A decade of discovery for malaria medicines
Dr Margaret Chan
Director-General of the World Health Organization
Baroness Chalker, Dr Hentschel, Distinguished Board Members, distinguished scientists, partners and donors, ladies and gentlemen,
I am delighted to speak to you as you commemorate the 10th anniversary of the Medicines for Malaria Venture. Before its birth, WHO and TDR played the role of a midwife in a gestation period of discussions and negotiations that took more than two years. We are proud of the result.
Let me congratulate you on your big birthday present, the recent multi-million dollar grant announced by the Bill and Melinda Gates Foundation. At a time of global economic downturn, this is an expression of respect for the significance of your achievements, and of confidence in your mission and business plan for the future.
Good work sustains momentum, even in difficult times. Achievements earn support, even in difficult times, especially when the need is so great and the effort so daring.
The world is in a mess, with an economic recession on one hand, a changing climate on the other, and an influenza pandemic spreading everywhere. But the desire to seek greater fairness in distributing the benefits of medical and scientific progress remains steadfast.
Public health has long struggled to ensure that people do not die needlessly for want of access to existing interventions. MMV has had a higher ambition. People should not die for want of incentives to develop new products for diseases that almost exclusively affect the poor.
This ambition becomes all the more important for a disease like malaria that has rapidly developed resistance to one class of antimalarial compounds after another. Already we are hearing the rumblings of artemisinin resistance and the big storm that is likely to follow. We must stay ahead of the parasite. This need, and your unique approach to meeting this need, have been soundly endorsed.
On this occasion, we are celebrating the power of innovation. We are celebrating the courage to do something conventional like drug discovery in a radically different way. We are celebrating what can be achieved when the unmet health needs of the poor become a legitimate and compelling incentive for drug discovery.
From its outset, MMV has been a hard-nosed business venture with a compassionate, humanitarian heart. You have demonstrated a smart use of market forces and competition to stimulate drug discovery for a market that has little commercial appeal. And you have demonstrated the power unleashed by a well-conceived, well-managed, and forward-looking partnership.
From its inception, MMV has been different in ground-breaking ways. For a long time, efforts to discover new drugs for diseases of the poor were opportunistic in nature. They screened existing compounds, often licensed for veterinary use, hoping to discover activity against a human infective agent.
This opportunistic approach brought us ivermectin for river blindness, and later for lymphatic filariasis as well. It also ushered in an era of generous industry donations to fill the vacuum that occurs when a new product becomes available, those in need number in the millions, and yet this huge market has no purchasing power.
Industry donations, in turn, led to the strategy of mass preventive chemotherapy and a vastly simplified operational approach for combating several overlapping diseases together. Success increased the momentum, and the elimination of several ancient and debilitating tropical diseases is now in sight for 2015.
In this case, an opportunistic approach to drug discovery eventually inspired generosity, permitted a massive extension of coverage, and supported ambitious goals
MMV’s creation marked a radical change. It pioneered a strategic approach to drug development. This was a new model that defined the profile of an ideal product and set out to develop this ideal in a streamlined, expedited, and cost-effective way.
MMV pioneered a way to bring badly needed yet unprofitable drugs to market using the same sophisticated technologies and quality standards that characterize industry-run discovery projects for commercially attractive diseases. This was an exercise in what can happen when extremely poor people are regarded as a legitimate market, with the same dynamics of demand and supply, only missing an ability to pay as part of the equation.
Since the beginning, MMV has been lean, competitive, and flexible, selecting and funding promising projects to meet a strategic outcome. High ambitions and a strong sense of purpose were present at the start, as was the need for generous financial support. And the need was pressing.
As they say, necessity is the mother of invention. In the 1990s, observers of the malaria situation could offer a single positive assessment. The malaria situation is stable, they said. It could hardly get any worse.
At the time, malaria-related deaths in Africa had risen from 18% of total child mortality prior to 1960, to an unprecedented 30% of total child mortality, accounting for 1 in 3 childhood deaths in Africa. With the parasite rapidly developing resistance to first-line antimalarials, it is safe to say that Africa, at least, was on the verge of a humanitarian crisis.
