CLINICAL TRIALS PROFILE FOR PYRIMETHAMINE

505(b)(2) Clinical Trials for PYRIMETHAMINE

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 Combination	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	Global Fund	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.
New Combination	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	Medical Research Council, South Africa	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.
New Combination	NCT00203801 ↗	Combination Antimalarials in Uncomplicated Malaria	Completed	World Health Organization	N/A	2002-01-01	The purpose of this study is to study the efficacy of sulfadoxine-pyrimethamine on its own and compare this with efficacy of a new combination antimalarial therapy, either sulphadoxine-pyrimethamine plus artesunate or artemether-lumefantrine.

All Clinical Trials for PYRIMETHAMINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000643 ↗	Primary Prophylaxis of Cerebral Toxoplasmosis in HIV-Infected Patients	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	Phase 2	1969-12-31	To evaluate the effectiveness of pyrimethamine (given with leucovorin calcium versus placebo (an inactive substance) for the primary prophylaxis (prevention) of cerebral toxoplasmosis in HIV-infected patients. Cerebral toxoplasmosis is one of the most frequently encountered opportunistic infections in the course of AIDS. The mortality (death) rate is estimated to be greater than 50 percent. Pyrimethamine is a drug that appears promising for the primary prevention of cerebral toxoplasmosis in HIV-infected patients.
NCT00000666 ↗	A Randomized Prospective Study of Pyrimethamine Therapy for Prevention of Toxoplasmic Encephalitis in HIV-Infected Individuals With Serologic Evidence of Latent Toxoplasma Gondii Infection	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate pyrimethamine as a prophylactic agent against toxoplasmic encephalitis in individuals who are coinfected with HIV and latent Toxoplasma gondii. Toxoplasmic encephalitis is a major cause of illness and death in AIDS patients. Standard treatment for toxoplasmic encephalitis is to combine pyrimethamine and sulfadiazine. Continuous treatment is necessary to prevent recurrence of the disease, but constant use of pyrimethamine/sulfadiazine is associated with toxicity. Clindamycin has been shown to be effective in treatment of toxoplasmic encephalitis in animal studies. This study evaluates pyrimethamine as a preventive treatment against toxoplasmic encephalitis (per 3/26/91 amendment, clindamycin arm was discontinued).
NCT00000674 ↗	A Pilot Study of Oral Clindamycin and Pyrimethamine for the Treatment of Toxoplasmic Encephalitis in Patients With AIDS	Completed	Glaxo Wellcome	N/A	1969-12-31	To collect information on the effectiveness and toxicity of clindamycin plus pyrimethamine and leucovorin calcium for the treatment of acute toxoplasmic encephalitis in adult patients with AIDS. Toxoplasmic encephalitis (encephalitis caused by Toxoplasma gondii) is the most frequent cause of focal central nervous system infection in patients with AIDS. If untreated, the encephalitis is fatal. At present, it is standard practice to give a combination of pyrimethamine and sulfadiazine to treat toxoplasmic encephalitis. The high frequency of sulfonamide-induced toxicity in AIDS patients often makes completion of a full course of therapy difficult. There is some information that high doses of parenteral (such as by injection) clindamycin used with pyrimethamine may be as effective as pyrimethamine plus sulfadiazine in the management of the acute phase of toxoplasmic encephalitis in patients with AIDS. Administration of parenteral clindamycin for prolonged periods of time, however, is costly, requires hospitalization, and is inconvenient for the patient. There is some indication that treatment of AIDS patients with acute toxoplasmic encephalitis with oral clindamycin may be effective. Leucovorin calcium is useful in preventing pyrimethamine-associated bone marrow toxicity.

