"In MSF, people come and go. Some do one field assignment. Others – like me - are involved with the organization for much longer. Regardless how long we've worked for this organization, our experience stays in us forever and changes our vision of humanity."

-Sophie Delaunay, ​MSF-USA Executive Director 

November 16, 2013

Introduction

My life with MSF started in the early nineties in Thailand. MSF was providing medical care in Burmese refugee camps along the Thai-Burmese border. Malaria was the main cause of morbidity and mortality among this population. It was resistant to most of the available drugs to the point that young children and pregnant woman had become untreatable. The MSF team was frustrated with this situation—they documented the resistances and looked for alternatives without finding a solution.

Then some patients came to us with a Chinese drug smuggled into Thailand through Burma. This drug was based on artemisinin derivatives. This family of new drugs was poorly known outside China. In fact, during the Vietnam War, for both the US and the Vietnamese forces, malaria was a real burden, keeping large numbers of soldiers out of combat. The Vietnamese asked their Chinese ally to provide them with better treatments. Chinese academics first screened the plants used in their traditional medicine. This is how the artemisinin derivatives were re-discovered. Meanwhile, Western laboratories, especially the US military research institutions, identified several new molecules, among them mefloquine and halofantrine.

The Vietnam War was over before this new generation of drugs had any impact on the treatment of military forces. Nonetheless, the two US drugs were developed and we used them in our programs. Later on, the parasite, Plasmodium falciparum, rapidly developed resistance against mefloquine and halofantrine. This is where the story starts for us and when we turned to the Chinese version.

With the Chinese drugs, three main difficulties immediately emerged: first of all, these drugs had not been studied according to international scientific standards; secondly, they were not economically attractive for big PHARMA to invest in because malaria was a disease of the poor, and also because the initial products were not patentable by Western pharmaceutical companies under the Chinese law at the time. And thirdly, politically, even psychologically, it was difficult for Western institutions to recognize that Chinese medical institutions had won the medical battle and found an alternative to outdated malaria drugs.

The first step out of this deadlock was to carry out clinical trials using alternative treatments. This was absolutely necessary if we were to have a chance at developing an effective treatment for one of the world’s most common and deadly diseases before it became completely untreatable. Looking at epidemiological data, it was obvious that there was a crucial need for a new treatment for malaria in other parts of the world, too. At the end of the nineties, the situation was rapidly worsening in sub-Saharan Africa. So between 1996 and 2004, MSF enrolled 12,000 patients in 43 clinical trials in 18 countries. Our efficacy studies were conducted according to scientific standards and published in peer-reviewed journals, and provided evidence on the efficacy of most drug regimens containing artesunate. We also supported the founding of the Drugs for Neglected Diseases initiative (DNDi) in 2003, whose mission was to fast track the development of drugs for neglected diseases. In addition to assisting in the development of new regimens to treat sleeping sickness, visceral leishmaniasis, and Chagas disease, DNDi helped create ASAQ and ASMQ, two single-dose combination treatments for malaria that include artemisinin and that are in widespread use in Africa and Asia today.

Artemisinin-based treatments are now part of WHO recommended protocols and have become a reference therapeutic option for malaria everywhere in the world. But as we speak, our teams in Cambodia are seeing the first signs of resistance to this treatment. We are already certain that this resistance will continue to spread and we can even anticipate which route it’ll take. But there is no single alternative treatment in sight.

The reason I shared this story on malaria with you is that in my view it is emblematic of a number of challenges that we still face today in our medical interventions: first, the lack of needs-driven innovation and research, especially when patients are poor and neglected; second, the persistence of numerous barriers (mostly economic) to access; and third, the need to fundamentally change the system in the long-run to promote innovation and access.

In my talk today, I will focus primarily on TB, vaccines, and hepatitis C, three areas where innovation and access gaps in the response from the global health system are currently causing tremendous suffering among the patients we serve. These are going to be three key priorities for MSF in the coming years. The fight for access to medicines by MSF always originates from a very concrete and practical problem faced by patients. It is not a moral or intellectual campaign that we embrace simply because we think it is the right cause.

