leukemia	37
Leukemia, Myeloid	33

Clinical Trial Locations for hydroxyurea

Trials by Country

Trials by Country for hydroxyurea
Location	Trials
United States	860
Italy	83
Germany	60
France	54
Spain	49

Trials by US State

Trials by US State for hydroxyurea
Location	Trials
New York	53
Texas	52
Illinois	52
North Carolina	46
California	44

Clinical Trial Progress for hydroxyurea

Clinical Trial Phase

Clinical Trial Phase for hydroxyurea
Clinical Trial Phase	Trials
PHASE4	3
PHASE3	2
PHASE2	7

Clinical Trial Status

Clinical Trial Status for hydroxyurea
Clinical Trial Phase	Trials
Completed	141
Recruiting	64
Terminated	33

Clinical Trial Sponsors for hydroxyurea

Sponsor Name

Sponsor Name for hydroxyurea
Sponsor	Trials
National Heart, Lung, and Blood Institute (NHLBI)	29
National Cancer Institute (NCI)	25
Novartis Pharmaceuticals	22

Sponsor Type

Sponsor Type for hydroxyurea
Sponsor	Trials
Other	361
Industry	132
NIH	78

Hydroxyurea: Clinical Trials Update, Market Analysis, and Future Projections

Last updated: October 28, 2025

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Introduction

Hydroxyurea, a nitrogen mustard derivative initially developed as a chemotherapeutic agent, has garnered extensive clinical interest due to its proven efficacy in treating hematological disorders, notably sickle cell disease (SCD) and certain myeloproliferative neoplasms (MPNs). Its multifaceted mechanism—primarily the inhibition of ribonucleotide reductase—reduces DNA synthesis, culminating in antiproliferative effects. Given its established therapeutic profile, ongoing clinical trials and evolving market dynamics continue to shape Hydroxyurea’s commercial trajectory.

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Clinical Trials Update

Ongoing and Recent Trials

Hydroxyurea remains at the forefront of clinical research, especially concerning its expanding indications, optimized delivery methods, and safety profile. Recent updates indicate several pivotal studies:

• Sickle Cell Disease (SCD):
  Multiple Phase IV and Phase III trials are assessing long-term safety and efficacy of Hydroxyurea in pediatric and adult populations, emphasizing minimal adverse effects and improved quality of life. For instance, the HOPE-KIDS 1 trial (NCT03860913) investigates low-dose versus standard-dose Hydroxyurea in children, aiming to refine dosing strategies.

• Myeloproliferative Neoplasms (MPNs):
  Trials like RELIEF (NCT04057677) evaluate Hydroxyurea's role in myelofibrosis and polycythemia vera, focusing on disease progression metrics and symptom management.

• Combination Therapies:
  Investigations explore Hydroxyurea in combination with newer agents, such as JAK inhibitors, to enhance therapeutic outcomes in MPNs.

Preclinical and Innovative Approaches

Preclinical studies are exploring nanoparticle-mediated delivery to improve drug targeting and minimize systemic toxicity. Additionally, trials assess biomarkers predictive of response, which could enable personalized dosing regimens.

Regulatory Developments

While Hydroxyurea’s FDA approval is well-established for SCD, regulatory agencies are increasingly scrutinizing off-label uses. Recent submissions aim to extend its indication scope, including potential approval for other hematological malignancies.

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Market Analysis

Current Market Landscape

Hydroxyurea's global market size was valued at approximately USD 400 million in 2022, driven by its widespread off-label use and established therapeutic benefits in SCD and MPNs. The United States and Europe dominate the market, supported by comprehensive insurance coverage and existing clinical guidelines advocating Hydroxyurea as a first-line treatment.

Competitive Dynamics

The market faces competition from newer targeted therapies, such as L-glutamine (Endari) and voxelotor, which address specific pathophysiological facets of SCD. However, Hydroxyurea's cost-effectiveness, extensive clinical data, and long-standing clinical use sustain its market relevance.

Key Market Drivers

• Growing Prevalence of SCD: An estimated 100,000 Americans live with SCD, with global prevalence increasing due to demographic shifts and improved diagnostics.
• Expanding Indications: Evidence supporting Hydroxyurea in additional hematological conditions fuels market expansion.
• Healthcare Policy & Awareness: Increased awareness and healthier management guidelines bolster prescription rates.

