CLINICAL TRIALS PROFILE FOR DARAPRIM

All Clinical Trials for DARAPRIM

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00065390 ↗	Pyrimethamine to Treat Autoimmune Lymphoproliferative Syndrome	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 1	2003-07-01	This study will examine whether the drug pyrimethamine can shrink lymph nodes and spleen in patients with autoimmune lymphoproliferative syndrome (ALPS). In this disease, lymphocytes (white blood cells) do not die as they normally would. As a result, patients have enlarged lymph glands, spleen, or liver, and other problems that may involve blood cell counts and autoimmune disease (overactivity of the immune system). Pyrimethamine is an orally administered antibiotic that has been used to treat or prevent malaria and toxoplasma, and may be effective in shrinking lymph nodes and spleen. Patients with ALPS who are between 2 and 70 years of age and have had lymph gland enlargement for at least 1 year may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood tests, and possibly a bone marrow test. Females of reproductive age will be screened with a urine pregnancy test. Women who are capable of becoming pregnant must use an effective method of birth control during the entire study period, because, taken during early months of pregnancy, pyrimethamine can cause birth defects in the fetus. Women who are pregnant or nursing are excluded from the study. Participants will undergo the following tests and procedures: - CT scan: For this test, the patient lies still in the CT scanner while images are taken of the neck, chest, and stomach area. A contrast dye is injected into a vein to brighten the CT images. Very young children will be evaluated on a case by case basis to determine whether a CT scan will be performed. - Bone marrow biopsy: Participants undergo this test to rule out underlying bone marrow disease if they have not had a bone marrow test done in the last six months prior to enrolling in pyrimethamine study, as pyrimethamine can affect bone marrow function. Under local anesthesia, a needle is inserted into the back part of the hipbone and a small amount of marrow is removed. (Children are sedated for this test.) - Leukapheresis: This is a procedure for collecting a small proportion of circulating white blood cells while conserving the majority of blood cells. Specifically, blood is drawn from a needle placed in an arm vein and is directed into a cell separator machine, which separates the blood cells by spinning. A small proportion of circulating white cells are removed, and the red cells, platelets, plasma and majority of white cells are returned to the patient's blood circulation. Only patients who are 7 years of age or older and weigh at least 55 pounds undergo this procedure. Other participants who choose not to have apheresis will have about 3 tablespoons of blood drawn instead. - Pyrimethamine administration: When the above tests are completed, participants begin taking pyrimethamine. The dose is determined according to the individual's weight and is gradually increased during the study period. Patients take the drug twice a week for a total of 12 weeks. - Blood tests: Blood samples are collected during weeks 2, 4, 6, 8, and 10 after beginning treatment, and 2 weeks after the last dose of pyrimethamine. The purpose of these blood tests is to check for possible drug-related side effects. Patients who develop a skin rash, mouth sores or other side effects may have one or more doses of the treatment drug withheld. When indicated, the patient will be directed to stop taking the study drug. If needed, drug side effects will be treated with a vitamin supplement, folinic acid, taken by mouth, 3 times weekly. - Evaluations at the NIH Clinical Center will comprise of a pretreatment visit, one end of treatment visit at the end of 12 weeks and an optional post-treatment visit 3months after stopping pyrimethamine therapy. Patients who respond well to treatment may be asked to return to NIH for additional visits at 3, 6, and 12 months after the treatment has ended for repeat evaluations. If their lymph glands or spleen become much larger after stopping pyrimethamine, they will be offered treatment for another 12 weeks. If they respond to the second course of treatment, they will return to NIH again after 3, 6, and 12 months. If the symptoms return again, patients will be asked to resume treatment for an additional 6 months or more. They will have blood drawn periodically by their private physician and will return to NIH for evaluation every 12 weeks.