Lack of a Needs-Driven R&D System

Let’s start with the lack of a needs-driven R&D system: Most of the time, our difficulty to treat patients will come from a lack of appropriate treatment, vaccine, or diagnostic tool, and a lack of attention to groups that are particularly vulnerable. We all know the old estimate that less than 10% of research is committed to diseases and conditions that account for 90% of the global disease burden. Last year, we organized an innovation conference in New York with DNDi and Mount Sinai. We decided to look at the numbers again. The resulting study, which was published in the Lancet just a few weeks ago, shows that, despite some progress, between 2000 and 2011 only 3.4% of all new drug approvals were indicated for neglected diseases. Meanwhile the global burden of disease is estimated at 11%. It is worth pointing out that of these products, only 4 (or 1%) were truly new chemical entities, 3 of which were approved for malaria, and no new drugs for TB or neglected tropical diseases were approved over the decade. Most newly developed therapeutic products were repurposed versions of existing drugs. Our conclusion is simple: the system is broken and a "fatal imbalance" remains in R&D for many neglected patients.

Take vaccines and TB for example: Vaccines have long been part of the services MSF offers, particularly in countries where vaccine coverage is low. As part of basic health care programs in these places, teams provide children with a slate of vaccines currently recommended by the World Health Organization: DTP (diphtheria, tetanus, pertussis), hepatitis B, Haemophilius influenzae type b (Hib), BCG (against tuberculosis), measles, polio, and, increasingly, pneumococcal conjugate vaccine.

According to WHO estimates, globally in 2012 more than 22 million children did not benefit from basic vaccination. One big barrier to better coverage is that in rural areas of resource-limited settings, parents have to travel far to get their children vaccinated, simply because in many cases, it’s not possible to bring the vaccines to them. At present, these vaccines have storage and delivery requirements that can be very difficult to uphold in resource-limited settings. Imagine trying to reach children in a remote village in, say, India, or Chad, or Central African Republic. The roads are bad and prone to flooding during the rainy season. The vaccines themselves need to be kept at a certain temperature—between 2° to 8° Celsius, or roughly 35° to 46° Fahrenheit—lest they become ineffective, but there’s no electricity along much of the route. And most vaccines have to be administered with needles by trained health professionals, who are often in short supply in countries lagging in terms of development or afflicted by years of conflict. MSF teams must contend with all of these challenges, from the logistics of the cold chains, to the provision of trained medical staff. There is a profound need for vaccines that are better-adapted to the settings in which they will be used. If they could withstand higher temperatures, if they could be delivered through a mist or a patch, or if the course could be completed with fewer doses, it would be far more feasible to get the vaccines and health workers to the most decentralized health facilities, closer to where most people live. Rather than sticking with a one-size-fits-all approach—that is usually based on US and European models—vaccines R&D efforts should be much more global, responding to the needs of all children and the health systems that try to reach them.

Moving on to tuberculosis: After more than 4 decades of inaction, as we speak, two new promising drugs for TB are coming to market, but very little effort has been made by their producers to assess the drugs’ efficacy in new combination treatments or in sharing clinical safety data that would allow others to do this work. Effective TB treatment requires a robust combination of different classes of drugs to prevent development of resistance to individual drugs. So, even though the advent of new promising TB drugs is a milestone for us and for the 30,000 TB patients we treat in a year, these new drugs won’t actually do much to curb the drug-resistant TB epidemic until we know how to combine them and what kind of regimen is appropriate for treatment, and results from the necessary clinical trials are still many years away. Furthermore, producers have little incentive to make these new drugs affordable for all those who, from South Africa to Uzbekistan, are currently dying from drug-resistant TB and who desperately need access to new and better treatment regimens. So, as with malaria 20 years ago, big pharma lacks any incentive to perform the research necessary to meet patient needs. Companies are incentivized to work in silos to bring individual drugs to market, rather than to perform the collaborative research needed to develop and bring new regimens to market. We face a future where eventually treatment providers and NGOs will have to step up and conduct clinical trials themselves as we had to in malaria.

