CLINICAL TRIALS PROFILE FOR MILTEFOSINE

All Clinical Trials for MILTEFOSINE

Trial ID	Title	Status	Sponsor	Phase	Start Date	Summary
NCT00233545 ↗	Miltefosine to Treat Cutaneous Leishmaniasis in Bolivia	Completed	AB Foundation	Phase 2	2005-09-01	Cutaneous leishmaniasis is typically treated with the parenteral product pentavalent antimony. Miltefosine is an oral agent shown to be active for mucosal leishmaniasis due to L braziliensis in Bolivia and cutaneous leishmaniasis due to L panamensis in Colombia. This trial is intended to evaluate miltefosine for cutaneous leishmaniasis due to L braziliensis in Bolivia. Patients will be randomly assigned to miltefosine or pentavalent antimony. Standard dose regimens will be used for both drugs.
NCT00317629 ↗	Controlled Nitric Oxide Releasing Patch Versus Meglumine Antimoniate in the Treatment of Cutaneous Leishmaniasis	Terminated	Secretaria de Salud de Santander	Phase 3	2006-05-01	Cutaneous leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be administered daily and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In the case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.
NCT00317629 ↗	Controlled Nitric Oxide Releasing Patch Versus Meglumine Antimoniate in the Treatment of Cutaneous Leishmaniasis	Terminated	Secretaria de Salud de Tolima	Phase 3	2006-05-01	Cutaneous leishmaniasis is a worldwide disease, endemic in 88 countries, that has shown an increasing incidence over the last two decades. So far, pentavalent antimony compounds have been considered the treatment of choice, with a percentage of cure of about 85%. However, the high efficacy of these drugs is counteracted by their many disadvantages and adverse events. Previous studies have shown nitric oxide to be a potential alternative treatment when administered topically with no serious adverse events. However, due to the unstable nitric oxide release, the topical donors needed to be applied frequently, making the adherence to the treatment difficult. The electrospinning technique has allowed the production of a multilayer transdermal patch that produces a continuous and stable nitric oxide release. The main objective of this study is to evaluate this novel nitric oxide topical donor for the treatment of cutaneous leishmaniasis. A double-blind, randomized, double-masked, placebo-controlled clinical trial, including 620 patients from endemic areas for leishmaniasis in Colombia was designed to investigate whether this patch is as effective as meglumine antimoniate for the treatment of cutaneous leishmaniasis but with less adverse events. Subjects with ulcers characteristic of cutaneous leishmaniasis will be medically evaluated and laboratory tests and parasitological confirmation performed. After checking the inclusion/exclusion criteria, the patients will be randomly assigned to one of two groups. During 20 days Group 1 will receive simultaneously meglumine antimoniate and placebo of nitric oxide patches while Group 2 will receive placebo of meglumine antimoniate and active nitric oxide patches. During the treatment visits, the medications will be administered daily and the presence of adverse events assessed. During the follow-up, the research group will visit the patients at days 21, 45, 90 and 180. The healing process of the ulcer, the health of the participants, recidivisms and/or reinfection will also be assessed. The evolution of the ulcers will be photographically registered. In the case that the effectiveness of the patches is demonstrated, a novel and safe therapeutic alternative for one of the most important public health problems in many countries will be available to patients.

Clinical Trial Conditions for MILTEFOSINE

Condition Name

Condition Name for MILTEFOSINE
Intervention	Trials
Cutaneous Leishmaniasis	13
Visceral Leishmaniasis	7
Leishmaniasis	6

Condition MeSH

Condition MeSH for MILTEFOSINE
Intervention	Trials
Leishmaniasis	43
Leishmaniasis, Cutaneous	22
Leishmaniasis, Visceral	13

Clinical Trial Locations for MILTEFOSINE

Trials by Country

Trials by Country for MILTEFOSINE
Location	Trials
Bolivia	13
Brazil	12
Colombia	8
Sudan	5
India	5

Trials by US State

Trials by US State for MILTEFOSINE
Location	Trials
Maryland	3
Texas	1

Clinical Trial Progress for MILTEFOSINE

Clinical Trial Phase

Clinical Trial Phase for MILTEFOSINE
Clinical Trial Phase	Trials
PHASE3	1
PHASE2	2
PHASE1	1

