Discovery, Development, Inventions and Patent Review of Fexinidazole: The First All-Oral Therapy for Human African Trypanosomiasis

Abstract

Human African trypanosomiasis (HAT or ‘sleeping sickness’) is a neglected tropical disease. If untreated, it is always fatal and leads to death. A few treatments are available for HAT, but most of them require a skilled professional, which increases the financial burden on the patient. Recently, fexinidazole (FEX) has been approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of stage-1 (hemolymphatic) as well as stage-2 (meningoencephalitic) of HAT. Before the FEX approval, there were separate treatments for stage-1 and stage-2 of HAT. This study reviews the discovery, development timeline, inventions, and patent literature of FEX. It was first approved by EMA and USFDA in 2018 and 2021, respectively. FEX was also added to the World Health Organization’s list of essential drugs in 2019. The patent literature search revealed many types of patents/patent applications (compound, salt, process, method of treatment, drug combinations, and compositions) related to FEX, which have been summarized in this article. The authors foresee a great scope to develop more inventions based on FEX (novel salts, polymorphs, drug conjugates, cyclodextrin complex, etc.) for the treatment of many protozoal diseases (Leishmaniasis and Chagas disease), inflammatory diseases, and other microbial infections. New combinations of FEX with other treatments of HAT may also provide fruitful results. This review might be useful to the scientists working on the HAT and other neglected diseases to develop novel inventions and innovations of therapeutic relevance.

Selenium and COVID-19: A spotlight on the clinical trials, inventive compositions, and patent literature

“…The patent literature search was performed on Sci-Finder, Espacenet, Patentscope, and USPTO databases on June 27, 2022 [51] , [52] , [53] , [54] , [55] . The keywords “selenium + COVID-19” and “selenium + SARS-CoV-2” were selected for patent searching on different patent databases (Espacenet, USPTO, Scifinder, and Patentscope).…”

Fexinidazole for Human African Trypanosomiasis, the Fruit of a Successful Public-Private Partnership

“…Fexinidazole (Hoe 239) is a 2-substituted 5-nitroimidazole ( Figure 4 ) that had been in preclinical development by Hoechst [ 30 , 31 ]. The original patents for fexinidazole (US4042705A and CA1079738A) have expired [ 32 ]. However, there is an active patent (US9585871B2) for the use of fexinidazole for leishmaniasis in dogs [ 32 ], now held by Boehringer Ingelheim Animal Health after their acquisition of Merial.…”

“…The original patents for fexinidazole (US4042705A and CA1079738A) have expired [ 32 ]. However, there is an active patent (US9585871B2) for the use of fexinidazole for leishmaniasis in dogs [ 32 ], now held by Boehringer Ingelheim Animal Health after their acquisition of Merial.…”

Plant Terpenoids as Hit Compounds against Trypanosomiasis

“…For the first phase, suramin (Naganinum ® , Naganol ® ) and pentamidine (Nebupent ® , Pentam ® ) are the first line drugs. For the final stage of sleeping sickness, the treatment includes the use of melarsoprol (Arsobal ® ), eflornithine (Vaniqa ® ) and the nifurtimox (Lampit ® ) -eflornithine combination therapy (NECT) [ 39 ]. Recently, fexinidazole was approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of phase-1 and phase-2 HAT [ 39 ].…”

“…For the final stage of sleeping sickness, the treatment includes the use of melarsoprol (Arsobal ® ), eflornithine (Vaniqa ® ) and the nifurtimox (Lampit ® ) -eflornithine combination therapy (NECT) [ 39 ]. Recently, fexinidazole was approved by the European Medicine Agency (EMA) and the United States Food and Drug Administration (USFDA) as the first all-oral therapy for the treatment of phase-1 and phase-2 HAT [ 39 ]. Additionally, acoziborole a recently developed benzoxaborole, is currently in advanced clinical trials, for treatment of phase-1 and phase-2 caused by both T.b.…”