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.

Clinical Trial Conditions for DARAPRIM

Condition Name

Condition Name for DARAPRIM
Intervention	Trials
Familial Amyotrophic Lateral Sclerosis	1
Head and Neck Cancer	1
Healthy	1

Condition MeSH

Condition MeSH for DARAPRIM
Intervention	Trials
Motor Neuron Disease	1
Carcinoma, Squamous Cell	1
Depressive Disorder	1

Clinical Trial Locations for DARAPRIM

Trials by Country

+

−

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Withdrawn	1

Clinical Trial Sponsors for DARAPRIM

Sponsor Name

Sponsor Name for DARAPRIM
Sponsor	Trials
Montefiore Medical Center	2
Stanley Medical Research Institute	1
University of Kansas Medical Center	1

Sponsor Type

Sponsor Type for DARAPRIM
Sponsor	Trials
Other	15
NIH	1

Daraprim: Clinical Trials, Market Analysis, and Projections

Introduction

Daraprim, also known as pyrimethamine, is a crucial medication in the treatment of toxoplasmosis, a parasitic infection that can be life-threatening for individuals with compromised immune systems, such as those with HIV/AIDS. This article delves into the clinical trials, market analysis, and projections for Daraprim, highlighting its significance, pricing controversies, and regulatory developments.

Clinical Use and Mechanism

Daraprim is a folic acid antagonist that, when used in conjunction with sulfonamides, effectively treats toxoplasmosis. It has been shown to kill proliferative Toxoplasmas both in vivo and in vitro[1][4].

Clinical Trials and Pharmacology

Clinical studies on Daraprim have focused on optimizing its therapeutic regimen to achieve high serum concentrations while minimizing toxicity. For instance, a study involving 19 patients treated with pyrimethamine and sulfonamides aimed to determine the optimal dosing to rapidly achieve high serum concentrations and assess the relationship between serum levels and bone marrow toxicity[1].

FDA Approved Indications

Daraprim is FDA-approved for the treatment of toxoplasmosis when used with a sulfonamide. It is no longer indicated for the treatment or chemoprophylaxis of malaria as of June 2017[4].

Pricing Controversies

One of the most significant issues surrounding Daraprim is its dramatic price increase. In August 2015, Turing Pharmaceuticals (later known as Vyera Pharmaceuticals) acquired the rights to Daraprim and raised the price per tablet from $13.50 to $750, a 5,000% increase. This move was widely criticized by medical professionals, patient advocacy groups, and regulatory bodies, who deemed it unjustifiable and unsustainable for the healthcare system[2][5].

Regulatory Actions

The Federal Trade Commission (FTC) and six state attorneys general filed a lawsuit against Martin Shkreli and Vyera Pharmaceuticals, alleging an illegal scheme to maintain a monopoly over Daraprim. The lawsuit resulted in a landmark victory for the regulators, highlighting their commitment to policing anti-competitive behavior that increases healthcare costs or decreases access to critical medications[5].

Market Analysis

The market for Daraprim is part of the broader pharmaceutical market, which is influenced by various factors including regulatory changes, patient demand, and competitive dynamics.

Market Size and Growth

While Daraprim itself is a niche product, it is part of a larger pharmaceutical market. The global clinical trials market, which includes drugs like Daraprim, is expected to grow significantly. By 2030, the global clinical trials market is projected to reach around $95 billion, up from $51.78 billion in 2022, with a Compound Annual Growth Rate (CAGR) of 7.07% during the forecast period[3].

Regional Market

North America dominated the global clinical trials market in 2021, accounting for 50.7% of the market share. However, the Asia Pacific region is anticipated to grow at the fastest CAGR of 6.8% over the forecast period[3].

Segment Analysis

The oncology segment accounted for the largest revenue share in the global clinical trials market in 2021, with 23.5%, and is expected to witness the fastest CAGR of 6.3% over the forecast period. This indicates a broader trend in pharmaceutical research and development, though Daraprim specifically falls under the category of infectious diseases[3].

Impact of Pricing on Access

The drastic price increase of Daraprim has had significant implications for patient access. The Infectious Diseases Society of America and the HIV Medicine Association have expressed concerns that such price hikes are unsustainable for the healthcare system and unjustifiable for medically vulnerable patient populations[2].

Future Projections

Given the regulatory scrutiny and public backlash against price gouging, it is likely that the pricing strategy for Daraprim will be reevaluated. The FTC's victory in the lawsuit against Vyera Pharmaceuticals sets a precedent for regulatory action against similar price hikes in the future.

Competitive Landscape

The pharmaceutical industry is highly competitive, and companies are under increasing pressure to justify price increases. The case of Daraprim serves as a cautionary tale for pharmaceutical companies considering significant price hikes for essential medications.

Technological and Regulatory Trends

Advancements in digital health and the COVID-19 pandemic have accelerated clinical trials and regulatory approvals. The FDA's Coronavirus Treatment Acceleration Program (CTAP) is an example of how regulatory bodies are working to bring new treatments to patients quickly. These trends could influence the development and pricing of future medications, including those for toxoplasmosis[3].

Key Takeaways

• Clinical Use: Daraprim is a critical medication for treating toxoplasmosis, especially in immunocompromised patients.
• Pricing Controversy: The drug's price was increased by 5,000% in 2015, sparking widespread criticism and regulatory action.
• Regulatory Actions: The FTC and state attorneys general successfully sued Vyera Pharmaceuticals for maintaining a monopoly over Daraprim.
• Market Analysis: The global clinical trials market is growing, with significant regional and segmental variations.
• Future Projections: Regulatory scrutiny and public pressure are likely to influence pricing strategies for essential medications like Daraprim.

FAQs

What is Daraprim used for?

Daraprim (pyrimethamine) is used for the treatment of toxoplasmosis, particularly in conjunction with sulfonamides, and is crucial for patients with compromised immune systems.

Why did the price of Daraprim increase so dramatically?

The price of Daraprim increased by 5,000% in 2015 after Turing Pharmaceuticals (later Vyera Pharmaceuticals) acquired the rights to the drug, citing that the drug was previously undervalued.

What regulatory actions were taken against the price hike of Daraprim?

The FTC and six state attorneys general filed a lawsuit against Vyera Pharmaceuticals and Martin Shkreli, alleging an illegal scheme to maintain a monopoly over Daraprim, resulting in a landmark victory for the regulators.

How does the global clinical trials market impact Daraprim?

The global clinical trials market growth indicates an increasing focus on pharmaceutical research and development, which could influence the development and pricing of future medications, including those for toxoplasmosis.

What are the implications of the Daraprim price hike on patient access?

The significant price increase has made Daraprim less accessible to patients, particularly those with compromised immune systems, and has been criticized by medical professionals and patient advocacy groups.

Sources

1. Pharmacological Studies of Pyrimethamine (Daraprim) in Man - JAMA Ophthalmology
2. Turing Daraprim Price Hike Follows a Precedent - Pharmacy Times
3. Clinical Trials Market is Rising Rapidly Up to USD 95 BN by 2030 - BioSpace
4. Clinical Policy: Pyrimethamine (Daraprim) - Superior HealthPlan
5. FTC and Bipartisan State AGs Win Landmark Case Against 'Pharma Bro' Martin Shkreli Over Daraprim Monopoly - Regulatory Oversight