CLINICAL TRIALS PROFILE FOR AMPHOTERICIN B

505(b)(2) Clinical Trials for Amphotericin B

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 Dosage	NCT00421187 ↗	Ambisome and Management of Culture-negative Neutropenic Fever Unresponsive to Antibiotics	Terminated	Gilead Sciences	Phase 4	2007-03-01	Administration of a single high dose (10 mg/kg) of AmBisome® no later than 72 hours after ARNF onset followed by two 5 mg/kg doses on days 2 and 5 may provide sustained tissue levels of amphotericin B that are as mycologically effective as those provided after administering the standard daily dose of 3 mg/kg/day. The new dosing regimen is anticipated to be equally clinically effective compared with the standard AmBisome® regimen when given for the duration of neutropenic fever in patients with ARNF. In addition, the degree and incidence of nephrotoxicity are predicted to be lower with the 3 sequential dose regimen compared to daily dosing with 3 mg/kg because of the lower cumulative dosage (20 mg/kg versus 42 mg/kg, respectively), which is 1 contributing factor for the development of acute renal failure. Furthermore, the lower cumulative dose may be a cost-effective strategy for the treatment of patients with ARNF.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Institutul Clinic Fundeni	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.
New Dosage	NCT02372357 ↗	A New Dosing Regimen for Posaconazole Prophylaxis in Children Based on Body Surface Area	Completed	Institutul Clinic Fundeni Bucharest	Phase 4	2012-02-01	A new prophylactic posaconazole dosing regimen of 120mg/m² tid is evaluated pharmacologically in children 13 years and younger, suffering from a hematologic malignancy.

All Clinical Trials for Amphotericin B

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00000639 ↗	A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis	Completed	Washington University School of Medicine	N/A	1969-12-31	To evaluate the effectiveness and safety of amphotericin B plus flucytosine (5-fluorocytosine) compared to amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and to compare the effectiveness and safety of fluconazole versus itraconazole. At least 10 percent of patients with a low CD4 count and HIV infection will develop meningitis due to Cryptococcus neoformans. More effective treatments than the standard therapy need to be explored.
NCT00000639 ↗	A Randomized Double Blind Protocol Comparing Amphotericin B With Flucytosine to Amphotericin B Alone Followed by a Comparison of Fluconazole and Itraconazole in the Treatment of Acute Cryptococcal Meningitis	Completed	National Institute of Allergy and Infectious Diseases (NIAID)	N/A	1969-12-31	To evaluate the effectiveness and safety of amphotericin B plus flucytosine (5-fluorocytosine) compared to amphotericin B alone for a first episode of acute cryptococcal meningitis in AIDS patients, and to compare the effectiveness and safety of fluconazole versus itraconazole. At least 10 percent of patients with a low CD4 count and HIV infection will develop meningitis due to Cryptococcus neoformans. More effective treatments than the standard therapy need to be explored.
NCT00000677 ↗	SCH 39304 as Therapy for Acute Cryptococcal Meningitis in HIV-Infected Patients Followed by Maintenance Therapy	Completed	Schering-Plough	Phase 1	1969-12-31	To assess the safety and effectiveness of SCH 39304 as primary treatment of acute cryptococcal meningitis in HIV-infected patients. Safety and effectiveness of maintenance therapy following successful treatment of acute disease are also evaluated. Cryptococcal meningitis is a significant cause of illness and death in HIV-infected patients. Intravenous amphotericin B is effective for acute disease but relapse occurs in the majority of patients. Maintenance therapy is recommended but must be balanced against the multiple toxicities of the drugs used and the problems associated with the weekly administration of intravenous therapy. Treatments that are equally or more effective and less toxic than traditional methods are needed, especially oral therapy. SCH 39304 is an orally active antifungal drug that in animal studies is active against a wide range of systemic fungal infections including infections due to Cryptococcus. Features of SCH 39304 suggest that it might be of value in the treatment of cryptococcal meningitis.