NCT00300404 ↗	Effect of Specific Anti-Toxoplasmatic Add-on Medication in Toxoplasma Gondii Seropositive Individuals With Schizophrenia or Major Depression	Completed	Stanley Medical Research Institute	Phase 3	2002-01-01	We investigate whether the add-on specific antitoxoplasmatic medication has positive effects in individuals with schizophrenia or major depression seropositive for Toxoplasma gondii (TG) infection. As TG modulates neurotransmitter metabolism affecting serotonin and dopamine we hypothesize that this chronic persistent infection might play a role for depressive and psychotic symptomatology. Therefore, on the basis of an ex juvantibus approach, specific anti TG medication might further improve psychiatric symptomatology in affected patients. This is investigated in a double-blind, placebo-controlled, randomized treatment trial.
NCT00300404 ↗	Effect of Specific Anti-Toxoplasmatic Add-on Medication in Toxoplasma Gondii Seropositive Individuals With Schizophrenia or Major Depression	Completed	Zentrum für Integrative Psychiatrie	Phase 3	2002-01-01	We investigate whether the add-on specific antitoxoplasmatic medication has positive effects in individuals with schizophrenia or major depression seropositive for Toxoplasma gondii (TG) infection. As TG modulates neurotransmitter metabolism affecting serotonin and dopamine we hypothesize that this chronic persistent infection might play a role for depressive and psychotic symptomatology. Therefore, on the basis of an ex juvantibus approach, specific anti TG medication might further improve psychiatric symptomatology in affected patients. This is investigated in a double-blind, placebo-controlled, randomized treatment trial.
NCT01066663 ↗	Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Recruiting	Beth Israel Deaconess Medical Center	Phase 1/Phase 2	2010-03-01	In this research study we will start by looking for the highest dose of pyrimethamine that can be given safely to CLL patients without severe or unmanageable side effects. This dose will then be used for a larger Phase II study to assess the efficacy of pyrimethamine for the treatment of CLL/SLL. Pyrimethamine is an antibiotic that is used for the treatment of certain infections. Previous research studies have shown that pyrimethamine may target a protein in tumor cells, called STAT3, which may be important for the growth of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) cells. Pyrimethamine can kill CLL/SLL cells in the laboratory, and we are therefore undertaking this study to assess whether pyrimethamine will result in clinical benefit or tumor responses in CLL in patients.
NCT01066663 ↗	Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Recruiting	Brigham and Women's Hospital	Phase 1/Phase 2	2010-03-01	In this research study we will start by looking for the highest dose of pyrimethamine that can be given safely to CLL patients without severe or unmanageable side effects. This dose will then be used for a larger Phase II study to assess the efficacy of pyrimethamine for the treatment of CLL/SLL. Pyrimethamine is an antibiotic that is used for the treatment of certain infections. Previous research studies have shown that pyrimethamine may target a protein in tumor cells, called STAT3, which may be important for the growth of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) cells. Pyrimethamine can kill CLL/SLL cells in the laboratory, and we are therefore undertaking this study to assess whether pyrimethamine will result in clinical benefit or tumor responses in CLL in patients.
NCT01066663 ↗	Pyrimethamine for the Treatment of Relapsed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma	Recruiting	Lymphoma Research Foundation	Phase 1/Phase 2	2010-03-01	In this research study we will start by looking for the highest dose of pyrimethamine that can be given safely to CLL patients without severe or unmanageable side effects. This dose will then be used for a larger Phase II study to assess the efficacy of pyrimethamine for the treatment of CLL/SLL. Pyrimethamine is an antibiotic that is used for the treatment of certain infections. Previous research studies have shown that pyrimethamine may target a protein in tumor cells, called STAT3, which may be important for the growth of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) cells. Pyrimethamine can kill CLL/SLL cells in the laboratory, and we are therefore undertaking this study to assess whether pyrimethamine will result in clinical benefit or tumor responses in CLL in patients.

