A dramatic change in research into 10 so-called neglected diseases, including malaria, tuberculosis (TB), leprosy and sleeping sickness, could result in at least eight new drugs being developed by 2010, an influential report claims today.
After a barren period when very few therapies were introduced for these diseases, which kill around 3 million people a year, there are now more than 60 drug research projects underway.
Around three-quarters of these projects are conducted under the umbrella of drug development public-private partnerships (PPP), with 13 of them having already reached clinical trial stage and two* awaiting regulatory approval. These PPP-driven projects should result in six or seven new drug registrations in the next five years.
The 100-page report, financed by the Wellcome Trust and carried out by a team from the London School of Economics and Political Science led by Dr Mary Moran, demonstrates that PPPs have been a critical driver of this considerable increase in activity, and recommends policy-makers should support them when it comes to neglected disease research and development.
In the four years to 2004 Public-Private Partnerships spent £62m (U.S. $112 million) on a combined portfolio of 46 drug projects. In contrast, a company will have to invest around £220 (U.S. $400 million) out of pocket costs to bring just one commercial drug to market, according to the report, The New Landscape of Neglected Disease Drug Development.
The report, on the basis of a vast amount of empirical data, also finds that the PPP approach brings together the best skills of both public and private partners. This model consequently performs better than either sector working alone when it comes to delivering safe, effective, affordable drugs for neglected diseases.
Despite this, relatively little public money is given to PPPs, with just £23m (U.S. $43 million) coming from only four members of the Organisation for Economic Co-Operation and Development over the past five years. Over the same period philanthropic organizations have contributed over £111m (U.S. $200 million)
The report points out the surprising lack of policy incentives to support PPPs, which have become a cornerstone of both large and small pharmaceutical company involvement in neglected disease R&D. And, it adds, some of those that are on offer could well be counter-productive.
The report warns, Continued lack of public support is likely to lead to the collapse of PPPs, leaving governments with little recourse but to fund expensive in-house industry activity from start to finish or to build alternative drug-making capacity.
There are currently five PPPs** concentrating on drugs for neglected diseases. All, apart from one, which is operated by the World Health Organization, were set up in the last six years, therefore they have not had time to establish a track record in bringing drugs to the market. However, the report points out, PPPs now conduct the majority of neglected disease drug projects, have the majority of drugs in clinical trials and are likely to have registered several products within the next few years. This is an excellent outcome for a very modest annual investment of philanthropic and public funds.
Moran and her colleagues also describe how multi-national pharmaceutical companies, which had moved away from neglected disease research, have now returned to this area on a no-profit-no-loss basis. Eight are involved in this type of research, with four having dedicated institutes employing over 200 scientists.
These companies are not motivated by commercial returns in neglected disease markets but rather by longer term business concerns, including managing reputational risk, addressing ethical issues and positioning themselves strategically in growing developing country commercial markets, the report explains.
Between 1975 and 1997 only 13 new drugs were developed for neglected diseases. But that was when the WHO and multi-national companies were alone in working on this problem. Now they are involved in more than half the 63 projects which are underway, sixteen of which are joint ventures with PPPs.
Morans team recommends the creation of a public fund to pay for research and development of neglected disease drugs within PPPs, which they estimate would cost up to £1bn (U.S. $1.9 billion) during 10 years.
They also urge a package of incentives to encourage research by small or medium sized companies, who are increasingly becoming players in the neglected disease field.
Moran, program director of the Pharmaceutical Research and Development Policy Group at the LSE, said, For many years, it was the sad truth that virtually nothing was happening in neglected disease R&D. But we are now seeing some really promising developments that simply did not exist 10 years ago. In reality, the current problem is not that nothing is happening it is that policy-makers and government donors are still working off this old R&D script. As a result, policies have tended to focus on how to get R&D started but have largely failed to support neglected disease initiatives that are already working on -- and in some cases already delivering new drugs. We hope our report goes some way towards bringing this R&D script up to date. With the right information and tools, we are confident that policy-makers can give a highly-effective boost to neglected disease drug development for the millions of patients who are waiting on these products
Dr. Ted Bianco, director of technology transfer at the Wellcome Trust, commented, This report gives us confidence that PPPs are stimulating an unprecedented level of research into badly needed, new drugs for neglected diseases. It is evident that this model has attractions for small and large companies alike and most importantly looks set to deliver much needed medicines to some of the most under-privileged people of the world. There is a political consensus within the G8 that it is a global responsibility to check the misery caused by infectious diseases in developing countries. Dr Morans proposals on how governments may more fully engage with the PPPs is timely particularly as the philanthropic organizations cannot be expected to shoulder the financial burden of this type of research forever.