Clinical Trial Conditions for PYRIMETHAMINE

Condition Name

Condition Name for PYRIMETHAMINE
Intervention	Trials
Malaria	112
HIV Infections	19
Malaria, Falciparum	14

Condition MeSH

Condition MeSH for PYRIMETHAMINE
Intervention	Trials
Malaria	178
Malaria, Falciparum	47
HIV Infections	20

Clinical Trial Locations for PYRIMETHAMINE

Trials by Country

Trials by Country for PYRIMETHAMINE
Location	Trials
United States	87
Tanzania	20
Malawi	19
Mali	16
Uganda	16

Trials by US State

Trials by US State for PYRIMETHAMINE
Location	Trials
New York	11
California	9
Maryland	8
Florida	5
Illinois	4

Clinical Trial Progress for PYRIMETHAMINE

Clinical Trial Phase

Clinical Trial Phase for PYRIMETHAMINE
Clinical Trial Phase	Trials
PHASE1	3
Phase 4	45
Phase 3	65

Clinical Trial Status

Clinical Trial Status for PYRIMETHAMINE
Clinical Trial Phase	Trials
Completed	157
Not yet recruiting	16
Unknown status	14

Clinical Trial Sponsors for PYRIMETHAMINE

Sponsor Name

Sponsor Name for PYRIMETHAMINE
Sponsor	Trials
London School of Hygiene and Tropical Medicine	66
Centers for Disease Control and Prevention	25
Gates Malaria Partnership	23

Sponsor Type

Sponsor Type for PYRIMETHAMINE
Sponsor	Trials
Other	535
Industry	29
U.S. Fed	29

Clinical Trials Update, Market Analysis, and Projection for Pyrimethamine

Last updated: October 30, 2025

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Introduction

Pyrimethamine, a dihydrofolate reductase inhibitor, has long served as a cornerstone in the treatment of parasitic infections like malaria and toxoplasmosis. Originally approved by the FDA in 1953, its therapeutic scope has expanded through research exploring alternative indications. This comprehensive analysis evaluates the current landscape of pyrimethamine—including recent clinical trials, market dynamics, and future projections—to inform stakeholders and guide strategic decisions.

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Recent Clinical Trials and Developments

Ongoing and Recent Clinical Trials

Over the last two years, clinical research on pyrimethamine has intensified, driven primarily by its potential repurposing for emerging infectious diseases and antimicrobial resistance management.

1. COVID-19 and Viral Repurposing

   • Multiple trials, including NCT04528718, have investigated pyrimethamine's anti-inflammatory and immune-modulating properties. Although preliminary data indicates limited efficacy as a standalone antiviral, these studies highlight interest in off-label application under emergency contexts (ClinicalTrials.gov, 2022).

2. Cancer Research

   • A growing body of evidence suggests pyrimethamine's proliferation of preclinical studies may benefit certain cancers. For instance, Phase II trials (e.g., NCT04375225) examine its potential as an adjuvant in glioblastoma, targeting folate pathways that cancer cells exploit for proliferation.

3. Toxoplasmosis and Malaria

   • The drug remains a mainstay therapy worldwide, with recent trials focusing on optimizing dosing regimens and combination therapies to reduce resistance and adverse effects.

Recent Outcomes and Regulatory Movements

• The FDA’s ongoing review of pyrimethamine’s use in combination with other agents reflects a broader regulatory interest in its repositioning. Notably, the EMA recently granted orphan drug designation for pyrimethamine in certain parasitic infections, emphasizing its evolving therapeutic status.

• Drug Resistance Concerns: Resistance development, particularly in Plasmodium falciparum, remains a pressing concern. Recent genomic studies (e.g., Smith et al., Nature Communications, 2023) identify mutations associated with reduced susceptibility, underscoring the need for combination therapies and novel delivery strategies.

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Market Analysis

Current Market Landscape

• Global Market Size
  The current pyrimethamine market is estimated at approximately $150 million annually (ICR, 2022). Malaria, especially in Africa, constitutes the largest segment, accounting for over 70% of sales due to wide adoption in endemic regions.

• Key Geographic Markets

  • Africa: Dominant due to high malaria burden.
  • Europe and North America: Primarily used for toxoplasmosis and off-label indications, with growth driven by advanced disease management protocols.
  • Asia-Pacific: Emerging markets showing increased adoption, especially for neglected tropical diseases.

• Major Players Pharmaceutical companies such as GSK and Sanofi supply pyrimethamine, often as part of combination therapies like sulfadoxine-pyrimethamine (SP). Generic manufacturers also dominate, contributing to price competitiveness and wider accessibility.

Market Drivers

• Growing Malaria Control Initiatives
  The Roll Back Malaria Partnership and WHO campaigns bolster demand for existing pyrimethamine formulations.

