"It's Time for a Faster Cure"

Transcript of March 19, 2003 Press Teleconference Hosted by the Global Alliance for TB Drug Development

Speakers:

• Joelle Tanguy, Global Alliance for TB Drug Development
• Dr. Bernard Pecoul, Medecins Sans Frontieres/Doctors Without Borders (MSF)
• Dr. Doris Rouse, Research Triangle Institute
• Dr. Charles Yu, Philippines Coalition Against Tuberculosis (PHILCAT)

G. Oosterbaan:

Good morning and good afternoon to those of you joining us from Europe. I'm Gwynne Oosterbaan and I handle all media and communications here. I'd like to thank everyone for participating on the call today. We know that a war is about to begin in Iraq, which is a pressing matter for many of you. I'd like to just emphasize that the war on disease never stops. In fact, TB remains one of our greatest and most dangerous enemies. Of infectious agents, tuberculosis is still the single deadliest, and this year marks an important milestone in the war on TB. Ten years ago, the WHO, the World Health Organization, declared TB a global emergency. More than ever, TB remains today a major global health threat.

On Monday we'll be hearing from the WHO on the state of the epidemic. To put those figures into perspective, our speakers today are going to address why new drugs for tuberculosis are "must have's" in the global war on TB and how we can develop them. We're very fortunate today to have speakers with a wide range of global health expertise. They have a wide range of expertise in TB, public health, policy-making and drug development. Our first speaker, Joelle Tanguy, is the Director of Public Affairs and Advocacy here at the TB Alliance and had previously led medical and humanitarian operations worldwide as well as global health campaigns. Joelle?

J. Tanguy:

Hello and thanks for participating in this call. One of the reasons why we are making this call today is because admittedly, of all of the global health threats plaguing us today, no other disease, really no other disease is as prevalent and yet as overlooked.

One-third of the world is infected. That's a fact that few people really realize. And someone dies every 15 seconds. That's why we are hoping that you will cover the TB epidemic on World TB Day. What we wanted to feature today is a more underreported feature of this epidemic: the fact that one of the main reasons the disease has gotten so much out of hand is because we are relying on drugs that are 30 to 50 years old and simply take far too long to work.

Ten years after the World Health Organization declared TB as a global emergency only a less than a third of TB patients that have access to proper treatment.

As a consequence, TB is not just an emergency, it has reached epic proportions. If you want to think about it this way, you can think of it as a triple threat. Threat one is its rapid spread: one person gets newly infected every second. The second threat is its deadly symbiosis with the HIV epidemic. TB kills one in three AIDS patients, and in places like Sub-Saharan Africa, it's two of three AIDS patients. The third and deadly threat is the lethal rise of resistant strains, MDR-TB, which now is estimated around 400,000 cases a year. It requires two years of therapy with toxic drugs and has no guarantee of a cure.

How did outdated TB drugs play into this disaster? Well, today's TB drugs take about six to nine months to complete for the simple treatment of a non-resistant strain. To maximize compliance the treatment strategy involves the almost daily monitoring of the patient taking the drugs, or directly-observed treatment. That's the best strategy today, but over a long period of treatment time, this involves significant costs for all patients and for public health systems alike. In practice, that translates into a real difficulty of implementation, of expansion of access to treatment. You can think of it as this: today's drugs are the Achilles' heel of drugs today's best treatment strategy, which has the potential of reversing the epidemic.

This is a conclusion where public health specialists and others involved in TB came to two year ago and decided that we absolutely needed to develop a new, short acting drug. Two months seems to be a magical time for people like us who have to face such a lengthy regimen now, six to nine months. But that's also really, we know, something that should be feasible and will fundamentally transform the way we can fight tuberculosis. Thousands of lives will be saved, and access will be greatly improved, and many more people will be able to be treated.

So the question came, how can we do it? Clearly, that was a sobering question. The current market structure, the current built-in incentive into the tuberculosis markets were not going to yield new drugs. The last new drug was introduced in the 1970s and was actually a product of even earlier research. So think about it. We needed a new approach to drug development. That is how the Alliance came to be formed.

We could not expect a single operator in the industry to carry forward drug candidates and guarantee the development of a new drug, but if we actually brought together public and private capacities, we probably could do it. That's what the thought was two years ago. Now it's a reality. The Alliance is bringing together public and private labs and expertise and best practices. We're designing agreements between all of those players by trying to make sure that they are win/win agreements, kind of transforming the incentive structure. We're developing a new bottom line in practice, a shared objective of an affordable and accessible drug. That's how this joint approach allows us to tap expertise of public academic and industry labs all over the world.

