Chapter 8.1 CS3: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Priority Medicines For Europe and the World"A Public Health Approach to Innovation"
Background Paper for Review
Public-Private Partnerships for Neglected Diseases:
Opportunities to address pharmaceutical gaps for neglected diseases
CASE STUDY 3
Global Alliance for TB Drug Development
(TB Alliance)
By Elizabeth Ziemba, JD, MPH
7 October 2004
Case Studies and Needs Assessment of Four Public-Private Partnerships
Global Alliance for TB Drug Development (TB Alliance)
Introduction:
The Global Alliance for TB Drug Development (TB Alliance or GATB) is a nonprofit, public-private partnership organization dedicated to the discovery and development of new, faster-acting and affordable drugs to fight tuberculosis (TB). Established in 2000, the TB Alliance catalyzes global TB drug development and develops a portfolio of promising anti-TB drugs through innovative partnerships involving public, private and academic research worldwide.[1]
History of TB Alliance:
The TB Alliance was conceived at a February 2000 meeting in Cape Town, South Africa, hosted by the Rockefeller Foundation and the Stop TB Partnership, where 120 representatives from public health, development aid, research, academia, industry and non-governmental organizations gathered to discuss the problems of tuberculosis treatment. Participants stressed the need for new TB drugs and highlighted the unprecedented scientific opportunities, public health imperative and economic rationale for developing new TB treatments. The resulting "Declaration of Cape Town" provided a road map for TB drug development and led to the creation of the Global Alliance for TB Drug Development (TB Alliance), now headquartered in New York City, with offices in Brussels, Belgium and Capte Town, South Africa.[2]
The formation of the TB Alliance was driven by the need to halt the increasing spread of TB whose control efforts were hindered by the lengthy and cumbersome regimen imposed by old drugs. Research and development in this field had come to a virtual standstill as the last novel anti-TB compoundwas introduced in 1970 and anti-TB programs winded down even before antimicrobial research at large TB does not get the attention it deserves because its victims are often poor, with the highest disease burden in developing countries, so there is a lack of financial incentive for pharmaceutical companies to invest in the development of new medicines to treat this disease.
The rapid spread of the disease, the growing the lack of effectiveness of existing old medicines, and the increasing resistance to the current treatment regimens are contributing to this global health crisis that the Global Alliance for TB Drug Development is working to solve.
Mission:
The mission of the TB Alliance is to accelerate the discovery and/or development of cost-effective new drugs that shorten or simplify treatment of TB, provide effective treatment of multi-drug-resistant TB, improve the treatment of latent TB infection, and can be made affordable and accessible in TB endemic countries. 1
According to its website[3]:
“We are building a portfolio of promising drug candidates and forging innovative partnerships in order to deliver a new anti-tuberculosis drug in a decade.
Asa not-for-profit enterprise, we enlist the best practices, science and resources of the private and public sectors the world over to meet this urgent health need.
Our mission is to ensure equitable access to a new, faster tuberculosis cure that will advance global health and prosperity. “
In support of its mission the TB Alliance joins forces with other organizations to catalyze science and industry; rallies governments and policymakers; and mobilizes health and advocacy communities.[4]
Notably, this endeavor is supported by the World Health Organisation: the Stop TB Partnership appointed the TB Alliance as the lead agency of its Working Group for TB drug Development and integrated the search for such new tools as a cornerstone of its Global Plan to Stop TB.
“Now that we have the Global Plan, the world must invest in better treatment today and tomorrow. If we fail to back such a simple roadmap, future generations will remember us, not for stemming the tide, but for choosing to permit an airborne contagion to team up with HIV and sweep the globe.”
Dr. LEE Jong-Wook, Director-General,World Health Organization, 2003
Disease Rationale:
The worldwide resurgence of tuberculosis (TB) is extensively documented: Every fifteen seconds, a person dies from TB; one third of the world’s population is already infected with TB; every second someone in the world becomes newly infected with TB.[5] The top ten endemic countries are: India, China, Indonesia, Nigeria, Bangladesh, Pakistan, Philippines, Ethiopia, South Africa, and the Russian Federation.5 With increases in travel, mass transportation and population displacement, TB is everywhere including Europe and North America.5
Tuberculosis is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria usually attack the lungs and are easily spread through the air when a person with an active case of TB coughs or sneezes.[6] Individuals with weak immune systems such as individuals with AIDS are particularly susceptible to TB. HIV infection is the most potent risk factor for converting latent TB into active transmissible TB.[7] – accelerating the spread of the disease - while TB bacteria help accelerate the progress of the AIDS infection in the patient. Today TB is the leading cause of death in persons who are HIV positive.
Treatment consists of a six to nine month course of medicines. Daily oral doses of multiple drugs that may include combinations of rifampin, isoniazid, pyrazinamide, ethambutol, or occasionally others, are continued until the patient is cured.[8]
The expense or availability of the medicines as well as the lengthy course of treatment impacts this regimen. Once patients feel better, they may stop taking the medicines. Unfortunately, more than two- thirds of TB patients do not receive full and proper treatment, further fueling the spread of deadly multi-drug resistant strains (MDR-TB) have emerged.
