Antimalarial Drug Venture Aims to Succeed
At the National Foundation for Infectious Diseases 2004 conference, held this week in Bethesda, Md., Bridget M. Ogilvie used the case of antimalarial drugs to illustrate how to stimulate the research and development of products with "no market pull."
Ogilvie is chair of the Medicines for Malaria Venture (MMV), a Swiss-founded nonprofit foundation whose stated goal is "to bring public and private sector partners together to fund, and provide managerial support for the discovery and development of new medicines for the treatment of malaria."
"We're really in trouble with malaria because it's on the rampage again," Ogilvie said. She attributed the disease's resurgence to "the onset of antimalarial drug resistance" that began in the late 1970s.
According to MMV, malarial parasites infect a million people each day and kill one person every 30 seconds. Ogilvie said that the disease is responsible for one of every five deaths of African children less than five years old.
Chloroquine and sulfadoxine-pyrimethamine, antimalarial drugs used to combat the disease in the developing world, "are becoming virtually useless through resistance" in the malarial parasite Plasmodium falciparum, Ogilvie said. Although three other antimalarials have been developed since 1975, Ogilvie said they are too expensive for those who live in areas where malaria is endemic.
MMV, which was founded in November 1999, has set ambitious goals for the development of new antimalarial drugs.
"We, of course, want drugs that are efficacious against drug-resistant strains and which will cure within three days, because we know compliance will not happen if you expect people to take a drug for more than three days in the environments in which we are forced to operate," Ogilvie said. "We want to hopefully have a drug with a low propensity to generate rapid resistance. It will be safe in small children and pregnancy and have appropriate formulations and packaging to use in these countries."
"Above all, low cost of goods is absolutely crucial," Ogilvie said. She said MMV is "hoping to have treatment which is less than a dollar" over three days.
Despite setting the bar high, MMV has identified and funded 21 drug-development projects in the past four years. MMV identifies drug candidates through worldwide solicitations and has funded four rounds of grants so far. Project selection involves choosing a likely antimalarial candidate and selecting industrial partners to develop the drug.
Ogilvie said that candidate antimalarials will be formulated as "fixed combinations of at least two molecules in order to prevent resistance," as mandated by the World Health Organization.
Two MMV products are currently in Phase III clinical trials. MMV expects to file for regulatory approval of its lead product in 2006 and receive marketing approval in malaria-endemic areas by 2007.
MMV's lead product is a pediatric formulation of artemether with lumefantrine, or Coartem, which Novartis already supplies to the World Health Organization in a formulation for adults.
Ogilvie said that part of the process for developing a pediatric formulation of Coartem—a venture mostly funded by Novartis—involves palatability studies "to get something which has an acceptable taste to African children."
Most of the products MMV supports are in the exploratory or preclinical stages of development. "We have eight new therapeutic targets now in the pipeline, which is a bit of a surprise to me," Ogilvie said. "When I first took on this role as chairing this organization, my first worry was whether or not there would be enough science out there" to support drug development.
As products are brought to market, MMV will retain the rights to the drugs for the prevention and treatment of malaria in areas where the disease is endemic. "The industrial partner will retain the rights for the traveler's market and any other indications that come up in the future," Ogilvie said.
MMV has benefited enormously from grants from the Bill and Melinda Gates Foundation, which Ogilvie said has "transformed the outlook for diseases of this kind across the world."
The Gates Foundation awarded a $25 million grant to MMV in 2000 and last year pledged an additional $40 million over five years. Today, grants from the foundation account for 61 percent of MMV's total funding.
Ogilvie said that MMV also benefits immensely from the support of scientific advisers and a board of directors who "work on a pro bono, expenses-only basis." The organization also has extensive contacts in the pharmaceutical industry worldwide that receive MMV funding but also provide in-kind support to help the organization meet its goals.
"The staff working on these projects in the pharmaceutical companies absolutely love" to work on the antimalarial projects, Ogilvie said.
"It is extraordinary how everybody's come to the party on this one," she added. "I couldn't have predicted this when we began."