You may have heard several months ago of an illustration of this in the mention of a new agreement with Chiron, the U.S. biotech company. It was really an expression of our business model at work where the deal ensured that technology moved on, but no royalties would be imposed on endemic markets.

I want to emphasize how far we've come in two short years. We've identified drug candidates. We've put them in the R&D chain, and we're moving them off lab shelves towards the clinical trials. We are also really moving forward and in practice have demonstrated that there is now a reasonable, logical best model, best approach to meeting an unmet medical need that the market could not address in decades. We're pretty excited about this progress, and to mark World TB Day this year, we are calling on those leaders in government and in industry to join us fully in this endeavor so that we can make the goal of a faster cure a reality.

I think that recent news from the industry was, in some ways, very encouraging. For example, Novartis had opened a new research facility in Singapore last month devoted to TB. They pledged the fruits of their research to initiatives such as the Global Alliance for TB Drug Development and committed to the TB Alliance model of no royalties for endemic countries. That's a really great development. AstraZeneca also has a similar facility in India. I think that all this is proving that they are willing to take the fruits of their research and shepherd those compounds from discovery stage into final stage of development with us. We urge other companies to do the same.

When we look at the TB epidemic, to conclude, I think we need to understand that we are all at risk. This is a global public health issue. So worldwide global cooperation is key. It's not only a public/private partnership. It's a global public/private partnership that will take whatever capacity exists around the world and focus it on a commitment to deliver a novel and affordable drug within the shortest time possible. We are hoping that you will feature this and highlight this often underreported aspect of the TB epidemic today: In what other deadly diseases are we dealing with tools that are 30 to 50 years outdated?

G. Oosterbaan:

Thank you very much, Joelle. Now, we're going to Bernard Pecoul, Director of Medecins Sans Frontieres (MSF)'s Access to Essential Medicines campaign. I'd like to take this opportunity to thank Bernard and MSF for their support in the formation and the development of the TB Alliance. Starting as a volunteer physician at MSF in the 1980s in both Thailand and Central America, Bernard also ran the MSF operations in France for seven years, overseeing a total of over 100 different field projects. Dr. Pecoul also co-founded and directed research and training at Epicenter, an epidemiological research organization in Paris. Dr. Pecoul also speaks Spanish and French, and should we have those fluent in those languages and would like to ask questions in Spanish or French, we can definitely accommodate that. Joelle Tanguy is also fluent in French. Bernard?

B. Pecoul:

Good morning. Today, Medecins Sans Frontieres is working on tuberculosis in 20 different countries and want to testify that we need faster-acting drugs.

In all countries we operate in, we use DOTS, the recommended strategy. We implement this project in totally different settings such as in Siberian prisons and in various settings and countries in Asia and Africa. I think we are, consequently, in a good position to make comments on how difficult it is today to treat TB patients and to try to reach the ambitious objectives set up by the world community to control the disease. Personally, I was involved in a TB treatment program and using these outdated drugs in 1985 and 1986 in Thailand, and what I can say today is that there is nothing new. We are still using exactly the same outdated tools. So what difficulties are we confronted with?

First of all, in TB treatment today, we are still using microscopic tests, which have been developed by Mr. Koch in 1880, so 120 years ago. It's a time to develop better tests, because these current approaches are very difficult to use at a country level. To prevent tuberculosis, our only option today is to use a BCG, a vaccine developed during the 1920s and which is not a very effective vaccine. To treat TB, the last important antibiotics have been discovered during the 1960s. So we are still using very old drugs.

Finally, when we are confronted with more and more drug resistant strains because of the long treatment. Today to treat MDR-TB we are obliged to use a cocktail of very toxic and very complicated old drugs that the people have to take together without a very high percentage of cure or success.

So the situation is quite despairing, and I think it's not with this kind of tools that we will reach the objectives set up by international leaders of reducing TB mortality in half by 2010. How will that happen? We need new tools. That is a clear message. If we want to make progress, we need new tools to simplify the management of the disease at each level. That's diagnosis, treatment and prevention.

To develop these new tools, I think the first condition is to have clear support from governments, from the public sector. When I talk about government, I am referring to all countries - from the most affected countries to the donor G-8 governments. These countries need to bring money on the table as well as science because I think a lot of research in the public sector today can assist in the efforts to improve the tools.

We need also to force the companies, pharmaceutical companies, to be more involved in the business of tuberculosis. What is apparent today is tuberculosis is no longer a part of the core business of these companies. I think everybody agrees on that. They will not change dramatically their strategy towards tuberculosis.

