Bitten by the ‘kissing bug’

GENEVA, Switzerland—Eisai Co. Ltd. and the Drugs forNeglected Diseases initiative (DNDi) have signed a collaboration and licenseagreement for the clinical development of a promising new drug for thetreatment of Chagas disease, a fatal infectious disease that is endemic in 21Latin American countries, where it causes about 14,000 deaths per year.

In addition, according to World Health Organization (WHO),the number of diagnosed cases has been increasing over recent years due topopulation mobility, which has shifted transmission to areas classified asnonendemic, such as Australia, Canada, Europe, Japan and the United States.This increase presents additional risks of transmission through bloodtransfusion, congenital infection and organ transplantation.

Chagas disease is transmitted by the bite of the "kissing bug,"or vinchuca. About 8 million people are believed to carry it, and about a thirdof these—if left untreated—will develop serious heart or intestinal damage thatcould lead to death. Without an adequate diagnosis and treatment, one in everythree to four Chagas disease patients develops a potentially fatal form of thedisease, which involves the enlargement of the heart. Often, patients willrequire a pacemaker, implantable defibrillators, and in some cases, need toundergo a heart transplant.

Many patients, however, die suddenly, some withoutever realizing that they had been infected. Development of a new treatment thatcould be effective for the chronic phase of the disease, particularly inadults, would represent a breakthrough.

Dr. Isabela Ribeiro, senior R&D project manager withDNDi, notes that Eisai developed

ravuconazole several years ago as an anti-fungal drugtreatment and discovered that it showed potent activity both in vitro and in vivo against the pathogen responsible for Chagas disease. DNDi did the Phase1 evaluation, while Eisai continued development of the drug.

So the "time wasright," according to Ribeiro, to formalize her organization's ties with Eisai.

Under the terms of the agreement, DNDi retains soleresponsibility for the clinical development to assess the safety and efficacyof E1224, which is a pro-drug of ravuconazole, in patients with Chagas diseasewithin endemic countries.

Eisai will provide DNDi with its scientific expertisein clinical development as well as supply the drug for the clinical studies.Eisai will also have the option to become the industrial partner with DNDi tomanufacture, register and make available E1224 at an affordable price to thepublic sector in endemic countries.

As a pro-drug, explains Eisai president and CEO Haruo Naito,E1224 exhibits almost no activity when administered to humans or animals, butis rapidly metabolized into an active form and exerts the same effects asravuconazole.

"We are extremely pleased to establish an innovative andcollaborative product development partnership with DNDi to address jointly theunmet needs of patients suffering from neglected diseases," says Naito, "Inrecognition of the plight of millions of Chagas patients, Eisai is steppingforward to join the quest for bringing a new, effective and affordabletreatment option to them."

With Phase 1 studies completed, DNDi is reviewing itsdocumentation to determine if any bridging evaluation needs to be done prior tobeginning clinical trials next year, Ribeiro says. If the drug is brought tomarket, her organization and Eisai will work together to determine distributionand pricing, which are often very important components of public sectorinvolvement, she notes.

"We are devising an action plan for sustainable distributionand affordable pricing for counties where the disease is endemic," Ribeiroadds.

A two-tiered pricing strategy is likely, with the drug soldat cost in Latin America and at a yet-to-be established, but higher price innon-endemic countries, which Eisai will handle.

DNDi is a not-for-profit partnership working to research anddevelop new and improved treatments for Chagas disease as well as otherneglected diseases such as malaria, leishmaniasis and human Africantrypanosomiasis. The organization was established in 2003 by the Oswaldo CruzFoundation from Brazil, the Indian Council for Medical Research, the KenyaMedical Research Institute, the Ministry of Health of Malaysia, the PasteurInstitute and Médecins sans Frontières (MSF). WHO/TDR acts as a permanentobserver. Since 2007, DNDi has delivered three products: fixed-doseantimalarials "ASAQ" and "ASMQ," and a treatment for the advanced stage ofsleeping sickness NECT (nifurtimox-eflornithine combination therapy).