A private-public partnership to establish a not-for-profit research organization focused the discovery of drugs to treat resistant strains of tuberculosis in an odd way has its genesis in the death priest of a in Boston and a shantytown in Peru.
Eli Lilly is committing $15 million to establish The Lilly Not-For-Profit Partnership for TB Early Phase Drug Discovery to be based in Seattle, Washington. The pharmaceutical giant will fund the laboratory space, equip the facility with drug screening and testing equipment and provide a library of more than 500,000 compounds for screening as possible TB treatments. The partnership will bring together Lilly experts in medicinal chemistry with academics with expertise in microbiology, genetics and molecular biology.
The National Institute of Allergy and Infectious Disease, which is currently funding more than 70 projects focused on TB drug development, will partner with the not-for-profit to help identify the most promising drug candidates for further development. Other partners contributing to the effort include Merck, Jubilant Biosys, Afya World Medicines, the Infectious Disease Research Institute, the Seattle Biomedical Research Institute and the University of Washington Department of Global Health.
"It addresses the problem of the difficulty in getting a robust pipeline of drugs for a disease that requires a robust pipeline because of its tendency to evolve into a resistant form," said Anthony Fauci, director of the National Institute of Allergy and Infectious Disease. "Whenever you have a microbe that has a tendency to evolve into a resistant form, one of the best ways around that is to have a robust pipeline."
Tuberculosis is a contagious disease of the lungs caused by airborne bacteria. An estimated 2 billion peopleone third of the world's population—is infected with the bacteria that causes TB. One in ten of those will become sick with active TB during their lifetime. A total of 8.8 million people are stricken with the disease each year and 1.6 million died from it in 2005. Of particular concern has been the rise of multi-drug resistant TB and more recently extremely-drug resistant TB, which has posed greater challenges to fighting the disease as existing regimes of drugs are rendered ineffective.
Though the Lilly effort is not unique in its public-private approach, those involved in TB research and drug development said it is noteworthy because of it breadth and the fact that it is an effort initiated and drive by a pharmaceutical company.
"We all realized that you needed new drugs for the treatment of TB because of multi-drug resistant TB but now you have a far greater situation in that you have evidence that there are strains that are circulating that are resistant to even most second line drugs," said Gail Cassell, vice president of scientific affairs and an expert on infectious disease who is leading the effort for Lilly. "The urgency and the need for development of new drugs for the treatment of TB are really critical."
Fighting Resistant TB
Lilly's most recent effort around TB follows its acquisition of Bothell, Washington-based ICOS this year. After Lilly acquired the maker of the erectile dysfunction drug Cialis, it also found it had a team of ICOS researchers who wanted to apply their chemistry experience to discovering drugs for neglected diseases. The decision to launch the drug discovery effort around TB builds on Lilly's earlier efforts to fight TB in some of the world's most afflicted areas, an effort that essentially began through happenstance.
In 1997, Paul Farmer and Jim Yong Kim found themselves in Carabayllo, an impoverished district on the outskirts of Lima, Peru. The two Harvard-trained doctors, who co-founded the nonprofit Partners in Health, were there because of their friend and supporter Father Jack Roussin, a Boston priest who returned home from a trip to Peru and died seven weeks later from Multi-Drug Resistant TB or MDR-TB.
At the time, the World Health Organization did not view MDR-TB as a big problem. The agency didn't believe it was cost effective to try to treat people with the disease in poor areas. But Farmer and Kim disagreed. They saw a potential health care crisis unfolding and a way to address the problem.
The pair adopted a system they had developed of training local people to monitor patients in their homes and ensure they complied with their drug regimens. Their 85 percent cure rates surprised the medical establishment. It also ended up changing the view of the WHO and others about treatment of MDR-TB.
But getting access to the costly second line drugs needed to fight the disease had been a problem. When Partners in Health boardmember Howard Hiatt, the former dean of the Harvard School of Public Health, learned of the financial problems the organization faced getting the necessary drugs, one of the calls he made was to a friend on the board of Eli Lilly. Two of the drugs that were among those in the second line of defense against TB were Lilly products. These antibiotics were about 40 years old and generated about $5 million in revenue a year for the company. But they were still produced because of the unique role they played as a second line treatment for TB.
A Potential Model
In 2003, to meet the demand, Lilly made the decision to transfer all of the technology to produce the drugs to partners in countries that faced the highest burdens from TB, including South Africa, Russia, China and India. The company didn't just transfer the technology and know-how for producing the two antibiotics. In some cases, it also purchased new equipment for these partners to manufacture the drugs and trained them in good manufacturing processes. Lilly, which by this time had exited the infectious disease area, derives no financial benefits from the drugs and will have no intellectual property claims for the drugs developed through the not-for-profit.
To date, not counting the newly launched drug discovery effort, Lilly has spent $120 million in its TB efforts. The Global Alliance for TB Drug Development, a not-for-profit that has won backing from the Bill & Melinda Gates Foundation and several governments, will take promising compounds discovered by the Lilly not-for-profit and advance them through clinical development.
Maria Freire, CEO of the TB Alliance said while there are other public-private partnership for drug development, the Lilly effort is unique in its focus on discovery stage. The discovery stage is an area of acute need since the economics of producing drugs for TB has made it an area that major pharmaceutical companies in developed countries are not pursuing. Even if there is encouraging basic science, one gap in the development of new drugs is the absence of investment to advance those initial discoveries to a point where they could be read to enter pre-clinical or clinical testing.
"Could it serve as a model for other neglected disease? Yes, I think it could," said Freire. "Could Lilly in the process of doing this expand it to other diseases? Yes. It would be nice to have this project take hold and become a model."