MDR-TB cannot be adequately treated through the standard short-course therapy, so treatment requires up to 2 years of "second-line" drugs. These drugs are often toxic, expensive and ineffective, since no new drug has been introduced in thirty years. The costs can be staggering - up to 1,400 times the cost of regular treatment. Many MDR-TB cases defy a cure.
Areas where MDR-TB is a serious problem include Estonia, Latvia, and China’s HenanProvince. MDR-TB strains also are appearing in significant numbers in Mexico; cases also appear to be increasing in Denmark and Germany
According to the World Health Organization, Global Tuberculosis Control Report, 2001[9], the number of cases by region has grown and is projected to grow as follows:
Table 8.1. Estimated Number of Tuberculosis Cases by Geographic Region
Global Tuberculosis Control WHO Report, 2001, WHO/CDS/TB2001.287, page 42,
accessed 5 May 2004.
As discussed in other sections of this report, tuberculosis and multiple drug-resistant tuberculosis is a growing health problem in the European Union, particularly the expanded European Union.
Impact of New Drugs
With the new drugs targeted by the TB Alliance, the improved treatment regimen will become the cornerstone of future TB control and accelerate the path to reversing the epidemic, because it will:
- Improve DOTS. By shortening or simplifying therapy, a new regimen will enhance the effectiveness of DOTS programs, improve patient compliance, and thereby increase cure rates.
- Accelerate access to TB treatment and TB control. A shorter TB treatment will dramatically facilitate DOTS implementation and will offer a cost-effective mechanism to expand DOTS in resource-scarce settings. Currently, only one third of patients worldwide are treated under DOTS yet TB control rests on effective treatment of active cases.
- Control MDR-TB.By effectively treating resistant strains, a new drug will have a profound impact on the life of MDR-TB patients. A more effective MDR-TB drug will reduce the length of treatment, thereby increasing compliance among MDR patients and decreasing the emergence of super MDR organisms--those resistant to virtually all known anti-TB drugs.
- Combat HIV. HIV and TB have become twin-epidemics and TB is now the single largest cause of death in AIDS patients. With carefully tested new drugs, the simultaneous administration of anti-TB (ATB) and antiretroviral (ARV) drugs will no longer be hindered by incompatible regimens. Furthermore, a short-acting drug regimen will play a critical role in effective HIV care and prevention.
Current Organizational Composition, Partners, and Funding:
Organization
The TB Alliance’s business model of a public-private partnership is predicated on lean, efficient operations of a small biotech, with a social mission. In addition to a Chief Executive Officer, who leads the organization and is a member of the Board, the TBAlliance management structure includes Directors of R&D, Advocacy and Public Affairs, and Finance and Administrationsupported by a small staff and developing activities worldwide through a network of partners. A Stakeholders Association and a Scientific Advisory Committee provide guidance and support to its activities.[10]
The Board of Directors
A Chief Executive Officer leads the organization and is a member of the Board. The Board of Directors assumes fiduciary responsibility for the TB Alliance and guides the business strategy, reviewing its strategies, actions, and budgets. The Boardconsists of seven to thirteen directors, elected for staggered three-year terms. Currently, the TB Alliance’s Board has eleven members, representing international and national government agencies, pharmaceutical and biotechnology companies, private foundations and non-governmental organizations.10
Please refer to Annex 8.1.3, Section C for a list of members of the Board of Directors.
Stakeholders Association
The TB Alliance also includes in its governance framework a group of institutions that join in a "Stakeholders Association" and have certain roles and responsibilities of advising, guiding and supporting the organization. Provisions were made for close coordination between the TB Alliance, its Board of Directors, and its Stakeholders; including the election of a member of a Stakeholders representative to sit ex-officio on the Board of Directors. Stakeholders represent the breadth of institutions worldwide that share a clear interest and, a significant stake, in ensuring the development of new TB drugs through the Alliance. They include representatives from developing nations, governments, NGOs, foundations, industry, and other significant contributors to the fight against tuberculosis.[11]
Please refer to Annex 8.1.3, Section C for a list of members of the Stakeholders Association.
Scientific Advisory Committee
The TB Alliance established a Scientific Advisory Committee to assist in evaluating proposals and projects under consideration for investment as part of its TB drugs portfolio. Members of the Scientific Advisory Committee are selected for three-year terms. To address myriad scientific and technical needs, the Chair has the flexibility to invite scientists to serve as ad hoc members for limited periods of time or on a project-by-project basis. The Scientific Advisory Committee provides technical expertise on drug research, development, manufacturing, and distribution, as well as othermedical and scientific issues, and consists of 15 scientific experts from a wide range of relevant disciplines, including, basic science, clinical expertise, drug development and ethics, among many others.[12]
Please refer to Annex 8.1.3, Section C for a list of members of the Scientific Advisory Committee.
Management Team and Staff
While operating on several continents, the TB Alliance maintains a lean organizational structure, adding resources as needed. This model allows it to be nimble and proactive, allowing it to continuously survey possible novel TB drug candidates and selectively intervene to move a drug candidate through development and ultimately to regulatory approval and registration.[13]
Please refer to Annex 8.1.3, Section C for more information about the Chief Executive Officer, Dr. Maria Freire and the staff of the TB Alliance.
