Eliminating sleeping sickness has never been closer

Treating Neglected Tropical Diseases, a Core Pillar of Foundation S

The World Health Organization has identified 20 neglected tropical diseases (NTDs). Mainly in tropical areas, they affect more than one billion people, often in very vulnerable communities. They are called neglected because few resources are currently dedicated to them. However, they continue to have a significant impact on the lives of the people concerned. Indeed, it is estimated that the cost of mortality due to NTDs in Africa alone is more than $5 billion per year.

The World Health Organization has identified

20
neglected tropical diseases (NTDs)

More than

1 BN
people affected

More than

$5 BN
per year it is the estimated cost of mortality due to NTDs in Africa

"These diseases have a profound effect on people's lives: they prevent adults from working, children from going to school. They affect the poorest populations and have a lasting health, social and economic impact on patients, including disabilities, disabling scars and stigmatization", explains Philippe Neau, Head of the Neglected Tropical Diseases division at Foundation S.

Sanofi's commitment to these diseases is not new. "Everything we do at Sanofi in the field is mainly philanthropic: we develop and donate all the molecules that treat sleeping sickness and have done so for more than two decades," says Philippe Neau. "We established a partnership with WHO back in 2001: in the $5 million we donate every year, there is of course the donation of products for sleeping sickness but there is also the part for other NTDs like Chagas disease, leishmaniasis or yaws for which WHO conducts information and education activities."

An expert and passionate team

Philippe Neau has been working at Sanofi for more than 25 years in the development of new drugs, in particular new molecules for treatment or prevention for developing countries. He has been involved for the past 5 years in the development of a new compound, fexinidazole, the first fully oral, treatment for sleeping sickness. Sanofi currently provides 4/5ths of the treatments for sleeping sickness and has chosen, in line with the WHO's roadmap, to make the elimination of this disease by 2030 one of its main objectives.

"I have always been oriented towards improving treatment access to patients, i.e., not just doing research, but also ensuring that the molecules ultimately reach the patient. This seems essential to me," explains Philippe. Neau.

In addition to the WHO, Foundation S works with strategic partners such as Médecins Sans Frontières for the delivery of the medicines and NGOs such as DNDi (Drugs for Neglected Diseases Initiative), with whom the company has worked for 14 years.

"DNDi brings its development expertise while Sanofi brings its expertise in registering new compounds. We develop everything that needs to be developed to prove the efficacy, safety and security of the product so that we can obtain approval from the health authorities to distribute the medicines through WHO to patients."

Philippe Neau, Head of the Neglected Tropical Diseases division at Foundation S.

Sleeping sickness, a deadly plague

Transmitted by the bite of the tsetse fly, the parasite that causes sleeping sickness takes two forms: trypanosoma brucei gambiense, which is present in the west-central part of Africa (much of the Democratic Republic of Congo) and accounts for 90 to 95 percent of cases. Trypanosoma brucei rhodesiense is found in the east-central part of Africa (Malawi, Uganda, Zambia and Tanzania). In both cases, without treatment, the disease is fatal within two years. Indeed, the first stage of the infection lasts for 18 months with headaches, itching and anemia. In the second stage, the parasite crosses the blood-brain barrier, and the symptoms worsen: sleep disorders and neuropsychiatric disorders.

"The evolution of the disease means that, in the end, people have psychotic episodes. It's an extremely scary disease," says Philippe Neau. However, great progress towards its elimination has already been made. "We've gone from about 30,000 cases in 2001 and over time we've been able to reduce, the number of diagnosed cases of sleeping sickness drastically. By 2021, there were about 800 cases. This is a work done with all the partners in the countries under the WHO umbrella. Most of the diagnosed patients are living among the most remote areas of Africa, sometimes war zones, where access is extremely difficult."

A close elimination, thanks to innovation and cooperation

The decline in the number of diagnosed cases is due to major developments in the treatment of the disease. The first drug used for sleeping sickness, is arsenic-based with known safety profile. Since then, pentamidine has been used for less severe cases and a combined treatment composed of Nifurtimox and eflornithine has been developed. It is 95% effective but is only given as an injection, in hospital, for at least ten days. "And it's a treatment that can weigh more than 10Kg to transport deep into the bush. Until 2020, there were no other treatment options," says Philippe Neau.

The first oral treatment for sleeping sickness

A first significant advancement in treatment evolution was launched with the arrival of fexinidazole, registered in December 2018 in the Democratic Republic of Congo. It is the first approved all-oral treatment for sleeping sickness and the first oral treatment jointly developed for sleeping sickness by Sanofi and DNDi. "It's only 10 days of tablets. It completely revolutionizes the paradigm: patients are much less afraid; they can also take the treatment without spending 10 days or more in the hospital. During that time, they were not in the fields, they were not taking care of their families... So, patients were afraid of being diagnosed positive. Now it's much easier," Philippe Neau says.
"Until recently, before fexinidazole, you had to do a lumbar puncture routinely to assess how severe the disease was. So, there was also the fear of undergoing this lumbar puncture, you had to have the courage of the diagnosis."

A new molecule tested in clinical trials

A major step towards elimination is emerging with a new molecule, acoziborole. "It would consist of 3 tablets to be taken at once. Under these conditions, we observe between 95 and 98% efficacy and has a favourable safety profile, with no significant drug-related safety signals reportedin the clinical study conducted by DNDi on approximately 200 patients and published last November in The Lancet Infectious Diseases medical journal¹. These pivotal results will support another important milestone in the quest. Upon the EMA’s positive opinion and local approval, Sanofi will donate acoziborole to the WHO through its philanthropic organization, Foundation S."

Rhodesian complicates total eradication of sleeping sickness

There are other elements at play to ensure elimination of the disease. The frequency of testing and diagnosis must not be reduced because the disease vector, the tsetse fly, is not going to disappear, even though there are programs to reduce its population, including the use of nets to attract and capture the fly. The rhodesiense form, on the other hand, is present in wildlife as well, making total eradication of the disease impossible.

The work of Foundation S and DNDi on this less common form suggests great progress. Until now, this form could only be treated with melarsoprol. A clinical study in patients with rhodesiense has been conducted to demonstrate the efficacy and safety of fexinidazole in these patients. Once approved by health authorities it would be a revolution for these patients to have a treatment by pill.

The elimination goal is within reach but relies on joint efforts by Foundation S and its longtime partners. "Only a collaborative approach can work: eliminating a disease is a real challenge, we are aware of that, but if we succeed, it will be the first time that we eliminate a deadly disease without a vaccine!" concludes Philippe Neau.