The creation of MMV departed from a deadly impasse: the inevitability of drug resistance and the lack of market incentives to stimulate the development of replacement products. This was the first deliberate and carefully calculated move to stay ahead of a parasite. And let me thank your donors and partners for their wisdom in seeing this reality and embracing this opportunity.
Can we allow a mass killer like malaria to evolve to the point where we have nothing in hand to treat or cure it? What would this say about the state of our world? If our actions and decisions have any kind of moral or ethical dimension, how could we let millions of people, mostly young children, die because of a failure, basically, of the market?
I believe these were some of the issues at stake when the Medicines for Malaria Venture launched its discovery mission 10 years ago.
Efforts to improve the malaria situation can be justified on many counts. They can be justified in economic terms. Each year, Africa loses an estimated $12 billion due to malaria in direct and indirect costs. Malaria control can be justified as a pro-poor strategy, since malaria takes its heaviest toll on the poorest of the poor, and saps their productivity. Efforts can be justified as a women’s issue, or a child survival issue, or a pro-Africa issue, or part of the drive to reach the Millennium Development Goals.
But I personally believe the most potent justification centres on the basic value of fairness. People should not be denied access to life-saving medicines for unfair reasons, including those with economic causes.
Innovation is often met with scepticism. As we all know, malaria is a stubborn disease that has soundly defeated the international community in the past. At the beginning, there were some questions about whether this new venture could work. Could it really be competitive? Would the inevitable collaboration with Big Pharma compromise integrity?
Could MMV discover new products and bring them to market? Could it do so fast enough? After all, drug discovery is a notoriously high-risk and time-consuming undertaking fraught with uncertainty. Was it wise to rely on a new partnership model, with untested operational features? What if partners lose patience and funds dry up?
At the same time, many others hoped that the Venture’s unique partnership model, including the sharing of risks and assets, could reduce substantially the cost of developing a new product through to registration.
Ten years later, let me congratulate MMV for its robust and diverse portfolio, with more than 50 projects in your pipeline of discovery, preclinical, and clinical development. You have done so at a cost well below estimates for commercial production.
Let me congratulate you on last year’s licensing, by a stringent regulatory authority, of Coartem Dispersible, developed in collaboration with Novartis. This is the first fixed-dose ACT formulated, packaged, and flavoured for paediatric use. I am personally fascinated by the field trials undertaken in African children that made a cherry flavour the evidence-based definition of delicious. This is genuinely important when the profile of a successful product includes its acceptability in the target population.
I know that you are expecting regulatory approval next year for an additional product, and that yet another one will be ready for submission to regulatory authorities, also next year.
The sceptics are quiet now, and with your new business plan that embraces the prospect of malaria eradication, the future looks bright.
Ladies and gentlemen,
How has the broader landscape of public health evolved during your first decade of discovery, and how might these changes affect your work in the future?
In just the past few years, the political and public profile of malaria has risen to unprecedented heights. Efforts to combat this disease, on multiple fronts, have been rewarded with their billion dollar moment. The significance of the MMV contribution has been soundly endorsed. The statistics in endemic countries are looking better and better. And eradication is back in the vocabulary.
I know that your new business plan has been broadened to accommodate the eradication goal. I know that you are casting the R&D net wider to include a quest for new compounds that can help interrupt transmission. Again, a strong sense of purpose and solid achievements mean that ambitions can be set even higher.
But let me point to three situations in which forces with a global sweep, placed against the reality of conditions in countries, have created some tensions and special challenges for public health.
First, one of the consequences of living in a closely interdependent and interconnected world is the fact that more and more crises have a global impact. A mistake made in one country or in one policy sphere rapidly spreads throughout the international systems that tie us all together.
Mistakes are contagious, but the consequences are not evenly felt. Developing countries have the greatest vulnerability and the least resilience. They are hit the hardest and take the longest to recover.
Despite all the promises, globalization has not turned out to be the rising ride that lifts all boats. Differences, within and between countries, in income levels, in opportunities, and in health outcomes, are greater today than at any time in recent history. This is a bitter irony in the midst of the most ambitious drive in history to reduce poverty and reduce the great gaps in health outcomes.