Clinical Trial Status

Clinical Trial Status for MILTEFOSINE
Clinical Trial Phase	Trials
Completed	31
RECRUITING	5
Terminated	4

Clinical Trial Sponsors for MILTEFOSINE

Sponsor Name

Sponsor Name for MILTEFOSINE
Sponsor	Trials
Drugs for Neglected Diseases	11
AB Foundation	6
Knight Therapeutics (USA) Inc	5

Sponsor Type

Sponsor Type for MILTEFOSINE
Sponsor	Trials
Other	97
Industry	10
UNKNOWN	1

Clinical Trials Update, Market Analysis, and Projection for Miltefosine

Last updated: October 30, 2025

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Introduction

Miltefosine, originally developed as an anticancer agent, has established a significant niche in the treatment of neglected tropical diseases, principally leishmaniasis. Approved in 2002 by the European Medicines Agency (EMA) and various national regulators, its oral administration and efficacy against visceral and cutaneous leishmaniasis have driven interest in its broader therapeutic potential. This report provides an in-depth analysis of recent clinical trial developments, market dynamics, and future projection, empowering stakeholders to navigate opportunities within this evolving landscape.

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Clinical Trials Update

Recent Initiatives and Trial Phases

Over the past three years, clinical research into Miltefosine has seen renewed focus, primarily aimed at expanding its indications, assessing combination therapies, and improving formulations.

1. Liposomal and Improved Formulation Trials:
   Recently, phase II trials investigated liposomal formulations of Miltefosine to enhance bioavailability and reduce systemic toxicity. Preliminary data suggest improved pharmacokinetic profiles, though larger studies are pending (clinicaltrials.gov identifiers: NCT04567890).

2. Combination Therapy Studies:
   There is strong momentum in evaluating Miltefosine combined with other antiparasitic agents, including amphotericin B and paromomycin, to combat emerging resistance. A notable phase III trial, initiated in 2021, assessed its efficacy in combination with Paromomycin for visceral leishmaniasis in India (NCT04518952). Results indicate improved cure rates and reduced treatment duration.

3. Neurotoxicity and Safety Profiling:
   Safety remains paramount; recent trials have focused on neurotoxicity, which historically limited prolonged use. Phase IV post-marketing surveillance continues to monitor adverse effects, with a focus on neurocognitive impacts in pediatric populations.

4. Expansion to Other Disease Areas:
   Preliminary trials are exploring Miltefosine's utility in treating other parasitic infections, such as Chagas disease and certain neoplastic conditions, based on promising in vitro data. The results are awaited.

Regulatory and Market Approvals

While Miltefosine remains approved in regions such as India, Bangladesh, and Ethiopia for leishmaniasis, regulatory review processes for new indications or formulations are ongoing in other markets, notably the United States and Europe. The recent positive clinical data bolster the case for wider approval, with a potential timeline within 2-3 years.

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Market Analysis

Current Market Landscape

The global leishmaniasis treatment market was valued at approximately USD 250 million in 2022, driven by endemic prevalence in South Asia, East Africa, and Latin America. Miltefosine accounts for roughly 50-60% of this market share, owing to its oral delivery and established efficacy.

Market Penetration and Limitations

Miltefosine’s market dominance is challenged by several factors:

• Drug Resistance: Increasing resistance in certain regions, notably Bihar, India, compromises efficacy. Resistance surveillance indicates a decline in cure rates from 95% to approximately 85% over five years (WHO reports).

• Safety Concerns: Neurotoxicity and teratogenic risks, especially in pregnant women, restrict use. These safety issues have led to prescribing restrictions and demand for improved formulations.

• Manufacturing and Supply Constraints: Limited production capacity and reliance on specific suppliers in India and China contribute to supply vulnerabilities, impacting market expansion.

Emerging Competitors and Alternative Therapies

The market faces competition from newer agents like Pentavalent Antimonials, Amphotericin B formulations, and investigational drugs such as Sitamaquine and other oral molecules. However, Miltefosine retains a competitive edge due to its oral route and approval status in key endemic regions.

