Investigational new drugs for the treatment of leishmaniasis

Expert Opin Investig Drugs. 2024 Oct;33(10):1029-1046. doi: 10.1080/13543784.2024.2400139. Epub 2024 Sep 10.

Abstract

Introduction: Over the past 20 years, significant progress has been made in anti-leishmanial therapy. Three new drugs/formulations are available for the treatment of various forms of leishmaniasis, namely oral miltefosine, paromomycin and liposomal amphotericin B. However, these advances in drug development have added considerable complexity for clinicians including toxicity, emergence of resistance and decreased sensitivity of available drugs. The development of newer drugs with less toxicity and more efficacy is urgently needed.

Areas covered: This review comprehensively examines the latest developments and current status of antileishmanial drugs for the treatment of leishmaniasis across the world. Several new investigational drugs that showed anti-leishmanial activity under in vitro or in vivo conditions and either underwent the phase-I/II clinical trials or are on the verge of entering the trials were reviewed. We also delve into the challenges of drug resistance and discuss the emergence of new and effective antileishmanial compounds.

Expert opinion: The available treatments for leishmaniasis are limited in number, toxic, expensive, and demand extensive healthcare resources. Every available antileishmanial drug is associated with several disadvantages, such as drug resistance and toxicity or high cost. Miltefosine is potentially teratogenic. New antileishmanial drugs/treatment modalities are sorely needed for expanding future treatment options.

Keywords: Anti-leishmanial drugs; drug treatment; investigational drugs; leishmaniasis; plant-based investigational drug.

Publication types

  • Review

MeSH terms

  • Amphotericin B / administration & dosage
  • Amphotericin B / adverse effects
  • Amphotericin B / pharmacology
  • Animals
  • Antiprotozoal Agents* / administration & dosage
  • Antiprotozoal Agents* / adverse effects
  • Antiprotozoal Agents* / pharmacology
  • Drug Design
  • Drug Development*
  • Drug Resistance*
  • Drugs, Investigational* / administration & dosage
  • Drugs, Investigational* / pharmacology
  • Humans
  • Leishmaniasis* / drug therapy
  • Phosphorylcholine / administration & dosage
  • Phosphorylcholine / analogs & derivatives
  • Phosphorylcholine / pharmacology
  • Phosphorylcholine / therapeutic use

Substances

  • Drugs, Investigational
  • Antiprotozoal Agents
  • miltefosine
  • Amphotericin B
  • Phosphorylcholine