Phase III clinical trial with Bayer’s Nifurtimox demonstrates safety and efficacy of new formulation to treat children with Chagas disease
- Category: Small Molecules
- Published on Thursday, 14 March 2019 17:59
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Largest clinical treatment study to date in pediatric patients with Chagas disease / Easily dividable and dispersible nifurtimox tablet for improved weight-adjusted dosing of newborns, infants, and children
BERLIN, Germany / BARCELONA, Spain I March 14, 2019 I Bayer today presented the results of the CHICO (CHagas disease In Children treated with NifurtimOx) phase III clinical study of nifurtimox in pediatric patients with Chagas disease at the “XV. Taller sobre la enfermedad de Chagas” conference in Barcelona.
CHICO was a prospective, randomized, double-blind, historically controlled phase III trial to evaluate the efficacy, safety, and pharmacokinetics of nifurtimox in 330 pediatric patients with acute or chronic Chagas disease conducted at 25 investigational sites in Argentina, Bolivia, and Colombia between 2016 and 2018.
The study met its primary endpoint by demonstrating the superiority of the 60-day nifurtimox treatment compared with historical placebo control in serological response at one year after end of treatment. In the overall study population, the serological response to a shorter nifurtimox treatment duration of 30 days was lower when compared to the 60-day treatment. Treatment with nifurtimox at body weight-adjusted dosing showed a good safety profile.
“An adequate dispersable formulation of nifurtimox is a big step forward toward achieving the goal of treating all infected children,” said Dr Jaime Altcheh, Head of the Department of Parasitology and Chagas disease at the Ricardo Gutierrez Children’s Hospital in Buenos Aires, Argentina, and Coordinating Investigator of the phase III CHICO trial. “Early treatment after infection is very important to prevent manifestation of the disease in adulthood.”
The targets for controlling Chagas disease are eliminating transmission, controlling the vector, treating girls and women at childbearing age (to avoid transplacental transmission), and testing blood prior to transfusion. In addition, the aim is to make healthcare access available for the infected population at all stages of the disease
The treatment of Chagas disease is based on only two nitroheterocyclic compounds, nifurtimox and benznidazole. To date, nifurtimox has only been available as a 120 mg tablet, which is difficult to administer, especially to younger children. Bayer has now developed a 30 mg tablet. Both tablets are now fast dispersible formulations, which can be easily divided. They can also be rapidly dissolved in water to form a slurry, which can be given to those with difficulties in swallowing tablets. The new formulations were successfully used in CHICO and will improve dosing accuracy, safety, and adherence to treatment in children of all age groups.
“Children are the most vulnerable patient group suffering from Chagas disease. With the successful completion of the CHICO study, an important milestone of our long-standing commitment to improve the treatment of Chagas has been achieved,” said Dr Joerg Moeller, Member of the Executive Committee of Bayer AG´s Pharmaceutical Division and Head of Research and Development.
The majority of infections are asymptomatic. Symptomatic cases only show minor, flu-like symptoms which appear directly after infection. About two months later, Chagas disease enters a chronic stage that progresses for years, leading to severe organ damage and finally to sudden cardiac death. Education, early diagnosis, and treatment are essential in the fight against Chagas disease
Today fewer than 1% of people infected with Chagas disease are treated due to low disease awareness and limited access to treatment. Bayer is committed to improving access to nifurtimox by new applications for registrations and making the new formulations available in countries with a high disease burden.
About Chagas disease
Chagas disease is named after Carlos Ribeiro Justiniano Chagas, a Brazilian physician and researcher who discovered the disease in 1909. Chagas is an infectious disease caused by single-cell parasites (trypanosoma) which are transmitted to humans via the feces of kissing bugs or triatomines. Chagas disease can also be transmitted by infected blood transfusions, organ transplantation, or during pregnancy or birth from the infected mother to her unborn child.
Infected patients are mainly present in the endemic countries of Latin America. However, transmission of Chagas disease in non-endemic countries – that is, transmission in countries outside Latin America with exceptional or no vectorial transmission – has emerged since the beginning of the year 2000, linked to local and transnational population movements and notably migration.
One third of people affected develop chronic heart diseases. Others suffer from an abnormal enlargement of the digestive organs or even neurological or mixed alterations. Many die as a result of sudden cardiac arrest or heart failur
The disease has already been recognized as a global problem: the world’s population movements (i.e. mainly migration) have carried the parasite abroad, mainly to North America and Europe. There it can be transmitted either congenitally, to the offspring of infected mothers, or horizontally via blood or organ donations. In Spain, the European country with the highest prevalence of Chagas disease, the estimated number of patients is 48,000 to 96,000 cases.
Bayer and Chagas disease
Although one quarter of the Latin American population is at risk of contracting the disease, Chagas is still called a “forgotten disease”, but even more it is a “silent disease” as it had remained “hidden” for years or even decades due to lack of specific symptoms.
For a long time there were no means of treating Chagas disease effectively. It was only in the 1960s that large-scale studies with nifurtimox proved its efficacy. The compound, discovered by Bayer in Wuppertal, Germany, was first introduced under the brand name Lampit® in Argentina in 1970, and shortly afterwards in other South American countries.
The recommended treatment with Lampit® currently takes between about 60 to 90 days and should not exceed 120 days using the 120 mg tablet formulation. Lampit® is on the WHO’s lists of “Essential Medicines” for both adults and children.
In 2002 the World Health Organization (WHO) and Bayer combined their strengths in the fight against Chagas disease. Since then, Bayer has been providing WHO with Lampit® free of charge, combined with financial resources for logistics and distribution. More recently Bayer has also contributed toward disease awareness programs, education and training as well as surveillance activities.
As the originator of nifurtimox and as a signatory of the ”London Declaration on NTDs” of 2012, Bayer takes responsibility for making the drug available for as long as it takes to eliminate Chagas disease.
The fight against Chagas disease poses a special challenge, as it has turned from an endemic disease in Latin America to a global public health threat. The control of the disease by screening programs, access to treatment and vector control are important measures on the path of eliminating the disease by 2030.
A prerequisite to achieve this goal is that all stakeholders in an aligned approach step up their efforts and contributions. This was concluded by all partners at the first Chagas Stakeholder Meetings with PAHO (Pan American Health Organization) and WHO in 2018.
Bayer is a dedicated partner in this network. The decision to joining the Global Chagas Coalition in 2018 was a clear endorsement of the company’s special emphasis to fight Chagas disease.
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to www.bayer.com.