And that is why we need a fundamental change in the way in which medical research and development is conducted, and this is what MSF, UAEM, and many others are trying to enact through the WHO. As part of the implementation of the 2008 WHO Global Strategy and Plan of Action on Public Health, Innovation, and Intellectual Property and some of the recommendations included in the 2012 report by the Consultative Expert Working Group on Research and Development: Financing and Coordination (the CEWG Report), MSF has submitted two proposals for demonstration projects on innovative incentive and funding mechanisms for R&D: one for open-source, multiplex, affordable fever diagnostics and another for a new framework for TB regimen development.

Allow me to briefly explain our TB proposal, called the 3P Project (Push, Pull, Pool). We are proposing the creation of an open, collaborative framework for TB drug regimen development based on the sharing of data, the pooling of intellectual property, and the creation of incentives in the form of prizes and grants. Our proposal encourages multiple actors to enter the R&D process in order to accelerate development timelines, improve R&D effectiveness, and provide more equitable access to better medicines. The proposal de-links the costs of research and development from the prices of the end products created (known as “delinkage”) and embraces open, collaborative innovation models.

Your help in supporting our efforts to explain the CEWG process and the MSF proposals (as well as other proposals) to academics, researchers, universities, and many others would be extremely valuable. We need to broaden the discussion beyond the corridors of Geneva.

MSF has also launched an online TB manifesto advocating for better treatments that I encourage you all to sign and share broadly.

Access Barriers

My second point relates to the newer access barriers we face. We know too well that access to medicine is not just a matter of finding the right drug or adapting tools to the contexts in which they’ll be deployed, it is about making them accessible and affordable to those who need them most. The countries where MSF intervenes today present a very different epidemiologic profile than in the past decade, from Pakistan to DRC, and from Syria to Kenya. We no longer have to deal only with a few rare tropical diseases, or only the poorest countries. Many of the most difficult access challenges are going to be in developing countries that are classified as middle-income economies. And apart from having to ensure access to diagnostics and treatments for the big three - HIV, TB and malaria, as in the US and Europe, non-communicable diseases, or NCDs, such as cancer, hypertension, diabetes, and cardiovascular diseases are more and more common and widespread among the populations we are serving. Existing alternatives for us and for the countries where we work are limited to treatments and tools that are most of the time outrageously expensive. MSF is joining late in the game of NCDs. Although we are of course treating patients affected with some NCDs, we have not yet fully adapted our emergency set up to these pathologies, nor have we properly documented the state of affairs, which would allow us to engage in a more aggressive campaign. This is a work in process.

In other areas however, challenges of access and affordability are quite obvious. After more than 40 years with no new drugs, the newly FDA-approved TB treatment bedaquiline will most likely cost around 900 USD for a 6-month treatment course in least developed countries, and 3,000 USD for a six-month course in middle income countries. That’s for just one drug, but several drugs are needed for effective TB treatment. This means that new treatment combinations will still cost in excess of several thousand dollars per patient even in the poorest countries, as they do today , and potentially much more in countries classified as ‘middle-income,’ of which many have a high burden of TB, such as India, Ukraine and Uzbekistan.

At least 185 million people worldwide have been infected with hepatitis C virus (HCV), but access to treatment is and will continue to be a huge challenge. The current treatment peginterferon is expensive and not ideal in terms of medical outcomes, but some very promising new hepatitis C oral treatments are coming out of the pipeline very soon. The problem is that they are going to be completely unaffordable for many. Let me give you one example: sofubsuvir from Gilead is going to receive FDA and European regulatory approval very soon. According to the latest estimates, it could be priced in the range of 50-80,000 USD for a treatment course in wealthy countries. And there is yet no public indication on what Gilead will charge for its use in developing countries. We know that competition, if allowed, could be a game changer because the cost of manufacturing has been estimated to be around 200 USD per treatment.