Clinical Trial Conditions for DARAPRIM

Condition Name

Condition Name for DARAPRIM
Intervention	Trials
HIV-1-infection	1
Lymphatic Disease	1
Lymphoproliferative Disorder	1
Major Depression	1

Condition MeSH

Condition MeSH for DARAPRIM
Intervention	Trials
Leukemia, Lymphocytic, Chronic, B-Cell	1
Preleukemia	1
Lymphatic Diseases	1
Leukemia	1

Clinical Trial Locations for DARAPRIM

Trials by Country

Trials by Country for DARAPRIM
Location	Trials
United States	6
Germany	1
Korea, Republic of	1
Sweden	1
Italy	1

Trials by US State

Trials by US State for DARAPRIM
Location	Trials
New York	2
Missouri	1
Texas	1
Massachusetts	1
Maryland	1

Clinical Trial Progress for DARAPRIM

Clinical Trial Phase

Clinical Trial Phase for DARAPRIM
Clinical Trial Phase	Trials
Phase 3	1
Phase 1/Phase 2	3
Phase 1	3

Clinical Trial Status

Clinical Trial Status for DARAPRIM
Clinical Trial Phase	Trials
Completed	5
Withdrawn	1
Not yet recruiting	1

Clinical Trial Sponsors for DARAPRIM

Sponsor Name

Sponsor Name for DARAPRIM
Sponsor	Trials
Montefiore Medical Center	2
Muscular Dystrophy Association	1
Weill Medical College of Cornell University	1

Sponsor Type

Sponsor Type for DARAPRIM
Sponsor	Trials
Other	15
NIH	1

Clinical Trials Update, Market Analysis, and Projection for Daraprim

Last updated: October 30, 2025

Introduction

Daraprim (pyrimethamine) remains a notable player within the pharmacopeia against parasitic infections, particularly toxoplasmosis and certain forms of malaria. Its historical significance was magnified in 2015 when Turing Pharmaceuticals acquired exclusive rights and drastically increased the drug’s price, turning it into a symbol of pharmaceutical pricing controversy. Despite this, Daraprim continues to hold clinical relevance, especially among niche patient populations. This report provides a comprehensive analysis of current clinical trials, market dynamics, and future projections for Daraprim.

Clinical Trials Overview

Current and Ongoing Trials

Recent years have seen limited clinical trials focused specifically on Daraprim; however, the drug remains integral to evolving treatment protocols, especially in combination therapies. As per ClinicalTrials.gov, notable studies include:

• Toxoplasmosis Treatment in Immunocompromised Patients: Several trials evaluate Daraprim’s efficacy with adjunct therapies in HIV-positive cohorts. Ongoing studies aim to optimize dosing regimens to reduce adverse effects while maintaining efficacy [1].

• Malaria in Non-Endemic Regions: Trials assess Daraprim’s role in prophylactic settings for travelers and immunocompromised individuals, especially where resistance to first-line treatments emerges [2].

• Combination Therapy Trials: Research evaluates Daraprim in combination with agents such as sulfadiazine or atovaquone, exploring synergistic effects to improve treatment outcomes in toxoplasmosis and malaria [3].

Recent Outcomes and Implications

Although no high-profile phase III trials are actively recruiting, existing studies suggest that Daraprim:

• Maintains high efficacy in toxoplasmosis, especially when integrated into combination therapies.
• Exhibits a manageable safety profile, with adverse effects like gastrointestinal disturbances and hematological issues manageable with monitoring.
• Shows promise for new indications, such as drug-resistant Plasmodium strains, though data remain preliminary.

Research Gaps and Future Directions

Despite its longstanding use, notable gaps include:

• Limited exploration into Daraprim’s potential for newer parasitic diseases.
• Insufficient data on long-term safety profiles in diverse populations.
• The necessity for large-scale randomized controlled trials (RCTs) to validate alternative dosing strategies.

Future clinical research is likely to focus on precision medicine approaches, dosing optimization in immunosuppressed individuals, and combination protocols to reduce resistance.

Market Dynamics

Current Market Landscape

Despite its age, Daraprim retains niche market significance:

• Market Segments: Primarily used in hospital settings for toxoplasmosis, particularly in immunocompromised patients such as those with HIV/AIDS or undergoing chemotherapy.
• Demand Drivers: The continued prevalence of toxoplasmosis in immunodeficient populations sustains its demand, alongside the limited availability of newer, more affordable alternatives.
• Pricing and Accessibility: Post-2015 controversy, the drug's pricing stabilized but remains costly, limiting accessibility in low-income regions. The drug’s patent exclusivity and manufacturing complexities contribute to pricing rigidity [4].

Competitive Landscape

There are alternative therapies for toxoplasmosis, including:

• Clindamycin: Often used in combination with pyrimethamine.
• Atovaquone: An alternative, especially in cases of pyrimethamine intolerance.
• Primaquine: Used in some malaria contexts.

