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On the Brink of a Watershed Moment for HIV Vaccine R&D

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Neglected Disease Funding Remains Off the Mark

M Moran, J Guzman, AL Ropars, A McDonald, L Wu, B Omune, L McSherry

 

Recent research has, for the first time, shed light on how much is being invested globally on research and development (R&D) into new products to prevent, diagnose, manage or cure neglected diseases of the developing world.

These diseases, including both well-known infections such as malaria and HIV/AIDS and less well-known diseases such as onchocerciasis and helminth infections, account for more than 11 million deaths and just under 330 million disability adjusted life years (DALYs) a year in developing countries alone. Despite this high burden, these diseases have historically received less attention than they deserve, especially in regards to funding for R&D of new pharmaceutical products. Since 2000, however, several developments have changed this field dramatically, including the establishment of new Product Development Partnerships (PDPs) for neglected diseases, increased philanthropic and public funding, and renewed commitment and participation from the pharmaceutical industry.

The research showed that more than US$2.5 billion was invested in neglected disease R&D in 2007. This funding was invested into development of drugs, diagnostics, vaccines, microbicides, insecticides and platform technologies for 30 neglected diseases of the developing world. Although this may sound like a substantial investment, it is important to remember that the cost of developing a single pharmaceutical can range from the tens of millions over 3-5 years for a new diagnostic, to hundreds of millions over 12-15 years for a new vaccine. For example, the total cost of developing a novel TB drug has been estimated at US$115 million to US$240 million , while the cost of developing a vaccine has been estimated a US$200 million to $500 million (both estimates include the cost of failure). Yet another estimate from Tufts University for the cost of developing a drug for Western markets comes in at US$403 million, again including the cost of failure. In short, as the R&D process is lengthy, risky and costly, very substantial investments are needed for a successful product to be developed.

Where does the money go?

The good news is that neglected diseases are on the global agenda and that the efforts of AIDS, TB and malaria advocates have shown results. Just under US$2 billion (almost 80 percent of total 2007 funding) went to the so-called ‘Big Three' diseases - HIV/AIDS, malaria and TB. The current portfolio of potential TB and malaria products is the largest in history. It includes, for example, advanced malaria vaccine candidates such as RTS,S (developed by GSK in partnership with the PATH-Malaria Vaccine Initiative), which has just commenced Phase III trials in seven countries in Africa. The new TB vaccine candidate (AERAS-485, being developed by the Oxford-Emergent TB Consortium), which has just begun Phase II trials in South Africa, is another example of advances in the field.

Unfortunately, however, not all neglected diseases have received attention, with many diseases that kill and disable millions of people in developing countries still remaining underfunded. Diarrhoeal illnesses - identified as one of the biggest killers in the developing world - only received US$32.5 million in 2007. This is far below what is needed to develop the new drugs, diagnostics and vaccines needed to treat and prevent the seven major diarrhoeal illnesses, such as rotavirus and cholera, which are covered by this funding.

Where does the money come from?

In its first year, G-FINDER surveyed 134 funders in 43 countries around the globe. The results revealed that a small number of organisations are bearing the brunt of funding R&D for neglected diseases. In 2007, 12 organisations provided around 80 percent of global funding, with the U.S. National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation collectively investing US$1.5 billion or 59 percent of the global total. Particularly in these uncertain economic times, it is imperative that we spread the risk so that withdrawal or reduction of funding by any one organisation will not have a detrimental impact on neglected disease R&D.

In terms of public spending, the U.S. government was the largest funder with an investment of US$1.3 billion; representing nearly three-quarters of global public spending, while the European Commission and European governments collectively invested US$384.9 million (22 percent). Also of note is the increasing role played by innovative developing countries (IDCs), with Brazil and Russia ranking as the sixth and tenth largest government funders respectively, despite their significantly lower GDPs per capita (US$5,860 for Brazil and US$7,530 for Russia, compared to US$46,040 for the US ).

The pharmaceutical industry contributed US$231.9 million in 2007, or just under 10 percent of total global funding for new neglected disease products. We note that this figure is industry's own investments and does not include funding provided by PDPs or others to industry programmes.

How can the G-FINDER data help?

The data from G-FINDER is only one element of the equation. Policy-makers and funders need to look at a range of factors in deciding where and how much to invest to maximise the health return on a given neglected disease R&D investment. Key factors in deciding which area to invest in include the severity of unmet R&D need (for instance, the burden of disease and the shortfall in existing useful products); and the severity of underfunding, with many diseases and products receiving little or no funding, as noted above.

