Cookie policy: This site uses cookies (small files stored on your computer) to simplify and improve your experience of this website. Cookies are small text files stored on the device you are using to access this website. For more information please take a look at our terms and conditions. Some parts of the site may not work properly if you choose not to accept cookies.


Subscribe or Register

Existing user? Login

FIP 2008: How public private partnerships are aiding discovery for neglected diseases

Lin-Nam Wang reports on congress keynote lecture at the World Congress of Pharmacy and Pharmaceutical Sciences, which focused on examples of successful partnerships in tackling neglected diseases

by Lin-Nam Wang

Lin-Nam Wang reports on congress keynote lecture at the World Congress of Pharmacy and Pharmaceutical Sciences, which focused on examples of successful partnerships in tackling neglected diseases


How is it that, according to recent figures, almost two million people each year die from diarrhoeal disease, asked William Charman, professor of pharmaceutics at Monash University, Melbourne, Australia. Yet this is the situation.

One issue is access — many of the 14 million people who die each year from infectious diseases, which are often tropical diseases, would still be alive today if only they had had access to essential medicines, he said. The numbers are clearly unacceptable, but to have been collected, the people who have died would have had to have access to a medical centre.

There are many people in the world who do not have access to an infrastructure that results in a diagnosis, so “undoubtedly, these unacceptable figures are an under representation”, he said.

William Charman:  public private partnerships are an effective mechanism to discover new medicines

Professor Charman went on to outline the issues of neglected diseases, which include malaria, leishmaniasis, onchocerciasis and filariasis.

First, he emphasised their link with poverty. “Even if we had treatments, that alone would be insufficient. It is essential that we look at [poverty and neglected diseases] in consort. …

“Even though, from a pharmaceutical standpoint, we have the responsibility and opportunity in terms of discovery of medicines and vaccines, we need to recognise there has to be an impact on poverty: economic circumstances, education and good government are important,” he said.

There also has to be an opportunity for neglected populations to trade their way out. And as for farm subsidies that are an issue in European and US politics, “Let me state that those subsidies have a direct impact on poverty,” he commented.

Neglected diseases are a common term, but we generally forget that these diseases impact on neglected populations — those who do not have access to the health infrastructures that are taken for granted in the first world, he explained.

Don’t blame the industry

Between 1975 and 2000 only 13 drug products were developed for the World Health Organization’s list of 10 neglected diseases. “So you can see that there is not really an appropriate effort,” Professor Charman said.

In the past, large pharmaceutical companies had a role in drug development for neglected diseases, but all of these have either pulled back and most have pulled out from this essential field. Contributing factors to the undermining of these efforts include political decolonisation and corporate consolidation.

Most significantly, the standard commercial returns expected by the pharmaceutical industry do not exist in this field — the free market system fails to provide an adequate incentive, he explained.

However, he maintained that it is inappropriate, simplistic and short-sighted to suggest that the industry should work in this area because it is the right thing to do. “It might be the right thing to do from the standpoint of discovery and development, but it is not the right thing to do from the standpoint of shareholders in those companies,” he said.

“Many of us are investors in these companies, either directly or through our retirement funds. The current free enterprise model is not consistent with undertaking discovery for neglected diseases,” he added.

The solution, therefore, is to find a different model of engagement — a different way of working in partnership in order to tackle the discovery and development of medicines for these neglected diseases, he said. One such model is public private partnership (PPP) — private industry working with public bodies.

This concept is not a new one and, in fact, can traced back to 1975 when the WHO tropical disease research programme was established by the United Nations, the World Bank and the WHO, to undertake broad based public sector health programmes in disease endemic countries, working with private organisations, although the term “PPP” was not used, Professor Charman said.

High impact outcomes that have resulted from these partnerships include the Mectizan programme, which was initiated in 1987 by the WHO, Merck and others, to prevent river blindness (onchocerciasis). This disease is spread by blackflies, particularly in river deltas.

Unfortunately, a lot of people in pharmacy and pharmaceutical science are not familiar with the Mectizan (ivermectin) story, Professor Charman said. Through this programme, over 530 million doses of the treatment have been distributed. A single dose of ivermectin once a year, treats onchocerciasis and prevents river blindness from developing and 1.8 billion tablets have been donated by Merck.

The drug company has been involved in this programme for many years and the history of how this programme was set up gives a good insight into how PPPs can be put together, he said.

“Unfortunately, the public do not associate this with Merck. They associate other things [with the company] and we need to change this, he said. “Every pharmacy student in the world should know about these things, know what medicines can do and what partnerships can do,” he added.