However, Daraprim’s unique mechanism targeting dihydrofolate reductase makes it irreplaceable for certain indications [5].

Regulatory Environment

The drug’s regulatory status remains stable. The FDA classifies Daraprim as an essential medicine, facilitating continued manufacturing. No recent generic approvals threaten market stability, though potential biosimilars remain unlikely given the drug’s chemical nature and patent status.

Market Projections

Short-Term Outlook (1-3 Years)

• Stable Demand: Driven by ongoing treatment needs in immunocompromised populations.
• Pricing Pressures: Limited alternative therapies and high treatment complexity sustain current pricing levels.
• Innovative Uses: Small but growing research into Daraprim’s utility in combination therapies and resistant strains may marginally boost demand.

Medium to Long-Term Outlook (4-10 Years)

• Emerging Treatments: Development of targeted immunotherapies or gene-based approaches might gradually diminish reliance on Daraprim.
• Biosimilar/Chemical Alternatives: Introduction of generics could lower costs but face regulatory hurdles given the complexity of chemical manufacturing.
• Resistance and New Indications: The emergence of resistant Plasmodium strains could extend Daraprim’s market by positioning it as a second-line agent, especially if existing therapies fail.

Market Growth Potential

Estimates suggest a compound annual growth rate (CAGR) of approximately 1-3% in niche markets over the next decade, primarily driven by demographic factors like increasing immunosuppressed populations worldwide.

Strategic Considerations for Stakeholders

• Pharmaceutical Manufacturers: Focus on securing supply chains and exploring formulations that improve tolerability.
• Investors: Monitor developments in combination protocols and resistance patterns that could alter market share.
• Healthcare Providers: Stay informed of emerging therapies, dosing strategies, and safety data to optimize treatment regimens.
• Regulators: Encourage research into long-term safety and resistance management.

Key Takeaways

• Daraprim remains critical in the treatment of toxoplasmosis and certain malaria cases, especially for immunocompromised patients.
• Limited but ongoing clinical trials focus on optimizing dosing, combination therapy, and exploring new indications.
• Market demand is stable within niche segments but faces challenges from emerging treatments and potential generics.
• The upcoming decade may see slight market growth, driven by resistance issues and demographic shifts in vulnerable populations.
• Stakeholders should monitor clinical research developments and resistance trends to adapt strategies accordingly.

FAQs

Q1: What is the current status of Daraprim in clinical trials?

A1: Daraprim is involved in limited clinical trials mainly focusing on combination therapies, dosing optimization, and resistance management, with no large-scale phase III trials currently active.

Q2: How does market competition impact Daraprim’s pricing?

A2: With no recent generics approved and limited alternatives, Daraprim’s pricing remains high, though price stability post-2015 has somewhat alleviated controversy. Competition from other drugs is minimal for its primary indications.

Q3: Are there any new indications for Daraprim on the horizon?

A3: Research exploring Daraprim’s role in treating drug-resistant malaria and as part of combination therapy for toxoplasmosis is underway, though these are not yet approved for widespread clinical use.

Q4: What are the main challenges facing Daraprim’s future market?

A4: Challenges include the development of resistance, competing therapies, regulatory hurdles for generics or biosimilars, and the need for more comprehensive clinical data to support new uses.

Q5: How might emerging therapies affect Daraprim’s market share?

A5: Advances such as targeted immunotherapies, gene-editing techniques, or newer antiparasitic agents could reduce reliance on Daraprim over time, especially if they demonstrate superior efficacy or safety profiles.

Sources

[1] ClinicalTrials.gov. Pyrimethamine in Toxoplasmosis. Retrieved from [Link].

[2] WHO Malaria Reports. Emerging Use Cases for Pyrimethamine. Retrieved from [Link].

[3] Journal of Infectious Diseases. Combination Therapy in Toxoplasmosis. Retrieved from [Link].

[4] Reuters. Daraprim Pricing and Market Dynamics. Retrieved from [Link].

[5] FDA Drug Database. Daraprim (pyrimethamine) Summary. Retrieved from [Link].

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This report aims to inform stakeholders on Daraprim's current research landscape, market status, and future outlook, integrating clinical trial insights with market analysis for strategic decision-making.