Clinical Trial Conditions for Amphotericin B

Condition Name

Condition Name for Amphotericin B
Intervention	Trials
HIV Infections	25
Cryptococcal Meningitis	16
Visceral Leishmaniasis	13

Condition MeSH

Condition MeSH for Amphotericin B
Intervention	Trials
Meningitis, Cryptococcal	30
Meningitis	30
Mycoses	28

Clinical Trial Locations for Amphotericin B

Trials by Country

Trials by Country for Amphotericin B
Location	Trials
United States	354
India	21
China	17
Canada	15
Brazil	14

Trials by US State

Trials by US State for Amphotericin B
Location	Trials
California	25
New York	23
Texas	23
Pennsylvania	21
Florida	18

Clinical Trial Progress for Amphotericin B

Clinical Trial Phase

Clinical Trial Phase for Amphotericin B
Clinical Trial Phase	Trials
Phase 4	29
Phase 3	45
Phase 2/Phase 3	7

Clinical Trial Status

Clinical Trial Status for Amphotericin B
Clinical Trial Phase	Trials
Completed	108
Terminated	15
Unknown status	13

Clinical Trial Sponsors for Amphotericin B

Sponsor Name

Sponsor Name for Amphotericin B
Sponsor	Trials
National Institute of Allergy and Infectious Diseases (NIAID)	17
Pfizer	13
Gilead Sciences	10

Sponsor Type

Sponsor Type for Amphotericin B
Sponsor	Trials
Other	183
Industry	85
NIH	23

Amphotericin B: Clinical Trials, Market Analysis, and Projections

Last updated: January 1, 2025

Introduction

Amphotericin B is a potent antifungal medication used to treat a variety of fungal infections, including those caused by Aspergillus, Candida, and Cryptococcus species. This article will delve into recent clinical trials, market analysis, and future projections for this critical drug.

Recent Clinical Trials

AMBITION-cm Trial

One of the most significant recent trials is the AMBITION-cm trial, conducted in 2022. This trial compared a single high-dose regimen of liposomal amphotericin B (10 mg/kg) plus daily flucytosine and fluconazole for 2 weeks against the traditional WHO-recommended regimen of amphotericin B deoxycholate with flucytosine for 1 week, followed by fluconazole for 1 week. The results showed that the single-dose liposomal amphotericin B regimen was noninferior to the traditional regimen, making it a preferred option for HIV-related cryptococcal meningitis[1].

Adoption and Barriers

Despite the promising results, the adoption of the AMBITION-cm regimen in high-resource settings has been slow. A survey of physicians revealed that only about 14% had used this regimen, with the majority citing concerns about the applicability of trials conducted in low-resource settings and the lack of recommendation in older guidelines[1].

Other Formulations

Research is also ongoing into new formulations of amphotericin B to reduce toxicity and improve efficacy. For example, MAT2203, an oral lipid nanocrystal formulation of amphotericin B, has shown promising results in treating deep tissue infections with lower toxicity compared to traditional intravenous formulations[5].

Market Analysis

Current Market Size and Growth

The global amphotericin B market was valued at USD 0.22 billion in 2022 and is projected to grow to USD 0.30 billion by 2030, with a Compound Annual Growth Rate (CAGR) of 4.6% during the forecast period of 2023-2030[2].

Drivers of Market Growth

Several factors are driving the growth of the amphotericin B market:

• Increase in Fungal Infections: The rising incidence of fungal infections, particularly among immunocompromised individuals and those with chronic diseases, is a significant driver.
• Hospital-Acquired Infections: The increase in hospital-acquired infections (HAIs) also contributes to the demand for antifungal medications like amphotericin B.
• Emerging Markets and Healthcare Expenditure: Growing healthcare expenditure and government initiatives in emerging markets are further boosting the market[2].

Market Segmentation

The global amphotericin B market is segmented by product type, application, route of administration, drug class, end-users, and distribution channel. Key segments include:

• Product Type: Static drops, atomization inhalation, local lesion injection, and others.
• Application: Vaginitis, candida infection, leishmaniasis, kala-azar, cryptococcal infection, aspergillus infection, and others.
• Route of Administration: Intravenous, parenteral, oral, and others.
• Drug Class: Antifungals, systemic, and others.
• End-Users: Clinics, hospitals, and others.
• Distribution Channel: Hospital pharmacy, retail pharmacy, online pharmacy, and others[2].