Another programme, involving Glaxo-SmithKline, Merck, WHO and endemic countries, has a target to distribute six billion doses of albendazole and ivermectin to treat lymphatic filariasis by 2020. To eradicate this disease would require 1 billion people — one in every five people on the planet — to be treated, free, once each year, for five years — something which Professor Charman called “an audacious goal”.

However, in terms of medicines discovery, PPPs are relatively new, beginning in the 1990s. Although the approach is a natural extension of the treatment programmes that already exist, Professor Charman told the audience: “I don’t want you to leave this room thinking [discovery and development] PPPs are straightforward and well established. At most, they’ve only been going for eight years [the most advanced one being for malaria — see Panel].

“They are very much an evolving model — a work in progress.” He said that these partnership programmes are taking the best they can from industry as well as academics and broader public organisations.

“It is essential that we learn from industry and adopt best practices regarding target validation, hit selection, lead optimisation and portfolio management,” he said.

The three main examples in terms of drug development PPPs are:

  • The Medicines for Malaria Venture
  • The Drugs for Neglected Diseases Initiative
  • The Global Alliance for TB Drug Development

Because this approach has been put in place with regard for the way in which industry is involved and is able to contribute, more companies are getting involved. Seven of the leading 12 companies now have some degree of involvement with these PPPs, with the European companies (GSK, AstraZeneca, Novartis and SanofiAventis) being most visible. The companies are involved on a no-profit/no loss model. They are motivated by corporate social responsibility, he explained.


Since 2000, more than 75 per cent of new drug candidates for neglected diseases have come through the PPP mechanism. Professor Charman then quoted some compelling statistics: of the three PPPs listed, along with the Institute for One World Health, 46 projects have been advanced over five years. Analysis by the London School of Economics shows that US$112m has been spent progressing these projects.

“That is a relatively small amount to be spread across 46 projects,” he said. He added that most outstanding was that the progress of these projects occur along timelines similar to those for commercial medicines, although part of the reason for this fairly rapid progress is that the drugs are for acute treatments rather than long-term ones.

Of these projects, there is the expectation that, by the end of 2010, eight new drugs will be registered — “a pretty significant outcome”. However, Professor Charman warned that issues ahead include regulatory and safety approval, and ensuring a reasonable cost of the medicines as well as continued and sustainable funding.

He said that none of these programmes would exist without the Bill and Melinda Gates Foundation and called the influence of the Gateses “a transforming influence”. However, at the moment, this foundation provides more than 60 per cent of the funding.

“No enterprise can be that dependent on a single source of funding. The commitment of Bill and Melinda Gates is palpable. It is not only their money, but their personal commitment in this area that is allowing some of these outcomes to come through.

However, in the future for PPPs, the funding has to broaden out. The world cannot depend on the Gates Foundation to support work in this area. Governments from around the world need to contribute and there needs to be other sources of funding,” he said.

A public private partnership to discover new antimalarials: the Medicines for Malaria Venture

Malaria affects “massive numbers”, said Professor Charman, but “until MMV [the Medicines for Malaria Venture] came along, there was little research going on”. The disease is also undergoing a resurgence and there is a “double whammy” of resistance — through the emergence of drug-resistant strains of parasite and insecticide-resistant strains of mosquitoes — to contend with.

Moreover, if we anticipate the changes that global warming will bring, malaria may not remain a disease of the developing world — places like southern Europe, California, Florida and northern Australia, could also host malaria, he warned.

Options to tackle the disease include drugs, vaccines (still estimated to be about 10 years away despite significant progress in the past couple of years) and bednets. Bednets are effective in preventing children from being bitten, but they are expensive — a couple of dollars. “But please don’t think these are the only answers: don’t forget the relationship between disease and poverty,” Professor Charman said.

Endemic areas often have limited medical health infrastructure, and issues of poverty and literacy. Treatments need to be simple, affordable and effective. Furthermore, with resistance developing so easily, there is a “dire need to undertake discovery and development in this area”.

In the 1990s, discussions led by the WHO and involving the International Federation of Pharmaceutical Manufacturers Association (IFPMA) concerned the lack of a co-ordinated malaria-related drug discovery programme. “What really got the attention of the group was the awareness [of the] future potential impact of malaria: all of a sudden, malaria was a first world disease. It shouldn’t require that to get people’s attention, but that did it,” he said.

This led to the MMV being set up with the mission of discovering, developing and delivering safe, effective and affordable antimalarials to treat and protect people most at risk.

