The University has received a $22.6 million grant from the Bill & Melinda Gates Foundation to support a pivotal clinical trial of a promising new oral drug for treating African sleeping sickness.
African sleeping sickness, or trypanosomiasis, is a deadly parasitic disease transmitted by tsetse flies. More than 300,000 people in sub-Saharan Africa are infected with the disease, and an estimated 60 million people are at risk.
The Gates foundation grant will enable an international research consortium led by UNC faculty to complete a phase III clinical trial of the drug DB289, known generically as pafuramidine maleate, in the Democratic Republic of Congo, Sudan and Angola. This trial is the final step required before seeking approval of the drug from the U.S. Food and Drug Administration.
“This new Gates foundation grant will fund the final stages of development and commercialization of what could be the first new drug for sleeping sickness in 50 years, and a major advance over current treatments,” said Dr. Richard R. Tidwell, a professor in UNC’s schools of medicine and pharmacy and the principal investigator for the project.
Drugs currently used to treat sleeping sickness require painful injections and are highly toxic. Pafuramidine is far less toxic and, because it is given orally, is much better suited for use in the remote areas of rural Africa, where sleeping sickness is typically found.
Besides conducting the phase III clinical trial, the consortium will study pafuramidine in children between the ages of 6 and 12, begin developing a pediatric formulation that can be used in children under 6, and initiate an expanded access program. The consortium also will study pafuramidine’s effectiveness in treating the East African form of sleeping sickness. Trials to date have focused on the form of sleeping sickness found in West Africa, which is more common than its eastern counterpart.
“The progress so far of the consortium led by Dr. Tidwell is both encouraging and exciting,” said Dr. William L. Roper, dean of the UNC School of Medicine and chief executive officer of the UNC Health Care System. “The drug they discovered and developed could potentially save millions of people from a slow and very miserable death.”
Roper said the sleeping sickness project was one of several success stories stemming from UNC’s longstanding involvement in global health initiatives in Africa. Other examples include ongoing clinical trials involving HIV and AIDS patients, such as a UNC-led international study of neurological disease among HIV and AIDS patients, with sites in Malawi and South Africa.
Dr. Thomas Brewer, senior program officer for infectious diseases in the Gates foundation’s Global Health Program, said, “Sleeping sickness is one of the most serious diseases in sub-Saharan Africa. This research is exciting because it has the potential to usher in a new generation of treatment for the disease.”
The UNC-led Consortium to Develop New Drugs for Protozoan Diseases includes more than a dozen faculty and scientists from UNC, Georgia State University, the London School of Hygiene and Tropical Medicine, Ohio State University, the Swiss Tropical Institute, the Kenya Trypanosomiasis Research Institute and Immtech Pharmaceuticals Inc. Immtech is responsible for regulatory and preclinical and clinical development activities for pafuramidine required for licensure and for supplying the drug for the consortium.
“The new grant really expands what the consortium is able to do beyond what we’ve been working on for the last five years,” said Dr. Carol Olson, vice president and chief medical officer at Immtech.
The Swiss Tropical Institute is running the consortium’s clinical trials. Enrollment for the pivotal Phase III trial should be completed in December, said Dr. Christian Burri, a deputy department head at the institute.
“In parallel, the consortium will conduct a further safety study in healthy volunteers as requested by the FDA, and we will start the preparation of clinical trials in children, and in East Africa.” Burri said. “Later this year we intend to start the planning of a large scale phase IIIb trial, which will assess the safety and efficacy of DB289 under true field conditions, while the registration process is ongoing.”
The consortium established an advisory board chaired by UNC’s Dr. Frederick Sparling, with Drs. Terry Shapiro at Johns Hopkins, Ann Moore at the Centers for Disease Control and Prevention and the Gates foundation’s Brewer as board members. Laboratories involved in the discovery of the new drug candidates are run by internationally known scientists including Drs. David Boykin and David Wilson at Georgia State, Michael Barrett at the University of Glasgow, Grace Murilla at Kenya Trypanosomiasis Research Institute, Steven Meshnick and J. Ed Hall of UNC’s schools of public health and pharmacy, respectively; and Drs. Simon Croft at the London School of Hygiene and Tropical Medicine and Reto Brun at the Swiss Tropical Institute.
The original Gates foundation grant to the consortium, for $15.1 million, was announced in December 2000. That grant enabled the consortium to begin clinical trials of pafuramidine in Africa.