What I'm requesting of companies is mainly two things. One, companies offer access to existing compounds. So if they have general antibiotics, which have some efficacy against tuberculosis or existing compounds that they have in the pipeline that could be to facilitate the development of new TB drugs. Second, companies have very important libraries of compounds so they're a critical reservoir for new promising compounds. They need to open the library to initiatives such as the Global Alliance. I think this is essential. It will speed up the process. I'm not asking companies to put a lot of money on the table. I'm not asking the companies to change their strategy. I'm just asking the companies to use their knowledge, to use their expertise, and also to use human resources because I'm sure that the researchers within the companies will be very pleased to contribute to some new developments for tuberculosis.

These last comments are definitely not limited to TB, I think the same steps and contributions from industry can be applied to all neglected diseases. For those very reasons, in the coming months, Medecins Sans Frontieres will be engaging in a wide campaign to increase investment into R&D for neglected diseases. Thank you very much.

G. Oosterbaan:

Okay. Thank you, Bernard. Our next speaker is Dr. Doris Rouse, who is the Project Manager for the development of one of the compounds in the portfolio of the TB Alliance. The effort that she oversees is supported by NIAID at the National Institutes of Health. Dr. Rouse also serves as the Head of Global Health at the Research Triangle Institute International in North Carolina. In the year 2000, Dr. Rouse managed the working group that wrote the TB Alliance publication on the economics of TB drug development.. Doris?

D. Rouse:

Okay. Thank you. The focus of this phone discussion as well as the Alliance is really how can we develop and make available more effective and affordable drugs for treating TB. A key element of effective and sustainable development of new drugs is to form partnerships between industries, universities and public organizations, both philanthropic and government. The reason for these partnerships is we need the resources and the expertise across all of those sectors in order to be successful in developing new drugs.

Industry knows how to develop, manufacture, test, market and distribute new drugs. Universities and the public sector have quite a bit of knowledge in basic research and funding resources. We need to bring all of those resources and expertise together in order to be successful and to be able to sustain the development, because this will take some time. It will take a lot of involvement by different groups.

The TB Alliance is playing an important role, serving as a catalyst to bring these elements together. Although they're a nonprofit entity, they are going about this catalyst role and this product development in a very business-like way. They're involving industry and their advisory groups. All of their development activities are done in very much of the business model.

A good example of that is that early on, the Alliance understood that a pharmaceutical company needed, if they were making a decision on whether to become involved in the development of a new drug, they needed to make an informed business decision. In order to do that, they needed the data. There was a study done by the World Health Organization in the late 1990s interviewing various companies to find out what they saw as the incentives and the disincentives in becoming involved in developing new TB drugs. A surprising response was that most companies thought that the market worldwide for TB drugs was about $150 million. No one had actually gone in and looked at what the market was, and so we couldn't give them other data.

The Alliance, when it really first started in 2000, commissioned this study to be done, to look at what would be the market for new TB drugs, what would be the cost for development. We looked at really two markets that exist. One is the private market, which is traditional pharmacy and hospital sales both in established economies and developing economies. Then the other market, besides private, is the public market. It's sometimes called the tender market. That's government purchases at the national and regional and local level as well as international donor purchases.

What we did in order to provide industry with the data, the business data they needed on the potential market for a new TB drug was to acquire information on both of these. So the private market, we went to a standard industry source for private sales that they use for all of their market projections. A company called IMS Health was kind enough to actually donate their data to this project. For the public market, we worked with the World Health Organization to survey the national and donor agencies for their purchases.

The results were really quite interesting. The total market in the year 2000, rather than being $150 million as the industry perceived it to be, was conservatively estimated to be $470 million. I say conservative because especially for that public market, we were unable to get data on the local and regional purchases within countries. So that's a fairly conservative estimate, much higher than the $150 million.

Surprisingly, the majority of these sales, $275 million, were in the private market. More than half of the private market sales were actually in the high-burden countries with a developing economy. So that data was quite surprising. Then we did a projection of the total market for TB in the year 2010, which is the year the TB Alliance is targeting, and I think it's an ambitious estimate for a new drug on the market. Our estimates for that is $700 million for total TB sales that year.

We did a calculation of what a new drug that could reduce the period of treatment from two months versus the current fix, and it would also be active against some multi-drug resistant strains of TB. The market for a new drug of that sort would be between $400 million and $430 million in the year 2010, which is not an insignificant market for a company, certainly for a smaller biotech company. It should interest both large and small. That's where the Alliance plays a role.