Market Dynamics

Drivers

• Rise in Fungal Infections: The increasing incidence of fungal infections globally is a major driver.
• Growing Healthcare Expenditure: Increased healthcare spending and government initiatives are supporting market growth.
• Emerging Markets: Expanding healthcare infrastructure in emerging markets is another key factor[2].

Challenges

• Side Effects: Common side effects of amphotericin B, such as nephrotoxicity, seizures, and gastrointestinal issues, can limit its use.
• Drug Resistance: The emergence of drug-resistant fungal strains poses a significant challenge.
• Regulatory Frameworks: Variations in regulatory approvals and guidelines can affect market adoption of new regimens[2].

Cost and Budget Impact Analysis

Liposomal Amphotericin B vs. Amphotericin B Lipid Complex

A cost-minimization and budget impact analysis comparing liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) found that L-AMB can offer significant cost savings due to lower rates of adverse events. The study estimated that switching from ABLC to L-AMB could result in a 3.8% cost reduction, translating to an absolute cost savings of $61,191 for a hypothetical hospital with 100 annual admissions[3].

Future Projections

Epidemiological Changes

The epidemiology of fungal infections is expected to continue changing, with new populations at risk. Early diagnosis and appropriate treatment will remain crucial, and broad-spectrum antifungal agents like liposomal amphotericin B will be essential in managing these infections[4].

New Formulations and Technologies

Advancements in drug delivery technologies, such as the oral lipid nanocrystal formulation (MAT2203), are expected to improve patient outcomes by reducing toxicity and enhancing compliance. These innovations will likely drive further growth in the amphotericin B market[5].

Regulatory and Clinical Updates

Future updates to clinical guidelines, such as the incorporation of the AMBITION-cm regimen into standard recommendations, will influence market trends. Ongoing research and clinical trials will continue to shape the therapeutic landscape for amphotericin B[1].

Key Takeaways

• Clinical Trials: The AMBITION-cm trial has established a single-dose liposomal amphotericin B regimen as a noninferior option for treating cryptococcal meningitis.
• Market Growth: The global amphotericin B market is expected to grow from USD 0.22 billion in 2022 to USD 0.30 billion by 2030, driven by increasing fungal infections and healthcare expenditure.
• Market Dynamics: The market is influenced by factors such as the rise in hospital-acquired infections, emerging markets, and the development of new formulations.
• Cost Analysis: Liposomal amphotericin B offers cost savings compared to other formulations due to lower adverse event rates.
• Future Projections: The market will be shaped by epidemiological changes, new drug delivery technologies, and updates to clinical guidelines.

FAQs

What is the current recommended treatment for cryptococcal meningitis involving amphotericin B?

The WHO now recommends a single high-dose liposomal amphotericin B (10 mg/kg) on day 1 plus 14 days of flucytosine and fluconazole as the preferred regimen for HIV-related cryptococcal meningitis[1].

What are the main drivers of the global amphotericin B market?

The main drivers include the rise in fungal infections, growing healthcare expenditure, and emerging markets[2].

What are the common side effects of amphotericin B?

Common side effects include nephrotoxicity, seizures, abdominal pain, numbness, fever, and gastrointestinal issues[2].

How does liposomal amphotericin B compare to amphotericin B lipid complex in terms of cost?

Liposomal amphotericin B can offer significant cost savings due to lower rates of adverse events compared to amphotericin B lipid complex[3].

What new formulations of amphotericin B are being developed?

One notable development is MAT2203, an oral lipid nanocrystal formulation of amphotericin B, which has shown promising results in reducing toxicity and improving patient compliance[5].

Sources

1. Infectious Diseases Physician Management of Cryptococcal Meningitis - Oxford Academic
2. Global Amphotericin B Market Size, Demand & Revenue Forecast By 2030 - Data Bridge Market Research
3. Budget impact analysis of liposomal amphotericin B and amphotericin B lipid complex - PubMed
4. Liposomal amphotericin B—the future - Oxford Academic
5. Oral Lipid Nanocrystal Amphotericin B (MAT2203) for the Treatment of Deep Tissue Infections - Oxford Academic