Geneva based Medicines for Malaria Venture (MMV) recently gained worldwide attention when the Bill and Melinda Gates Foundation awarded them an additional$40 million grant to develop new anti-malarial drugs. One of the key projects that the Gates Foundation and MMV have identified as an "accelerated" project for development is the Synthetic Peroxide project. This project already captured the front page of Wall Street Journal last summer when MMV and Ranbaxy Laboratories Limited announced the forming of their innovative partnership to develop this anti-malarial drug. The Ranbaxy-MMV agreement is seen as a major achievement for the non-profit foundation. MMV's objective is to register at least one new drug every five years beginning no later than 2010.

Dr Dame Bridget Ogilvie, Chair, Medicines for Malaria Venture (MMV) spoke to Joe C Mathew of Pharmabiz.com about MMV's projects and plans.

Dr Ogilvie, a trustee of Cancer Research UK, is the Chairman of the Lister Institute for Preventive Medicine and has a range of responsibilities in the medical science sector including membership on the AstraZeneca board. She is also Chair of the Association of Medical Research Charities (UK). A Fellow of the Royal Society, she is currently a Visiting Professor at the University College London, she was formerly Director of the Wellcome Trust (1991-98). Excerpts:

MMV is in its fourth year of existence. What has it achieved so far?

MMV has pioneered the concept of public-private partnership and networking at an international level for research in developing drugs specifically needed to counter diseases in developing countries. Most similar attempts, for instance the Drugs for Neglected Diseases initiative (DNDi), founded by an international partnership of seven eminent public and private institutions, FIND etc, have derived some of their vision inspiration regarding operational performance of MMV.

MMV was designated by WHO as "the premier public-private partnership for developing new malaria drugs."

We are also very happy that our efforts are being recognized in malaria's heartland, Sub-Saharan Africa. In this context I am delighted to welcome His Excellency Dr. Pascoal Mocumbi, the Prime Minister of Mozambique to our Board. His first-hand knowledge of the devastating effects of malaria and commitment to public health in Africa and the world will help galvanize the support of the developing and developed countries in the search for the much needed medicines.

Not everything has of course been straightforward. The past year has been a period of consolidation and re-examination of a number of important issues for us. We feel that after three years we are no longer an experiment that needs to be carefully monitored and analysed but rather have demonstrated, through clear results, the essential validity of our R&D model. We have exceeded most expectations and want to move forward rapidly on the momentum we have created.

Why do you say that the past year was that of consolidation and re-examination?

One compelling reason for this arose from the very success that MMV was achieving. In building up and advancing our R&D portfolio we saw a growing need for a clearer roadmap for how drugs resulting from our portfolio would eventually be delivered to help reduce the global malaria burden, a roadmap that had not been attempted in the 1999 plan. That is why we felt that we needed an update of our business plan after three years of functioning.

What is your new business plan?

The reality expressed in the business plan is that both the R&D value-chain to registration, and particularly issues related to the subsequent drug delivery pathways, are very complex and can be both multifaceted and intimidating to the uninitiated. It would be foolish to pretend that all issues have been fully addressed through the updating of the business plan - but many important points have been clarified or exposed for further analysis.

The updated plan in particular recognizes that there are many global and local players involved with malaria R&D and control, and that it is incumbent on us to coordinate and synergize with their activities. Only by doing this we can achieve the quickest possible impact of the drugs arising from our R&D activities on the current unacceptably high, and in Africa perhaps growing, disease burden due to malaria.

What are your plans for the Gates grant?

We are deeply gratified by this additional grant. It is another testament that we are on the right track. The investment of $40 million from the Gates Foundation comes at a crucial juncture in our mission to find new drugs for malaria - as we increasingly move from drug discovery to drug development. Several of our projects are or are about to enter into to costly clinical trials phase, and more are scheduled over the next few years.

