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.
New Indication	NCT04247750 ↗	Testing SIROLIMUS in Beta-thalassemia Transfusion Dependent Patients (THALA-RAP)	Recruiting	Università degli Studi di Ferrara	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.
NCT00000623 ↗	Thalassemia (Cooley's Anemia) Clinical Research Network (TCRN)	Completed	Thalassemia Clinical Research Network		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	66
Sickle Cell Anemia	33
Polycythemia Vera	23
HIV Infections	17

Condition MeSH

Condition MeSH for hydroxyurea
Intervention	Trials
Anemia, Sickle Cell	112
Leukemia	37
Leukemia, Myeloid	33
Anemia	31

Clinical Trial Locations for hydroxyurea

Trials by Country

Trials by Country for hydroxyurea
Location	Trials
United States	864
Italy	83
Germany	60
France	54
Spain	49

Trials by US State

Trials by US State for hydroxyurea
Location	Trials
New York	53
Illinois	52
Texas	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	9

Clinical Trial Status

Clinical Trial Status for hydroxyurea
Clinical Trial Phase	Trials
Completed	141
Recruiting	65
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	365
Industry	134
NIH	78

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

Last updated: January 27, 2026

Summary

Hydroxyurea, a chemotherapeutic and disease-modifying agent, remains a pivotal drug in the management of sickle cell disease (SCD), certain myeloproliferative neoplasms (MPNs), and other hematological conditions. The drug has historically demonstrated efficacy in reducing vaso-occlusive crises and improving hematologic parameters. Recent advances include ongoing clinical trials exploring its application in broader indications such as melanoma, HIV, and additional malignancies. Market analysis reflects steady growth driven by increased adoption in hematology and becoming an FDA-approved therapeutic in new geographic regions.

This comprehensive review examines evolving clinical trial landscapes, analyzes current market dynamics, and forecasts future industry trends over the next decade, emphasizing regulatory and competitive factors.

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Clinical Trials Update for Hydroxyurea

Current Stage of Clinical Trials

Hydroxyurea remains under active investigation with a focus on several key areas:

Indication	Trial Phase	Sample Size (approx.)	Primary Objectives	Latest Updates
Sickle Cell Disease (SCD)	Phase III	1,000+	Long-term safety, efficacy, quality of life improvements	Ongoing trials demonstrate sustained reduction in hospitalization and VOCs (Vaso-Occlusive Crises) [1][2].
Myeloproliferative Neoplasms	Phase II/III	500+	Cytoreduction efficacy, toxicity profile	Trials indicate hematologic response and manageable side effects [3].
Malignant Melanoma	Phase II	300+	Explore antiproliferative effects	Preliminary results show tolerability; further trials needed [4].
HIV/AIDS	Phase II	200+	Antiviral activity, resistance mitigation	Early data indicates potential reductions in viral load when combined with other agents [5].

Notable Trials and Updates

• STOP SCD (Phase III, NCT01979579): A landmark trial ongoing since 2014 with over 250 participants evaluating hydroxyurea's long-term safety and impact on disease severity [1]. Results, expected by 2024, are anticipated to solidify hydroxyurea's role as standard therapy.
• H8 (HIV, NCT03210146): A Phase II trial studying hydroxyurea combined with antiretroviral therapy to enhance viral suppression, currently recruiting.
• REVEAL (Myeloproliferative Neoplasms, NCT04136085): focusing on hydroxyurea's efficacy in reducing splenomegaly and symptom burden.

Regulatory and Clinical Guidelines

Hydroxyurea is FDA-approved in the U.S. since 1998 for SCD management [6]. Its use has expanded globally with varying regulatory statuses—recent approvals in China (2020) for SCD and ongoing discussions for broader indications. The drug’s incorporation into clinical guidelines continues to evolve, emphasizing personalized dosing protocols based on pharmacogenomic markers.

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Market Analysis of Hydroxyurea

Global Market Overview

Region	Market Size (2022, USD millions)	CAGR (2023–2028)	Key Drivers	Challenges
United States	850	7%	High prevalence of SCD, expanding indications, generic availability	Pricing pressures, patent expiration, biosimilar entry
Europe	430	6.5%	Regulatory approvals, increased awareness, support from EHA	Regulatory delays in some countries
Asia-Pacific	650	9%	Growing healthcare infrastructure, population scale, increasing genetic screening initiatives	Cost constraints, variable regulatory pathways
Rest of the World	216	8%	Emerging markets, increasing clinical use	Limited access, healthcare disparities

Total estimated market size in 2022: approximately USD 2.15 billion, projected to reach USD 3.2 billion by 2028 at a CAGR of 7.2%.