The venture’s funding partners include the Gates Foundation, the Wellcome Trust, IFPMA, the Rockerfeller Foundation, MobilExxon, BHPBilliton, various governments and the World Bank. As a result, US$318m has been pledged through to 2010.

“It’s about involving people in an initiative where there is alignment between what both the corporate entity is after and the outcome for the organisation.”

The organisation has a corporate-style board and is well linked with government, industry and the global health community. There is also portfolio management of quality as there is in other corporate entities. Portfolio management is something that is rigorous within the venture because, at the end of the day, it will lead to success in terms of development, he said.

In the current portfolio of potential drugs, there are three products in phase 3 of development, including one in registration (Coartem D, developed in partnership with Novartis). “For a relatively young organisation to have collaboratively been able to contribute to having three products at that stage of development is terrific,” said Professor Charman.

The portfolio has drugs in preclinical phase and phase 1, but there is a gap in phase 2. “That gap is only going to be filled by having more and more discovery programmes. It’s about feeding the drug discovery engine with new targets, new chemistry, new biology in order to keep these new medicines coming through.

“We will always require medicines for malaria because the issue of drug resistance,” he said. The venture works with corporations, universities and research institutes throughout the world and, importantly, there are clinical trial sites in subsaharan Africa and south east Asia.

Artemisinin derivatives

A programme that Professor Charman is involved with is developing synthetic peroxide antimalarials based on artemisinin. The sweet wormwood plant, Artemesia annua, has been used as a Chinese herbal remedy since 340AD. The ravages of malaria in the Vietnam war, led to China beginning research in the early 1970s but the spread of knowledge was limited until the mid 1990s.

This plant is now grown throughout the world and artemisinin derivatives are a highly effective treatment option — the drugs are fast acting and, significantly, there is no evidence (yet) of resistance. However, monotherapy is not recommended (the treatment regimen is five to seven days so compliance becomes an issue).

The structure of the active component is complex but it has a unique peroxide pharmacophore. The drug works by producing free radicles which kill the parasite.

However, it has poor biopharmaceutic properties, including a short half-life, low and variable oral bioavailability and safety issues. In addition, being a natural product, supply (the plant takes 18 months to grow to maturity), purity and cost (US$600–800 per kg) are issues.

A design programme was, therefore, needed to come up with a synthetic peroxide that is orally active, has greater potency than semi-synthetic artemisinins, is effective with a three-day treatment regimen and, most importantly, costs no more than US$1 per treatment. An important factor is the ability to predict the daily dose because this allows a projection of costs in terms of treatment and dollars per kg, he explained.

Professor Charman said that peroxides have all sorts of issues associated with them — they are a challenge — but chemistry, lead optimisation and PKa can be used to design stable, effective and safe peroxide based compounds. The project brought together the University of Nebraska for the chemistry, the Swiss Tropical Institute for the biology, the Monash University for the absorption, distribution, metabolism, and excretion expertise and lead optimisation and Roche for its many years of experience and data.

However, “I’m a firm believer that academia, pharmaceutical scientists and especially pharmacists have significant roles to play in these sorts of programmes,” he added. He also noted that “working in a programme with different academic groups is about thinking differently” and that hard skills (technology) and soft skills (people/teams) are both important in terms of this partnership approach.

The programme produced a series of the synthetic peroxides and, after two years, has come up with a clinical candidate (OZ277), which is being developed by Ranbaxy Labs, India, and is now in Phase IIb clinical trials. A combination partner is also being assessed.

The MMV owns all the intellectual property. “That’s the only way it can occur. If there’s lots of people owning the IP, how are negotiations to be made,” Professor Charman said. With malaria, one of the key aspects is that there is no money to be made. Once you do not have the potential to make money, it is amazing what can be achieved, he said.


Reports from the 68th World Congress of Pharmacy and Pharmaceutical Sciences

Citation: The Pharmaceutical Journal URI: 10038059

Have your say

For commenting, please login or register as a user and agree to our Community Guidelines. You will be re-directed back to this page where you will have the ability to comment.

Recommended from Pharmaceutical Press

Search an extensive range of the world’s most trusted resources

Powered by MedicinesComplete
  • Print
  • Share
  • Comment
  • Save
  • Print Friendly Version of this pagePrint Get a PDF version of this webpagePDF

Supplementary images

  • 2008 World Congress of Pharmacy and Pharmaceutical Sciences

Newsletter Sign-up

Want to keep up with the latest news, comment and CPD articles in pharmacy and science? Subscribe to our free alerts.