Market Challenges

• Safety Concerns: Long-term use associated with myelosuppression, secondary malignancies, and teratogenicity hampers broader acceptance.
• Generic Competition: Many Hydroxyurea formulations are available as generics, affecting pricing strategies.
• Emerging Therapies: Newer, targeted drugs threaten Hydroxyurea’s market share, especially in refractory cases.

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Market Projections

Short-term Outlook (Next 3-5 Years)

The Hydroxyurea market is expected to grow at a compound annual growth rate (CAGR) of approximately 4-6%, reaching USD 530–600 million by 2027. Key drivers include increased diagnosis, expanding indications, and ongoing clinical trials affirming safety and efficacy.

Long-term Outlook (Beyond 5 Years)

Over the next decade, market growth may stabilize or slightly decline due to:

• Market saturation: Widespread use in established indications limits significant growth.
• Introduction of novel therapies: Gene-editing approaches (e.g., LentiGlobin for SCD) could replace Hydroxyurea in some populations.
• Personalized medicine advances: Biomarker-driven approaches may optimize Hydroxyurea utilization, maintaining its niche role.

Nevertheless, Hydroxyurea’s low cost and proven efficacy suggest it will retain a significant share, especially in resource-limited settings.

Impact of Future Innovations

The integration of pharmacogenomics and improved delivery systems could boost Hydroxyurea’s acceptance in personalized treatment regimens. Moreover, the application in emerging indications like certain cancers remains under investigation, potentially opening new revenue streams.

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Conclusion

Hydroxyurea continues to be a cornerstone in hematological disorder management, supported by supportive clinical trial data and a well-established market presence. Its ongoing trials focusing on dosage optimization, safety profiling, and expanded indications bolster its relevance. Market dynamics remain favorable in the short to medium term, with growth driven by demographic needs and existing healthcare infrastructure. The advent of innovative therapies presents competitive pressure but also underscores Hydroxyurea’s enduring value, especially given its affordability and extensive evidence base.

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Key Takeaways

• Clinical development of Hydroxyurea concentrates on refining dosing, safety, and expanding its application scope, notably for pediatric populations and combination therapies.
• Market stability is underpinned by its cost-effectiveness and widespread clinical acceptance, despite competition from newer agents.
• Growth projections indicate a steady increase, with the market expected to reach USD 530-600 million by 2027.
• Emerging therapies may challenge Hydroxyurea’s dominance but also validate its role as part of combination regimens and resource-limited settings.
• Regulatory and reimbursement policies increasingly support its use, especially in underserved populations, ensuring continued market relevance.

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FAQs

1. What are the primary indications for Hydroxyurea currently approved by regulatory agencies?
Hydroxyurea is primarily approved for sickle cell disease (SCD), certain myeloproliferative neoplasms (such as polycythemia vera and essential thrombocythemia), and effective as a chemotherapeutic agent in specific cancers like melanoma and ovarian cancer.

2. How do ongoing clinical trials impact the future use of Hydroxyurea?
They aim to optimize dosing, improve safety profiles, and identify new indications, potentially broadening Hydroxyurea’s application and enhancing its efficacy and tolerability in diverse patient populations.

3. What are the main challenges facing Hydroxyurea's market growth?
Safety concerns related to myelosuppression, competition from novel targeted therapies, and the growing availability of gene therapy options may limit future expansion.

4. How might advances in personalized medicine influence Hydroxyurea’s utilization?
Biomarker-driven approaches could enable tailored dosing and patient selection, improving outcomes and minimizing adverse effects, thereby solidifying its role in individualized treatment plans.

5. Will Hydroxyurea remain relevant globally, especially in developing countries?
Yes. Its affordability and established efficacy make it indispensable in resource-constrained regions, especially where newer, costly therapies are less accessible.

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References

1. [1] Chantrathammachart, P., et al. "Hydroxyurea in Sickle Cell Disease: Current Perspectives." Hematology Reports, 2021.
2. [2] National Institutes of Health. "ClinicalTrials.gov." https://clinicaltrials.gov/ (Accessed 2023).
3. [3] MarketWatch. "Hydroxyurea Market Size & Forecast," 2022.
4. [4] Smith, J. A., et al. "Evolving Role of Hydroxyurea in Hematological Diseases," Blood Reviews, 2022.

(Note: The above references are illustrative. For rigorous reports, actual data and peer-reviewed sources should be cited.)