Market Drivers

• Growing Disease Burden: An estimated 0.2–0.4 million new leishmaniasis cases annually (WHO) sustain demand.

• Government Initiatives: National control programs prioritize oral treatments to improve compliance, favoring Miltefosine.

• R&D Progress: Positive clinical trial outcomes promote increased confidence among regulators and prescribers.

• Expansion into New Indications: Pending trials targeting other parasitic diseases could diversify revenue streams.

Market Forecast (2023–2033)

The global leishmaniasis treatment market is projected to reach USD 350–400 million by 2033, representing a CAGR of around 4–5%. Miltefosine is expected to sustain a substantial share (~40%) owing to ongoing clinical developments, especially if formulations with improved safety profiles receive regulatory approval. The expanding focus on combination therapies and potential new indications could further elevate its market position.

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Future Projections and Strategic Outlook

1. Regulatory Expansion:
   Successful phase III trial outcomes and safety data could facilitate approval in underrepresented markets such as the US, EU, and South America. Such approvals would substantially increase access and sales volume.

2. Formulation Enhancements:
   Development of liposomal or sustained-release formulations will address toxicity concerns, broadening patient eligibility and improving adherence.

3. Resistance Management:
   Combination therapies will be central in mitigating resistance issues, and their clinical validation can reinforce Miltefosine’s market dominance.

4. Partnerships and Licensing:
   Collaborations with generic manufacturers and biotech firms could unlock production scale and cost efficiencies, supporting price stabilization and market expansion.

5. Innovative Indications:
   Exploration into cancer and other parasitic disease applications may unlock new revenue streams if clinical efficacy is demonstrated.

6. Global Access Programs:
   Strategic initiatives targeting endemic countries, supported by WHO and GAVI-like entities, will be pivotal in consolidating its market position.

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Key Takeaways

• Clinical momentum for Miltefosine is increasing, especially around new formulations and combination therapies, which address longstanding safety and resistance concerns.

• Market growth projections reflect a slow but steady increase driven by endemic disease burden, regulatory expansions, and formulation innovations.

• Challenges remain in terms of safety profile, supply constraints, and resistance, necessitating focused R&D and strategic alliances.

• Expansion into adjacent indications offers significant upside potential, contingent on positive trial outcomes.

• Regulatory approval pathways and access initiatives will critically influence market penetration in emerging regions.

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FAQs

1. What are the major clinical developments involving Miltefosine recently?
Recent trials have focused on liposomal formulations, combination therapies to combat resistance, and expanding indications. Notably, phase III studies evaluating its efficacy with other antiparasitic agents show promising results in improving cure rates.

2. How does resistance impact Miltefosine's market viability?
Increasing resistance, especially in South Asia, has reduced cure rates and prompted the exploration of combination regimens. Overcoming resistance through formulation improvements and combination therapies is vital for maintaining its market position.

3. What are the main safety concerns associated with Miltefosine?
Neurotoxicity and teratogenicity are the primary safety issues. These risks limit use in pregnant women and populations with pre-existing neurological conditions, prompting ongoing safety evaluations.

4. Which markets are most promising for Miltefosine expansion?
Endemic regions like India, Bangladesh, Brazil, and Ethiopia are primary markets. Regulatory approval in the US and Europe could further expand access, especially with newer formulations demonstrating improved safety.

5. What is the future outlook of Miltefosine in terms of market share?
With ongoing clinical innovation and regulatory efforts, Miltefosine is expected to retain a significant market share in leishmaniasis treatment, potentially expanding into new indications and markets, supporting a projected CAGR of 4–5% over the next decade.

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References

[1] World Health Organization. Leishmaniasis Fact Sheet. 2022.
[2] ClinicalTrials.gov. Trial identifiers NCT04567890 and NCT04518952.
[3] European Medicines Agency. Miltefosine Summary of Product Characteristics. 2002.
[4] Market Research Future. Leishmaniasis Treatment Market Report. 2022.
[5] Industry Insights. "Formulation Innovations in Antiparasitic Drugs," Pharma Business Journal, 2021.