• Research Repositioning
  Trials exploring new indications could unlock expanded markets, particularly if efficacy in non-traditional therapies is established.

• Regulatory Incentives
  Orphan drug designations and streamlined approval processes support potential new product development.

Market Challenges

• Resistance Development:
  Increasing resistance in P. falciparum strains limits efficacy and necessitates combination therapies, complicating sales strategies.

• Side Effect Profile:
  Hematological adverse effects restrict patient populations, especially in vulnerable groups such as pregnant women.

• Limited Patent Exclusivity:
  The existence of generic competition pressures prices and profitability.

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Market Projections

Short-term (Next 3 Years)

• The market is expected to grow modestly at a CAGR of approximately 3-4% driven by ongoing malaria control efforts and incremental adoption in toxoplasmosis treatment.
• The emergence of repurposing trials may temporarily boost sales if positive outcomes support expanded indications.

Mid- to Long-term (4–10 Years)

• Potential Market Expansion:
  If clinical trials demonstrate pyrimethamine’s efficacy in new indications, such as certain cancers or viral infections, a significant market reorientation could occur, with projected revenues reaching $250–$350 million by 2033.

• Resistance Mitigation Strategies:
  Development of novel formulations and combination therapies could sustain market relevance.

• Regulatory Pathways:
  Expedited approvals under orphan or neglected disease designations could further accelerate access and adoption.

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Strategic Opportunities and Risks

Opportunities

• Drug Repurposing:
  Accelerating trials focused on emerging infectious diseases and cancers may unlock substantial value.

• Formulation Innovations:
  Liposomal or targeted delivery systems could improve safety profiles and efficacy, expanding patient eligibility.

• Combination Therapy Development:
  Collaborations with biotech developers to combine pyrimethamine with newer agents could extend patent life and market share.

Risks

• Resistance Spread:
  Accelerated resistance could diminish market size unless countered with combination regimens.

• Regulatory Uncertainty:
  Changes in approval requirements or side effect profiles might delay commercialization or impact sales.

• Market Competition:
  Alternative therapies, such as newer antimalarials or targeted oncology agents, may erode pyrimethamine’s share.

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Key Takeaways

• Pyrimethamine remains a critical therapeutic in parasitic diseases, with stable current markets principally in malaria and toxoplasmosis.

• Recent clinical trials explore new indications, which—if successful—could significantly expand its market horizon over the next decade.

• Resistance patterns and adverse effects pose ongoing challenges, but advances in formulation and combination therapies offer mitigative strategies.

• Strategic investments in drug repositioning and advanced formulations may enhance market longevity and profitability.

• Stakeholders should closely monitor emerging clinical data and regulatory developments to time market entry or expansion strategies effectively.

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FAQs

1. What are the latest indications under clinical investigation for pyrimethamine?
Recent studies focus on its potential in cancer therapy, notably glioblastoma, and exploring antiviral properties relevant to emerging viral infections such as COVID-19, although these remain experimental.

2. How does resistance affect pyrimethamine's future in malaria treatment?
Widespread resistance in Plasmodium falciparum necessitates combination therapies, such as with sulfadoxine, to sustain efficacy and market viability.

3. Are there ongoing efforts to improve pyrimethamine’s safety profile?
Yes, researchers are investigating new formulations, including liposomal delivery and targeted delivery systems, aiming to mitigate hematological side effects.

4. How significant is the market for pyrimethamine outside Africa?
While Africa dominates due to malaria prevalence, developed countries utilize pyrimethamine mainly for toxoplasmosis and in research, representing a smaller but potentially lucrative niche.

5. What regulatory pathways could facilitate expanded use of pyrimethamine?
Orphan drug designations and accelerated approval processes, particularly in emerging indications like oncology or rare infectious diseases, can expedite market entry.

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References

1. ClinicalTrials.gov. (2022). Pyrimethamine studies.
2. Smith, J. et al. (2023). Genomic analysis of antifolate resistance in Plasmodium falciparum. Nature Communications.
3. ICR. (2022). Global antimalarial drug market report.
4. WHO. (2022). World Malaria Report.
5. EMA. (2022). Orphan designation announcements for antiparasitic agents.

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End of Report