Development of drugs is as you know hugely expensive. The Gates grant provides an enormous boost to MMV's R&D funding but does not fund our total needs. We are trying very hard to find additional funding from governments of developed countries. Governments need to rearrange their priorities and make available appropriate funding to support R&D in malaria. They need to follow the lead of the private foundations and step up to the challenge of rolling back malaria.

The money from the Gates grant will be used to fund research for our 21 projects in the portfolio with an emphasis on a few accelerated projects such as OZ (Synthetic Peroxide). Ranbaxy, our pharma-partner, is working hard with us to develop a potent, low-cost synthetic drug. The drug is potentially an affordable alternative to the most effective class of anti-malarial drugs available today - artemisinins - which are too costly to reach the millions who need them. We hope to move a candidate drug into Phase I human trials by mid-2004.

What are some other recent developments in malaria research?

One of the most notable events in malaria research was the publication of the malaria genome sequence. The malaria parasite is one of the first organisms to have its genome fully sequenced and the information has already acted as a spur to research, with new drugs and potential drug targets being identified and more understanding about drug resistance emerging. Other genetic studies in 2002 showed us that the malaria parasite has been evolving for much longer than we thought and has accumulated many mutations, perhaps accounting for the fact that resistant strains appear quite readily. For instance, resistance to chloroquine, the cheapest and most widely available antimalarial, is thought likely to have evolved separately at least four times in different parts of the world.

Recommendations on how to use the latest genetic advances to develop new drugs, vaccines and other tools for the control of malaria emerged from the Third MIM (Multilateral Initiative on Malaria) Pan-African Malaria Conference held in Tanzania in November 2002.

Another sign of increasing global awareness about malaria was perhaps seen when the World Congress of Pharmacology, at its XIVth session in July, held a symposium on new approaches to the treatment of malaria. This was the first focus on malaria at the congress for a long time. But these advances in malaria research have yet to be translated into successful malaria control.

What are the challenges before Malaria control programmes?

The biggest challenge facing malaria control today is seen to be drug resistance. In sub- Saharan Africa, where the most deadly form of malaria is common, resistance to chloroquine has become widespread and resistance to sulfadoxine-pyrimethamine (SP), often used as the first and least expensive alternative to chloroquine, is increasing. Thus many countries have to turn to more expensive drugs. These countries may already be spending 40% of their public health expenditure on malaria.

Extreme poverty is another issue which undermines malaria control. Today, malaria is recognized as being both a cause and a result of poverty, and a major constraint to economic development. There are substantial differences in GDP between countries with and without malaria, and it has been estimated that the disease costs Africa more than USD 12 billion every year in lost GDP.

Also undermining malaria control is the partial collapse of some African health services under the impact of HIV.

So in 2003, as in many previous years, at least one million people, mostly children under the age of five, died from malaria. Many children continued to suffer cognitive, learning and behavioral damage due to repeated malaria infection. Many countries and communities continued to suffer enormous economic and social burdens inflicted by malaria.

Actually, the major obstacle facing malaria is the lack of funds. Currently malaria funding is grossly under-resourced. Spending on malaria control is estimated at $200 million annually - about 10% of the $2 billion estimated to be needed by macroeconomists.

What is the present status of MMV-led R&D in malarial drugs?

MMV now manages the largest portfolio of malaria drug research in history with 21 projects in different development stages. The clinical development projects are gaining momentum and the majority of preclinical projects are set to move into clinical studies in 2004. There are now four discovery projects, following the addition of the dihydrofolate reductase project and the advancement of the synthetic peroxide project to clinical development. Among the exploratory projects, the dihydrofolate reductase project has met its goals and is moving to a full discovery project. On the other hand, as is normal with R&D some projects have failed to meet their goals and have been terminated.

In addition to new drugs we are we are also going to collaborate with Novartis on a product extension - a pediatric formulation of CoartemR (Artemether and Lumefrantrine). This could be used as a first line treatment for infants suffering from acute, uncomplicated plasmodium Falciparum malaria.