Dr. Chris Hentschel, chief executive officer of the Geneva-based Medicines for Malaria Venture, observed, "In public policy, just as in drug research, we need to rigorously follow the evidence of what works and what does not. Few who know this area will be surprised at the conclusion of this report which is supported by data meticulously compiled and analyzed. Public policy initiatives supportive of the burgeoning PPP pipelines need to be implemented quickly otherwise the enormous value already created in them may be lost."
* Rectal artesunate for malaria and paromomycin for visceral leishmaniasis.
* PPPs :
Medicines for Malaria Venture, founded 1999.
TB Alliance, founded 2000.
Institute for OneWorld Health, founded 2000
Drugs for Neglected Diseases Initiative, founded 2003.
WHO/ Special Programme for Research and Training in Tropical Diseases, founded 1975.
Neglected Diseases as Listed by the World Health Organization:
Human African Trypanosomiasis ( HAT or sleeping sickness): Around 60m people in 36 sub-Sahara African countries at risk. Reduces many victims to zombie-like state. Fatal if not treated. Most drugs are old, difficult to administer and one Melarsoprol contains arsenic and can kill up to one in twenty patients.
Chagas disease : Prevalent in South and Central America as well as Mexico, affecting 16-18 million people in 21 countries with 120m at risk. Is often symptomless for years but can eventually cause heart damage and kill. Two drugs available for treatment but these can have serious and frequent side-effects.
Dengue: More than one-third of the worlds population 2500 million people are under threat from this mosquito-borne disease which is nicknamed breakbone fever because of the crushing intensity of the flu-like symptoms it brings. Affects 100 countries in Africa, the Americas, SE Asia and western Pacific. No specific treatment.
Leishmaniasis: Has spread significantly in the last decade and now affects 88 countries with 350m people at risk. In worst cases it causes severe scarring and eats away the mouth, palate and nose tissue, leading to victims being ostracised by their communities. Transmitted by sandflies. Drugs are either toxic or unaffordable.
Leprosy: Earliest reported cases in 600 BC. Over past 20 years more than 12m patients have been cured and the disease has been wiped out in 108 of the 122 countries where it was a threat. However in 2002 there were still 650,000 cases reported in India, Brazil, Madagascar, Mozambique, Myanmar and Nepal. Effective drugs have been available since the 1940s but an extended course is needed.
Lymphatic filariasis (Elephantiasis): This mosquito-spread disease causes massive swelling of the limbs and genital area. Of the 120m people who have it around one-third are seriously incapacitated or disfigured. Two-thirds of cases occur in India and Africa with the rest in S. Asia, the Pacific and Americas. It is a continuing problem but drugs can be effective if given early enough. Some have been donated by major pharmaceutical companies (GlaxoSmithKline and Merck).
Malaria: There are more than half a billion episodes a year resulting in at least one million deaths. Most victims are young children. The majority of cases occur in Africa with nearly 25 percent in SE Asia and the western Pacific. Malaria is estimated to cost Africa alone $12 billion in lost GDP each year. Extensive resistance to some drugs has now prompted the WHO to recommend combination therapies, preferably those containing derivatives of artemisinin taken from the Chinese herb qinghao -- but these can be expensive.
Onchocerciasis (River Blindness): One of the worlds leading causes of infectious blindness, caused by a parasitic worm which lives in the body for up to 14 years. Some 18m people in tropical Africa are infected. Of these 800,000 have vision impairment and another 270,000 are blind. A single dose of ivermectin, taken annually, is effective but does not completely clear the infection. This drug is being donated free by Merck.
Schistosomiasis (Bilharzia): Affects 200m people living in 74 developing countries. Parasite picked-up from snails living in freshwater causes damage to the bladder and kidneys. Kills relatively few around 15,000 but children are especially vulnerable. Two effective drugs are available praziquantel and oxamniquine.
Tuberculosis: Kills around 1.6 million people a year with someone becoming infected every second. They, in turn, will infect between 10 and 15 people. The WHO declared TB a global health emergency in 1993. Most cases occur in Africa, SE Asia and the western Pacific. Various vaccines are in development and the disease can be effectively treated with a cocktail of drugs, but only after several months of intensive therapy.
Source: Wellcome Trust