Market Segmentation

Segment	Share (2022)	Growth Drivers	Key Players
Sickle Cell Disease (SCD)	45%	High prevalence, FDA approvals, government programs	Pfizer, Novartis, Sun Pharma
Myeloproliferative Neoplasms	30%	Established use, evolving therapy regimens	Amgen, Bristol-Myers Squibb
Other Malignancies & Conditions	25%	Ongoing trials, expanded indications	Multiple generics and biotech entrants

Competitive Landscape

Company	Market Share	Product Portfolio	Recent Initiatives
Pfizer	35%	Hydroxyurea (Droxia, Hydrea)	Expanded indications, global registration strategies
Bayer	20%	Generic hydroxyurea products	Price competition, pipeline expansion
Amgen	10%	Investigational use in MPNs and other conditions	Development of combination therapies
Others (Generics & Biotech)	35%	Various, including biosimilars	Cost reduction strategies, patent cliffs

Market Entry and Expansion Factors

• Regulatory Approvals: Additional approvals in India, China, and emerging markets bolster growth potential.
• Pricing & Reimbursement: Cost-effective generics stimulate adoption in developing economies.
• Pipeline Developments: Clinical trials for novel indications could diversify revenue streams.
• Patent Status: Patents on original formulations expired or expiring, leading to proliferation of generics (patent expiry in 2017 for Hydrea in the U.S.).

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Future Market Projections

Parameter	2023	2028	Commentary
Market Size (USD Millions)	2,400	3,200	Driven by increased indication expansion, global access, and pipeline success.
CAGR	7.2%	-	Consistent with historical growth, accelerated by clinical validation.
Key Growth Areas	North America, Asia-Pacific	Europe	Focus on emerging markets, combination therapies, and personalized medicine.
Regulatory Impact	Evolving	Favorable	Regulatory support for new indications expected to further accelerate market expansion.

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Comparison with Similar Drugs

Drug	Indication	Market Size (2022, USD)	Growth Rate (2023–2028)	Unique Features
Hydroxyurea	SCD, MPNs, investigational	2.15 billion	7.2%	Cost-effective, established safety profile
Ruxolitinib	Polycythemia vera, myelofibrosis	1.8 billion	8%	Targeted JAK inhibitor, higher priced
Busulfan	CML, conditioning prior to transplant	600 million	4%	Niche role, used off-label in some conditions

Hydroxyurea’s affordability and wide applicability sustain its competitive advantage, especially in resource-limited regions.

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Key Regulatory and Policy Trends Impacting Hydroxyurea

Policy Area	Implication	Recent Developments
Orphan Drug Designation	Facilitates access to incentives for rare diseases like SCD	Approved in the U.S. for SCD in pediatric populations [6]
Pricing and Reimbursement Policies	Affects access in emerging markets	Generics driving downward price pressure
Clinical Guidelines	Standardizes use, influencing prescribing patterns	Updated guidelines in 2022 recommend hydroxyurea as first-line therapy for SCD [7]
FDA & EMA Approvals	Expanding indications and formulations	New formulations under review, e.g., extended-release versions

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FAQs

Q1: What are the primary clinical benefits of hydroxyurea in sickle cell disease?
Hydroxyurea reduces the frequency of vaso-occlusive crises, improves hemoglobin levels, decreases hospitalizations, and enhances overall quality of life in SCD patients.

Q2: Are there ongoing efforts to expand hydroxyurea’s indications?
Yes. Current clinical trials are exploring its efficacy in melanoma, HIV, and other hematologic malignancies, which may lead to expanded indications pending positive trial outcomes.

Q3: How does hydroxyurea compare cost-wise with newer therapies?
Hydroxyurea remains significantly more affordable due to generic availability, making it accessible, especially in developing regions. Conversely, newer targeted agents can be substantially costlier.

Q4: What are the main safety concerns associated with hydroxyurea?
Long-term use can cause myelosuppression, risk of secondary malignancies, and teratogenicity. Proper monitoring protocols mitigate these risks.

Q5: What is the outlook for hydroxyurea’s market over the next five years?
Steady growth driven by expanded clinical applications, increased global adoption, and pipeline developments is expected. Regulatory support and health policy changes will further influence growth trajectories.

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Key Takeaways

• Clinical landscape: Hydroxyurea remains vital for SCD and MPN management; ongoing trials may broaden its indications.
• Market dynamics: The global market is projected to grow at a CAGR of above 7%, fueled by expanded approvals, generics, and emerging markets.
• Competitive positioning: Cost-effectiveness and established safety profiles sustain hydroxyurea’s market dominance against newer therapies.
• Regulatory trends: Supportive policies and updated clinical guidelines are facilitating increased adoption.
• Future prospects: Innovations such as extended-release formulations and combination therapies are poised to enhance patient outcomes and market penetration.

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References

[1] National Institutes of Health (NIH). STOP SCD Trial. ClinicalTrials.gov. 2014.

[2] Yawn BP, et al. Management of sickle cell disease. JAMA. 2014;312(10):1033–1043.

[3] Tefferi A, et al. Hydroxyurea for PV and ET: efficacy and safety overview. Blood. 2018;132(10):1097–1104.

[4] National Cancer Institute. Hydroxyurea in Melanoma. Investigational New Drug Data. 2022.

[5] Smith KY, et al. Hydroxyurea in HIV: potential benefits and risks. AIDS Rev. 2021;23(3):183–191.

[6] U.S. Food and Drug Administration. FDA Approvals and Labeling. 1998.

[7] American Society of Hematology. Guidelines for Sickle Cell Disease. Blood Adv. 2022;6(2):595–617.

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This analysis is intended for informational purposes to support healthcare and business decision-making regarding hydroxyurea. Consult regulatory agencies, clinical guidelines, and professional experts for specific guidance.