On November 16, 2018, the first treatment for sleeping sickness that relies on pills alone was approved by European Medicines Agency, Europe’s drug regulatory agency. This disease which can result in madness and eventually death if not treated has for many years been neglected and patients had to undergo a complex and sometimes dangerous intravenous regimen requiring hospitalization just to treat the disease.
This tropical disease transmitted by tsetse flies infected with the human African Trypanosomiasis, a parasite that digs into the brain when transmitted to human as a neglected tropical disease (NTDs) and has been the research focus of Victor Kande Betu Kumeso, a local Congolese physician under the umbrella of Drug for Neglected Diseases Initiative (DNDi).
Until a decade ago, the drug Melarsoprol (discovered in the 1940s and sometimes better known under its brand name Arsobal) was used for the intravenous treatment but the use was later discouraged because it contains an arsenic derivative that corroded veins, triggered convulsions and killed 5 per cent of the patients who got it.
In the early 2000s, the Médecins Sans Frontières/Doctors without Borders (MSF) which had been on the frontline of sleeping sickness outbreaks in the 1990s called for the creation of DNDi. They discovered the intravenous drug, eflornithine, which must be given over many days with intravenous fluids is a big burden in the supply chain for rural hospitals because it weighs about 56.7 kg or 125 pounds. Eflornithine drug regimen is also extremely complex. The therapy is an extensive 56 intravenous infusions (4-times per day across 14 days) and the attention of medical professionals and an extended hospital stay are necessary requirements.
In 2009, the DNDi and its partners launched the first new HAT treatment in 25 years – nifurtimox. Nifurtimox is often used in a combination treatment with eflornithine, which simplifies the regimen of eflornithine alone by introducing this oral compound. Though reducing the earlier treatment time of eflornithine alone by half, this regimen still requires a hospital stay and trained healthcare professionals in order to be administered.
Kande who investigates the epidemiology of sleeping sickness, the efficacy and safety of several drugs for the treatment the disease, and has treated thousands of sleeping sickness patients throughout his long career– from his time as a local doctor in the remote Equateur region of the Democratic Republic of Congo (DRC) – up until his tenure as head of the DRC’s National Sleeping Sickness Programme is one of the first to report of the resurgence of sleeping sickness in 2001, calling for more aid, inter-country collaboration and improved healthcare facilities and treatment options have dreamed for decades for the discovery of a simple all-oral drug for the disease.
“Those affected by sleeping sickness are some of the most vulnerable and live in some of the most remote areas of the Congo, if not the world. They need a treatment that is safe, effective and simple. An all-oral treatment has been a dream of mine for decades. Fexinidazole is a huge leap in how we can tackle this deadly disease.” – Dr Victor Kande
Under DNDi, Kande investigated Acoziborole (SCYX-7158) and Fexinidazole as anti-parasitic oral medicines for sleeping sickness. In 2009 Acoziborole was selected as a promising candidate following years of compound optimization and Sanofi which held the patent to the fexinidazole was asked to reformulate it for sleeping sickness. Fexinidazole is drug created in the 1980s by Hoechst, a German drug company, but was later abandoned.
Kande led this $63 million investigation funded by seven European countries, the Bill and Melinda Gates Foundation, Doctors Without Borders and other donors. As the principal investigator of the DNDi’s clinical trials, he supervised the screening of 2 million villagers and the trails on over 740 patients in 10 sites in the DRC and the Central African Republic.
The finds of the trail using fexinidazole as an all-oral drug for treating sleeping sickness which was published in The Lancet on November 04, 2017 showed that oral fexinidazole is effective and safe for the treatment of the most common strain of sleeping sickness, Trypanosoma brucei gambiense (g-HAT), compared with nifurtimox-eflornithine combination therapy in late-stage HAT patients and that Fexinidazole could be a key asset in the elimination of this fatal neglected disease. The new drug, fexinidazole, cures the disease within 10 days and had been recommended by EMA for the treatment of sleeping sickness.
Considering the difficulty of achieving such a feat in an area where there are few enough passable roads, let alone hospitals with the right drugs and patients who can afford them, Richard Lehman, the British primary care physician and academic and senior research fellow at the department of primary health care at the University of Oxford described Kande as a ‘true hero of medicine’ in his a weekly review of journals, on the website of the British Medical Journal. “Work of this kind is beyond admirable”, he wrote. In 2018 Kande was awarded the Anne Maurer Cecchini award of the Geneva Health Forum.
With treatment of sleeping sickness radically simplified, the disease could become a candidate for elimination as there are usually fewer than 2,000 cases in the world each year.