Bringing prices of vaccines down is another crucial priority. In 2001, the cost to provide a child with basic vaccinations was $1.38. Today, it’s $38.80, an increase of more than 2,700 percent. Given the fact that the number of basic antigens recommended by the WHO has climbed from 6 to 11, the price was certain to rise. But the jump is largely attributable to the high price of new vaccines—particularly those for rotavirus and pneumococcal disease, which together make up more than 70 percent of the price tag—resulting in a cost structure that is simply not sustainable for many countries. GAVI has committed almost $8 billion dollars to introduce new vaccines and strengthen existing immunization systems in the developing world, and as the largest purchaser of vaccines for poorer countries, the organization can negotiate more favorable terms for countries it covers. But once a country’s annual per capita income rises above $1,550, that country begins to “graduate” and move out from under the GAVI umbrella, into terrain where they’ll be forced to pay incrementally more in the years that follow until they pay the full GAVI price, ultimately followed by paying full market prices. By 2016, for instance, some 17 countries will have lost GAVI support, and more countries are starting the “graduation” process each year. No longer eligible for reduced prices, countries like Republic of Congo and Honduras may soon have to choose which of the vaccines they can afford and which ones their youngest citizens will have to go without. One step to correct this would be to loosen the stranglehold a handful of pharmaceutical companies have over the vaccine market, allowing greater competition that would drive down costs. Another step would be for GAVI to use its purchasing power to negotiate better prices, and, just as importantly, give organizations like MSF—organizations that are on the ground, ready to put in the effort to reach as many children as possible—access to vaccines at the prices they negotiate for governments. These various issues came together in South Sudan’s Yida refugee camp this past year. A huge influx of refugees from Sudan had overwhelmed the services on the ground and created a dismal environment in which disease could easily spread. MSF teams built medical facilities, saw tens of thousands of patients, and provided a wide range of urgently needed services. MSF also identified pneumococcal diseases as one of the main reasons children were dying in the camp and decided to pursue vaccinating children with the pneumococcal vaccine, as well as the pentavalent vaccine. These vaccines were not yet in South Sudan’s national immunization schedule, though, so MSF had to purchase them ourselves. But because GAVI does not make its prices available to nongovernmental organizations and humanitarian actors such as MSF, it took 11 months of lengthy negotiations and bureaucratic hurdles for MSF to secure access to the pneumococcal vaccine. MSF was finally able to obtain a limited number of doses of the vaccine directly from one of the manufacturers and began vaccinating children in the camp in July of this year. This experience points to the fact that a more workable solution is needed to allow humanitarian actors to respond quickly when needs arise. We know it is possible. Two years ago, for instance, the Serum Institute, together with partners like PATH launched a new meningitis vaccine called MenAfriVac, which protects children from a strain of meningitis (meningitis A) prominent in Africa’s so-called meningitis belt. Because the vaccine was developed to serve people, not profits, it is sold at an extremely reasonable price, just 50 cents per dose. MenAfriVac is an example of an innovation model implementing delinkage. Even better, MenAfriVac’s protection lasted longer than the vaccine that was previously in use. Its widespread rollout in the region has already led to a significant decrease in the number of meningitis outbreaks.

There is quite a fair amount of public investment going to vaccines, TB and hepatitis. If the research agendas of public institutions and universities could be positively influenced to better respond to the needs of patients, many things could change. We need your voice and your activism in actively calling on governments, donors and universities to focus research on real public health needs and gaps, and to include access and affordability strategies from the beginning of the R&D process, with for example, the implementation of delinkage and the use of humanitarian and equitable pricing and technology licensing strategies.

The need for a new system

Let me now raise my third and last point: the malaria story illustrates how history repeats itself over and over again. Most of the time with the same cynicism and equally tragic consequences for the patients. Today, with the emerging resistance to artemisinin, we are back to square one. As the film’s narrator pointed out in the recently released documentary, Fire in the Blood: the drug companies have lost some of the battles for access, but they certainly haven’t lost the war.