Partners
TB Alliance has mobilized numerous partners in the drug development and funding process. By entering into public-private partnerships, the organization stimulates and leverages the basic research, discovery and development work carried out in industry, universities, and public and private research and clinical laboratories worldwide to ensure that promising drug candidates will move rapidly along the development "pipeline" to the patients in need. Detailed descriptions of specific partnerships and pipelines projects are provided below.
TB Alliance has received support including funding and in-kind donations such as expertise from the Bill & Melinda Gates Foundation, Rockefeller Foundation, Netherlands Ministry for Development Cooperation, U.S. Agency for International Development,World Health Organization, National Institute of Allergy and Infectious Diseases (National Institutes of Health), Centers for Disease Control and Prevention, GlaxoSmithKline, Bristol Myers Squibb Foundation , Medical Research Council of South Africa, and Research Triangle Institute.
Funding
The TB Global Alliance has succeeded in raising more than $ 42 million from various public and private sources as of August 2004, and is finalizing and additional $8 million grant from USAID.
These funders and amounts are as follows:
DONORS / TOTAL (USD)Bill & Melinda Gates Foundation / 25,000,000
Rockefeller Foundation / 15,000,000
USAID / 8,000,000
Dutch Government
and World Health Organization (WHO) / 2,000,000
Bristol Myers Squibb Foundation / 150,000
TOTAL in grants / 50,150,000
Additional in- kind contributions (US National Institutes of Health) / 2,100,000
Initiative on Public-Private Partnerships for Health website
accessed 5 May 2004. Revised by TB ALLIANCE AUG 2004
No funds in support of this partnership have been received from the European Union.
Strategy and Pipeline Overview
Strategy
In order to address the market failures that produced a dearth of research and development to support new tuberculosis medicines, the TB Alliance is working towards solutions as a public-private partnership ensuring that anti-TB candidates are identified in public and private laboratories worldwide and move quickly through all stages of development.
The TB Alliance takes a two-pronged approach to its research and development strategy: (1) Building and managing a portfolio of promising anti-TB compounds whose development is outsourced to public and private collaborators worldwide and (2) Identifying and supporting projects that address critical infrastructure gaps and help to streamline the process for the successful registration of anti-TB medicines.[14]
The TB Alliance is building a solid portfolio of projects at the lead identification, lead optimization, preclinical and clinical development stages. Through competitive requests for proposals and active scouting, the TB Alliance identifies the most promising drug development projects. After scientific and technical due diligence, it selects project investments to enhance and strengthen its pipeline, thereby increasing the chances of success. It also actively engages with industry to advance TB drug development beyond its own portfolio.
A specific, technical development plan with clear timelines is established for each compound/project selected for the portfolio. The development plan includes a series of milestones, each designed to prompt a go/no-go decision that determines whether development continues. In a model already proven in industry, the TB Alliance outsources these activities, or engages in collaborative development with pharmaceutical research and development partners, but retains control of the management oversight, closely monitoring and evaluating progress at every stage.
To expedite registration of new medicines and to keep costs down, investments are leveraged by:[15]
- Outsourcing to cost-effective contract research organizations, companies and/or other highly qualified technical/scientific institutions worldwide;
- Obtaining in-kind contributions from public and private sector collaborators and partners;
- Actively monitoring each stage of the R&D pipeline through dedicated project management;
- Creating synergies between and among critical partners in drug development, particularly in the pharmaceutical industry;
- Capitalizing on new scientific advances, such as the sequencing of M. tuberculosis, combinatorial chemistry, and other developments;
- Pursuing creative licensing and intellectual property agreements;
- Reducing the cost and length of clinical trials by obtaining regulatory fast- track status, conducting clinical trials where the necessary volume of patients already resides, and an efficient and proactive management process.
By combining public resources, both technical and financial, with private sector expertise and know-how[16], the TB Alliance leads the drive to develop a solid portfolio of therapeutic alternatives and bring a new TB drug to the market by 2010.
Pipeline
Since 2000, the TB Alliance has catalyzed the expansion of the TB drug pipeline, now encompassing 20 drug R&D projects, by taking the lead or partnering on the development of seven projects at discovery, development and clinical stages,and actively negotiating for an additional nine.
The following chart represents the global drug development pipeline as of mid 2004:
[The following section is an excerpt from the website, accessed 5 May 2004]
The TB Alliance has assembled a portfolio of promising anti-TB compounds and is overseeing their development. The compounds, which were carefully selected through TB Alliance business development initiatives including requests for proposals (RFPs), span the lead identification, lead optimization, and preclinical development phases. The portfolio reflects the TB Alliance strategy to engage expertise and resources in every discipline worldwide from academia, industry and public laboratories.
8.1 CS3-1
Chapter 8.1 CS3: Public-Private Partnerships for Neglected Diseases
Opportunities to address pharmaceutical gaps for neglected diseases
Table 8.1.5 TB Alliance Product Portfolio17