This makes work to combat the diseases of poverty all the more urgent. This makes every bit of progress all the more important. Healthier people mean greater resilience when the next global crisis inevitably strikes.
Second, the need to strengthen health systems is more widely appreciated than it was a decade ago. Ironically, this need became highly visible as progress towards the health-related Millennium Development Goals stalled. Simply stated, powerful interventions and the money to buy them will not produce better health outcomes in the absence of well-functioning systems for access and delivery.
At the same time, the Millennium Development Goals are a results-based, time-limited agenda. Donors are impatient and want tangible results, yet the strengthening of fundamental capacities takes time and is difficult to measure. This is another dilemma that we must face.
The third area I want to mention is perhaps the most challenging. Increasingly, public health is on the receiving end of bad or short-sighted policies made in other sectors. Public health had no say in the policies that created the financial crisis or made climate change inevitable, but public health bears the brunt of the consequences.
Time and time again, health is a peripheral issue when the policies that shape this world are set. When health policies clash with prospects for economic gain, economic interests trump health concerns time and time again. Time and time again, health bears the brunt of short-sighted, narrowly focused policies made in other sectors.
Money makes the world go round, and this will never change. But there are some smart ways to deal with this reality.
For its part, WHO and its Member States have just completed some years of negotiations to work out international consensus on the issues of public health, innovation, and intellectual property. With the adoption this May, by consensus, of a resolution on this matter, we have broken new ground. Ways can indeed be found to make the process of drug discovery and development needs-driven as well as profit-driven. International agreements that govern the global trading system can indeed by shaped in ways that favour health.
I believe the Medicines for Malaria Venture, which was needs-driven from the start, offers some further examples, especially in your more recent work on access and delivery. Your mission of reducing deaths from malaria brings you face-to-face with these issues. Even the best product does no good if it fails to reach those in need.
Furthermore, irrational prescribing can shorten the lifespan of the products you bring to market, and thus reduce the return on your investment. Your work in this area, including initiatives to gather market intelligence, has already yielded a new understanding of barriers to access in different African settings.
Price governs the choices of the poor. This is the reality of the market for malaria medicines. When health services in the public sector are weak, people will obtain drugs wherever they can find them. As studies show, available drugs are often monotherapies, or they are ineffective, of substandard quality, or fake. Again, this is a function of weak health systems, weak or non-existent regulatory capacity, and poverty.
As a result, the treatment of malaria is a largely uncontrolled and unregulated over-the-counter hit-or-miss mess.
For me, one of the most encouraging trends in public health is the power of commitment to unleash the best of human ingenuity. I admire the Affordable Medicines Facility for Malaria initiative as a brilliant innovation. This is the kind of hard-nosed pragmatism that gets results in public health. It looks at the reality of conditions in the developing world, identifies the forces that shape the reality, and then outsmarts them.
If price affects access, make the price of the best products competitive, and thus drive ineffective, substandard or counterfeit products off the market.
Ladies and gentlemen,
Let me conclude with a personal observation. Since taking office in early 2007, one of the most rewarding experiences for me has come during visits to endemic African countries, where I have seen the empty beds in the malaria wards and heard the personal joy of doctors, nurses, and mothers.
These experiences mean more to me than the statistics, though the statistics, too, give cause for optimism. Finally, the efforts of ministries of health, R&D, multiple initiatives, and multiple partners are beginning to turn this disease around.
The benefits are likewise multiple, and sometimes unexpected. In some African countries, the availability of rapid diagnostic tests for malaria is contributing to a more rational use of antimalarials, but also to better detection of pneumonia, with the result that childhood deaths from pneumonia are also going down.
This is a fascinating and exciting time to be working on malaria, but also still a very challenging time. Constant evolution and adaptation are the survival mechanisms of the microbial and parasitic worlds. With your proven track record and bright future, we will be counting on the Medicines for Malaria Venture to help us outsmart and outmanoeuvre a parasite that still causes so much suffering and takes so many lives.
May its days be numbered!