Indeed we've won a few battles in the fight for access to medicines: we’ve secured price reductions of first line ARVs, whose prices have dropped by 99% in the last 10 years, and increased treatment access scale up to nearly 10 million people today. The Doha Declaration in 2001 was a turning point in the fight for access when it placed public health ahead of commercial interests. From 2002 to 2010, official development assistance committed to health more than quadrupled, from 4.4 billion USD in 2002 to 18.4 billion USD in 2010, with the US government contributing a third of it.

We all remember in 2001 the victory by the South African government over 39 drug companies attempting to block legislation that made medicine more affordable for the country. More recently, the Indian Supreme Court denial of a patent to Novartis drug Gleevec marked their affirmation to protect the availability of cheap generic drugs for poor patients and the right that governments have to fight patent evergreening.

These were important milestones, but we haven’t won the war. We've made tremendous progress in understanding how the current system functions and where it fails, but we haven't fixed it. And as the current system evolves we are faced with emerging challenges and persistent questions.

How can we align economic interests and public health imperatives, especially for underserved populations? As my colleague Judit Rius Sanjuan presented this morning, we are closely following the CEWG process, which we think could offer some opportunities of reforming the current model of innovation and research

How can we allow science to work in a truly open, collaborative fashion, serving public health needs? How can we make new science more affordable? We know how generic competition worked to lower prices for HIV drugs, but can those lessons be applied to other diseases and new technologies, and particularly biological products?

UAEM can be instrumental in proposing and forcing solutions to these problems, as we’ve seen with UAEM’s stavudine campaign and continued commitment to holding universities accountable through initiatives like the UAEM report cards and numerous statements of principle sign-ons. You are well equipped to reach out to researchers, academics and other stakeholders who are key in this dialogue. You will be the practitioner, witnessing, diagnosing and treating the patient's plight, you will be the brain that science needs to evolve, you will be the lawyer who can help protect the rights of the patients and you will be and ARE the activist who can resist and refuse the current status quo. I would like to emphasize this last point. Thanks to your presence on university campuses, you are uniquely positioned to demand changes in the approaches of universities for specific compounds. We, at MSF rely on your activism. We rely on you to map public and university funding spent on key promising drug candidates in TB, hep C, HIV and vaccines and pressure universities to only sign a license agreement for these drugs when the agreement fully promotes open innovation and access. We also need you to help us push universities/researchers/academics to promote open, collaborative models of research & development, maximum transparency of R&D data, innovative ways to manage IP (e.g. pooling) and delinkage.

Conclusion

We have many challenges ahead of us. You are the present and the future of the access to medicines movement. We hope that you will be instrumental in changing the paradigm toward a needs-based R&D system. One that will be patient-centered. One that does not require years before better medical products reach patients. A system where physicians don't have to beg for more effective or less toxic drugs and where we – non-profit organizations - are not forced to invest in our own clinical trial to offset the inertia of the global health community. A system where science can benefit all patients at a just price, and where the priority of saving as many lives as possible takes precedence over profit.

In MSF, people come and go. Some do one field assignment. Others – like me - are involved with the organization for much longer. Regardless how long we've worked for this organization, our experience stays in us forever and changes our vision of humanity. UAEM and MSF have this passion in common. Whatever you decide to do in the future, I am convinced that your involvement at UAEM will always remain a source of inspiration and pride, and that the aspiration to address the patients’ needs will remain central to your work.

Thank you for your attention. It has been an honor to be able to speak to you today.

 

-Sophie Delaunay, MSF-USA Executive Director

 

Médecins Sans Frontières/International Union Against Tuberculosis and Lung Disease. DR-TB Drugs Under the Microscope, 3rd edition. Geneva: Médecins Sans Frontières/International Union Against Tuberculosis and Lung Disease; 2013 Oct.
MSF obtained estimates.

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