While pharma companies make many medicines available to the developing world at cost – if not free – their research efforts are largely focused on diseases and conditions prevalent in countries that can afford to pay. Although one-sixth of the world’s population suffer from at least one neglected disease, between 1975 and 2004 just 18 of the 1556 new drugs launched treated them – 21 if you add tuberculosis.

Charities and academia very much lead the way in research into neglected diseases, with much of the money being spent coming from the Bill and Melinda Gates Foundation. Various agencies, such as the Medicines for Malaria Venture (MMV), the TB Alliance and the Drugs for Neglected Diseases Initiative (DNDi), have been set up to promote and coordinate research. DNDi, for example, was established in 2003 to coordinate and promote research into three related parasitic diseases: African trypanosomiasis, visceral leishmaniasis and Chagas disease. As its R&D director Simon Croft explains, the fundamental aim is to get academics, charities and industry to work together. ‘We know the pharmaceutical and biotechnology sectors aren’t committed to this area for a very simple reason – there are very few paying patients,’ he says. ‘The aim of public–private partnerships is to try and facilitate the interaction between academics and industry, and provide extra funding.’

DNDi and Croft have been working hard in the past two years to develop confidence within the pharma and biotech sectors. ‘They certainly have a role in terms of the chemistry but also, maybe, in terms of some of the drug development process. And this would not be at their cost, but through the funding of DNDi. What we need is their expertise – only industry really knows how to develop a drug, not academics. It’s a matter of getting teams of people from academia, from the disease-endemic countries and from industry to work together.’

One of the biggest problems comes right at the beginning of the process: lead identification. Charitable foundations are effective at funding clinical trials and access to medicines programmes, and are far better placed to coordinate clinical trials in the challenging locations, such as remote villages, where the diseases are endemic. But a molecule with good activity in the disease first has to be found, and optimised by medicinal chemists to make it more active, less likely to cause side-effects, and able to be assimilated by the human body. This is a hugely intensive and expensive process at which Big Pharma, with its libraries of millions of compounds and expertise in medicinal chemistry, is far better placed to succeed.

GlaxoSmithKline, for example, is building on its past success in malaria, and employs 50 scientists at a dedicated research site in Tres Cantos in Spain looking for drugs to treat malaria and tuberculosis. Novartis has gone one step further: it has established a research site within one of the disease-endemic countries, Singapore. The Novartis Institute for Tropical Diseases was set up as a PPP with the Singapore government’s economic development board four years ago, explains Paul Herrling, its director of corporate research.

‘We decided to allocate the same kind of technologies we would apply to, say, cancer and Alzheimer’s, to selected neglected diseases,’ he says. Initially set up to look for treatments for dengue and tuberculosis, in January this year a third project, in malaria, was started. NITD initially focused on two disease areas in order not to dilute its efforts, and as Novartis had just launched the antimalarial Coartem, it decided this was less of a priority. But the first signs of resistance to Coartem appearing in south-east Asia and the thinning out of MMV’s pipeline of candidates led to an offer from the Wellcome Trust and MMV to fully fund a malaria project.

NITD is fully integrated, including research in chemistry, genetics and molecular biology, and the plan is to identify leads and take them as far as the proof-of-concept in man stage. Further development will likely be carried out in partnership with other agencies, and any drugs would be made available at cost to the developing world. If all goes well, the first compounds could be in man by the end of 2008 for both TB and dengue.

‘The NITD is the world’s only drug discovery institute working on antiviral drugs for dengue, and there are very few looking at TB,’ Herrling says. ‘There is an increasing problem of resistant strains of TB, and we also want to shorten treatment times from the current six months. Even where the drugs still work, this is a very big hurdle.’

Perhaps the biggest advantage Big Pharma has is access to the millions of compounds in their libraries. ‘The agencies would like to have free access to our libraries for screening, but we cannot do this,’ Herrling says. ‘But as NITD is part of the wider Novartis research family, we can screen the libraries against neglected disease targets to find active compounds. So while we have 110 people working in Singapore, the overall resources are much bigger.’

Pfizer’s compound library is also being used to look for drugs to treat neglected diseases, but in a rather different way. It has made a collection of antiparasitic leads available to members of the screening network of WHO’s Special Programme for Research and Training in Tropical Diseases (TDR).

Mike Witty, group director at Pfizer coordinating the project, explains the real bottleneck is the discovery of new leads. ‘WHO [the World Health Organization] was sure they could get the funding and resources to develop new products if they had the candidates, but they were just not there,’ he says. ‘And their academic network had the expertise in antiparasitic screening, which we don’t have.’ Pfizer’s animal health division has done much research into antiparasitic agents, primarily for treating livestock, and it provided an initial 12 000 compounds from the library for screening.

‘They’ve now screened more than 10 000 compounds and we’re processing the information,’ he adds. ‘You get a lot more information when you look at that large number of compounds because you can look at patterns of activity and do some very interesting analysis, which WHO and the academics doing the screening just couldn’t do.’ As well as moving the best leads into in vivo testing, Pfizer is also going back to its file of three million compounds to look for similar compounds that might be more active.

DNDi’s Croft thinks the response thus far from the pharma sector has been very good. ‘Companies have said there’s a possibility for interaction,’ he claims. ‘Things are finally moving, and the next stage is to turn the discussions we’ve had into solid projects. We’ve already seen how GSK has built on its work with malaria and TB, and are using this as a very good piece of self-promotion.

‘Once the barriers between industry and academia are broken down, it will also help the funding situation, as governments and philanthropists will see the big players taking part. And as more funding becomes available, you can fund better links between the academic innovators, the pharmaceutical developers and the disease-endemic countries. It’s all part of a change which has occurred in the past six years, and organisations like DNDi and MMV are part of that. I’m not saying they’ll be part of it forever, but maybe in this interim period, perhaps the next 10 years, they have an important role to play in ensuring there is a flow of projects that offer the potential for new drugs to treat these neglected diseases.’

BOX: Learning by example

Both Novartis and Pfizer have an educational element within their collaborations. Paul Herrling says NITD is training scientists from developing countries to discover drugs for the diseases that affect their countries. It has just started a Masters course, with students being taught by the University of Basel, the Swiss Tropical Institute, the National University of Singapore and NITD. ‘It’s a unique course where they study in both Switzerland and Singapore,’ he says.

Meanwhile, Pfizer is training WHO-funded postdocs in its research labs in Sandwich, Kent, in the art of medicinal chemistry as part of WHO-TDR’s medicinal chemistry network. There are currently two on site: Chitalu Musonda, a Zambian who recently finished a PhD at the University of Cape Town, and Meenakshi Jain from India. Musonda explains he is working in four disease areas: malaria, trypanosomiasis, Chagas disease and leishmaniasis. ‘When Pfizer gets the results on its compounds back from the WHO screens, I choose the best and do medicinal chemistry with them to improve the leads,’ he says. ‘It’s been a great learning experience – I’ve only come across it in theory before, and it’s an opportunity to put it into practice.’

He’s been in the lab since last August, and is hoping to extend his stay by a further year. ‘After two years I’ll have learnt more than I did during my PhD,’ he adds. ‘I’m loving every bit of it, and I’m very confident I’ll be able to teach others when I get back to South Africa.’