Fexinidazole is a

medication A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and re ...

used to treat

African trypanosomiasis African trypanosomiasis, also known as African sleeping sickness or simply sleeping sickness, is an insect-borne parasitic infection of humans and other animals. It is caused by the species ''Trypanosoma brucei''. Humans are infected by two typ ...

(sleeping sickness) caused by ''

Trypanosoma brucei gambiense ''Trypanosoma brucei'' is a species of parasitic kinetoplastid belonging to the genus ''Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclusively extracellu ...

''. It is effective against both first and second stage disease. Some evidence also supports its use in

Chagas disease Chagas disease, also known as American trypanosomiasis, is a tropical parasitic disease caused by ''Trypanosoma cruzi''. It is spread mostly by insects in the subfamily ''Triatominae'', known as "kissing bugs". The symptoms change over the cou ...

. It is taken by mouth. Common side effects include nausea, vomiting, headache, and trouble sleeping. Other side effects may include

QT prolongation Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, ...

psychosis Psychosis is a condition of the mind that results in difficulties determining what is real and what is not real. Symptoms may include delusions and hallucinations, among other features. Additional symptoms are incoherent speech and behavior ...

, and

low white blood cells Leukopenia () is a decrease in the number of leukocytes (WBC). Found in the blood, they are the white blood cells, and are the body's primary defense against an infection. Thus the condition of leukopenia places individuals at increased risk of inf ...

. It is unclear if use during

pregnancy Pregnancy is the time during which one or more offspring develops ( gestates) inside a woman's uterus (womb). A multiple pregnancy involves more than one offspring, such as with twins. Pregnancy usually occurs by sexual intercourse, but ca ...

breast feeding Breastfeeding, or nursing, is the process by which human breast milk is fed to a child. Breast milk may be from the breast, or may be expressed by hand or pumped and fed to the infant. The World Health Organization (WHO) recommends that brea ...

is safe. Fexinidazole is in the

antiparasitic Antiparasitics are a class of medications which are indicated for the treatment of parasitic diseases, such as those caused by helminths, amoeba, ectoparasites, parasitic fungi, and protozoa, among others. Antiparasitics target the parasitic agent ...

and the

nitroimidazole 5-Nitroimidazole is an organic compound with the formula O2NC3H2N2H. The nitro group at position 5 on the imidazole ring is the most common positional isomer. The term nitroimidazole also refers to a class of antibiotics that share similar chemi ...

family of medications. It is believed to work by turning on certain enzymes within the parasites that result in their death. Fexinidazole was first described in 1978. It was given a positive opinion by the

European Medicines Agency The European Medicines Agency (EMA) is an agency of the European Union (EU) in charge of the evaluation and supervision of medicinal products. Prior to 2004, it was known as the European Agency for the Evaluation of Medicinal Products or Euro ...

in 2018. It is on the

World Health Organization's List of Essential Medicines The WHO Model List of Essential Medicines (aka Essential Medicines List or EML), published by the World Health Organization (WHO), contains the medications considered to be most effective and safe to meet the most important needs in a health ...

. Development for sleeping sickness was funded by the

Drugs for Neglected Diseases initiative The Drugs for Neglected Diseases ''initiative'' (DND''i'') is a collaborative, patients' needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected tropical diseases, neglected diseas ...

in collaboration with

Sanofi Sanofi S.A. is a French multinational pharmaceutical and healthcare company headquartered in Paris, France. Originally, the corporation was established in 1973 and merged with Synthélabo in 1999 to form Sanofi-Synthélabo. In 2004, Sanofi-Syn ...

. Fexinidazole was approved for medical use in the United States in July 2021.

Medical use

Sleeping sickness

A trial in Africa found fexinidazole to be 91% effective at treating sleeping sickness. Though less effective than

nifurtimox Nifurtimox, sold under the brand name Lampit, is a medication used to treat Chagas disease and sleeping sickness. For sleeping sickness it is used together with eflornithine in nifurtimox-eflornithine combination treatment. In Chagas disease it ...

with

eflornithine Eflornithine, sold under the brand name Vaniqa among others, is a medication used to treat African trypanosomiasis (sleeping sickness) and excessive hair growth on the face in women. Specifically it is used for the 2nd stage of sleeping sickness ...

in severe disease, fexinidazole has the benefit that it can be taken by mouth. Fexinidazole is the first drug candidate for the treatment of advanced-stage sleeping sickness in thirty years.

Other

It has activity against ''

Trypanosoma cruzi ''Trypanosoma cruzi'' is a species of parasitic euglenoids. Among the protozoa, the trypanosomes characteristically bore tissue in another organism and feed on blood (primarily) and also lymph. This behaviour causes disease or the likelihood of ...