Once a decision has been made on where to invest, the size of the necessary investment will in turn be guided by a range of factors, including:
• The type of product needed, e.g. a diagnostic, which may only need a few million dollars in funding, or an expensive full vaccine development;
• The state of the global portfolio, i.e. are there promising leads and how advanced are they already?
• The development risk, that is the likelihood that a product can be made. Scientists and companies still do not know how to make some products - a cure for the common cold being a good example - and some neglected disease products also fall into this category.

Rheumatic fever offers a helpful example of how these decision-making factors interact. Rheumatic fever is a bacterial infection, most common in children aged 5-14 years. It often leads to rheumatic heart disease, with permanent damage to the heart valves and associated risk of heart failure and stroke. According to WHO figures, rheumatic fever is the seventh highest cause of mortality from neglected diseases in developing countries, with the high death toll resulting from the lack of tertiary care facilities to treat cardiac complications in much of the developing world. A preventive vaccine for this disease is vital but does not exist. It also seems unlikely that a vaccine will be created if funders continue their current investment patterns, since the G-FINDER results showed that rheumatic fever received only US$1.7 million in 2007, well below the level needed to develop a new preventive vaccine within the next decade - or even in many decades. In other words, the severity of need and severity of underfunding are both high.

It is clear that a rheumatic fever vaccine would be the optimal product for developing country settings, avoiding the need for patients to have access to high-tech tertiary facilities for acute and long-term cardiac care. Vaccines are, as we saw, expensive to develop. However in the case of rheumatic fever, costs are likely to be lower due to a relatively low development risk. This is because the disease and its transmission are well understood, as are the science and technology to develop and produce an anti-bacterial vaccine. Limited funding over the years means that few vaccine leads are currently available and ready for further development; however, several multinational companies work in related bacterial fields and may already have suitable technologies or capabilities under way.

Based on the high need and large funding gap, investment into a preventive vaccine for rheumatic fever should be attractive for a funder who wants to invest in a lower-risk area where their money will have a high potential impact.

The Future

After past decades of inertia and neglect, the participation of many organisations and countries in the development of new products for neglected diseases is a commendable and welcome achievement.

The G-FINDER data shows, however, that these efforts are not evenly distributed, with some of the world's wealthiest countries missing in action from the top 10, top 20 or even top 50 funders. We also note that investment by some private philanthropic organisations and companies is now rivalling or exceeding spending by many public organisations, and indeed many G7 and OECD countries. While the work of these private groups is praiseworthy, we note that their efforts are meant to support, not replace, those of wealthy governments around the world.

The predominance of research into new products for HIV/AIDS, malaria and TB is understandable - and the generosity of funding is both necessary and a credit to funders. However, all neglected diseases, including these three, should receive the attention and funding needed to achieve discovery, development and registration of new products.

A broadening of funding efforts so that all who are able to contribute do so, and that all diseases receive the attention they deserve, would lead to a dramatic positive impact on the health of developing country patients afflicted with these diseases.

We hope the G-FINDER results will assist funders to identify funding gaps and see where their investments can make a substantial and valuable impact by supporting the development of new tools for neglected diseases. In tough economic times, it will be more important than ever for all funders - large and small; public, philanthropic and private; Western and developing countries - to contribute what they can to ensure that the poorest of the poor do not end up paying the price.

The full G-FINDER 2008 report is available online 

 

HO (2008) The Global Burden of Disease: 2004 update. Geneva: World Health Organisation. pp.1-146.

 

Pekar N, editor (2001) The Economics of TB Drug Development. New York: Global Alliance for TB Drug Development. Accessed 16 January 2009

Serdobova I, Kieny MP (2006) Assembling a Global Vaccine Development Pipeline for Infectious Diseases in the Developing World. Am J Public Health 22 (9): 1554-1559. . Accessed 16 January 2009

DiMasi JA, Hansen RW, Grabowski HG (2003) The price of innovation: new estimates of drug development costs. J Health Econ 22:151-185. Accessed 16 January 2009

World Bank (2007) World Development Indicators Database. Revised 24 April 2009. Accessed 11 June 2009

If you or your colleagues are active in neglected disease R&D and would like to have your contribution included in the G-FINDER survey, please contact us at: (JavaScript must be enabled to view this email address)

The authors are members of the health policy division of the George Institute for International Health.