'', ''

Tritrichomonas foetus ''Tritrichomonas foetus'' is a species of single-celled flagellated parasites that is known to be a pathogen of the bovine reproductive tract as well as the intestinal tract of cats. In cattle, the organism is transmitted to the female vagina ...

'', ''

Trichomonas vaginalis ''Trichomonas vaginalis'' is an anaerobic, flagellated protozoan parasite and the causative agent of a sexually transmitted disease called trichomoniasis. It is the most common pathogenic protozoan that infects humans in industrialized countries ...

'', ''

Entamoeba histolytica ''Entamoeba histolytica'' is an anaerobic parasitic amoebozoan, part of the genus ''Entamoeba''. Predominantly infecting humans and other primates causing amoebiasis, ''E. histolytica'' is estimated to infect about 35-50 million people worldwid ...

'', and ''

Trypanosoma brucei ''Trypanosoma brucei'' is a species of parasitic Kinetoplastida, kinetoplastid belonging to the genus ''Trypanosoma'' that is present in sub-Saharan Africa. Unlike other protozoan parasites that normally infect blood and tissue cells, it is exclus ...

''. It has not been found to be useful for

visceral leishmaniasis Visceral leishmaniasis (VL), also known as kala-azar (Hindi: kālā āzār, "black sickness") or "black fever", is the most severe form of leishmaniasis and, without proper diagnosis and treatment, is associated with high fatality. Leishmaniasis ...

Mechanism of action

The biologically relevant active metabolites in vivo are the sulfoxide and sulfone.

History

Fexinidazole was discovered by the German pharmaceutical company

Hoechst AG Hoechst AG () was a German chemicals then life-sciences company that became Aventis Deutschland after its merger with France's Rhône-Poulenc S.A. in 1999. With the new company's 2004 merger with Sanofi-Synthélabo, it became a subsidiary of the ...

, but its development as a pharmaceutical was halted in the 1980s.

Society and culture

Fexinidazole Winthrop, a

-Aventis product developed with the

Drugs for Neglected Diseases Initiative The Drugs for Neglected Diseases ''initiative'' (DND''i'') is a collaborative, patients' needs-driven, non-profit drug research and development (R&D) organization that is developing new treatments for neglected tropical diseases, neglected diseas ...

(DNDi), received a positive endorsement from the

in 2018, for use in non-European markets. It was approved for the treatment of ''Trypanosoma brucei gambiense'' human African trypanosomiasis (HAT) in the Democratic Republic of the Congo (DRC) in December 2018. Fexinidazole was included in the 'role of honour' in Préscrire magazine's 2020 prize lis
Fexinidazole Winthrop° (fexinidazole) : au Tableau d'Honneur 2020

Veterinary use

Fexinidazole is promising in African animal trypanosomiasis. Torreele et al. 2010 found the drug to be effective against ''T. b. gambiense'' infection of

mice A mouse ( : mice) is a small rodent. Characteristically, mice are known to have a pointed snout, small rounded ears, a body-length scaly tail, and a high breeding rate. The best known mouse species is the common house mouse (''Mus musculus' ...

rats Rats are various medium-sized, long-tailed rodents. Species of rats are found throughout the order Rodentia, but stereotypical rats are found in the genus ''Rattus''. Other rat genera include ''Neotoma'' (pack rats), ''Bandicota'' (bandicoot ...

rabbits Rabbits, also known as bunnies or bunny rabbits, are small mammals in the family Leporidae (which also contains the hares) of the order Lagomorpha (which also contains the pikas). ''Oryctolagus cuniculus'' includes the European rabbit specie ...

and

beagles The beagle is a breed of small scent hound, similar in appearance to the much larger foxhound. The beagle was developed primarily for hunting hare, known as beagling. Possessing a great sense of smell and superior tracking instincts, the b ...

. They also found no toxicity in any of them, including a lack of

mutagenicity In genetics, a mutagen is a physical or chemical agent that permanently changes genetic material, usually DNA, in an organism and thus increases the frequency of mutations above the natural background level. As many mutations can cause cancer in ...

despite

in vitro ''In vitro'' (meaning in glass, or ''in the glass'') studies are performed with microorganisms, cells, or biological molecules outside their normal biological context. Colloquially called "test-tube experiments", these studies in biology an ...

mutagenicity.

References

External links

* {{Portal bar , Medicine Antiparasitic agents German inventions Nitroimidazoles Phenol ethers Thioethers World Health Organization essential medicines Wikipedia medicine articles ready to translate