The business model for the Alliance, as I said, is to take a very business-like approach to the development of a new TB drug, to build a portfolio of promising anti-TB compounds that will be developed through outsourcing to both public and private sector laboratories worldwide, and to support projects that will fill in infrastructure gaps that are there to streamline the process. The Alliance identifies drug candidates in public and private sector labs. It negotiates intellectual property rights with the owners of those compounds. The focus in that negotiation is to balance the affordability and health equity, that is to be sure that these compounds can be provided at an affordable price in the endemic countries that most need them, but also develop the incentives for industry collaboration.

Joelle mentioned the agreement that the Alliance developed with Chiron Corporation to license this first compound, PA-824, in which Chiron can acquire the rights for marketing the compound in established economies, but the Alliance will keep the rights for marketing in the developing economies so they can keep the control over the affordability and health equity issues. To develop this portfolio and to find these compounds and to take them through the development process, which is long and expensive, the Alliance finds in-kind contributions from a variety of donors and creates synergies with key partners in both the pharmaceutical industry and the public sector.

It has developed a very effective development process that's efficient and uses outsourcing to keep costs down, to provide a very flexible approach to drug development. The goals of that development process are to advance the compound quickly and efficiently, to utilize capabilities and infrastructures of research organizations on a global basis, and to provide a thorough scientific review throughout the process with specific go and no-go decision points involving experts from industry, academia and government organizations involved. I could address the many ways that the industry can become involved in developing a new drug for TB. For example, the National Institute of Health, specifically, the National Institute of Allergy and Infectious Diseases, has been working in the discovery and development of new drugs for TB for quite a while.

One element, I think Bernard mentioned that companies could provide access to their library of compounds as one way to participate. But they may not know how to test those compounds for activity against tuberculosis, but this National Institute of Allergy and Infectious Diseases has a program for no-cost screening of new compounds. It's done on a confidential basis. Proprietary rights are protected, and they will screen compounds for activity against tuberculosis.

If the results are promising, then they will work with the owner of that compound to form partnerships and to conduct additional testing, perhaps testing in animals, and even it goes through into clinical trials capability is available also through NIH. There are a number of resources that are available to help companies identify and then reduce their cost and their risk for developing a new compound for TB. The Alliance is playing a catalyst role to help bring all of that together.

G. Oosterbaan:

Thank you, Doris. Now, we go to Manila, where Dr. Charles Yu will bring us up to date on the situation of fighting TB on the ground there in the Philippines. A specialist in tuberculosis and also a practicing pulmunologist, Dr. Yu is a professor at the University de LaSalle and is also the chairman of PHILCAT, the Philippines Coalition Against Tuberculosis, a public/private collaboration of 52 organizations working to improve TB control in the Philippines. Established in 1984, PHILCAT is currently working to stimulate TB initiatives in the Philippines.

C. Yu:

Okay. Thank you and good day to everyone. I'd basically like to outline what I'm going to say. One is, as has been said, what the situation is here, what PHILCAT and public/private collaboration can do, and how important it is in the fight against TB. Finally, what we think is important work from the Global Alliance for developing new drugs.

First of all, we literally live in the frontlines in the battle against TB in the Philippines. I see TB patients daily. I see patients dying. It is estimated from a study that was done by Dr. Peabody from the Institute of Global Health that for every 100 new TB case in the Philippines, 25 of those die, and probably they die for a multiplicity of reasons. They don't consult the proper health care facility or they're treated too late, and or they are victims of the big problem of multi-drug resistance in the Philippines in which a new drug would really be, believe me, be very, very important.

Now, the Philippines is a high-burden country. It's number seven worldwide among the 20 top high-burden countries. In the western pacific region, we're actually number two after Cambodia. We see 75 Filipinos dying of TB every day. That translates to a minimum of 27,000 reported deaths. It's also estimated by the study that I mention that this actually is an under estimate because many of them are never really reported. So you can just imagine. Reportedly, economic losses from TB amount to almost 10% of our gross domestic product, or around 27 billion pesos from one year along from foregone wages. It's a huge economic impact.

But more than that, I'd like to share with you really the agony and suffering that people go through from a disease that should be cured and can be cured if there were just effective drugs that we can give. One of the problems in TB is because it takes too long to treat and many people don't finish their medicines. Now, we know there's a great problem in the Philippines, and that's why ten years ago the Philippine Coalition against tuberculosis was founded initially with seven organizations representing academia, the government as well as the professional society. Now we have growth 52 organizations strong, representing thousands of health providers as well as TB patients.

We were invited as one of the stakeholder groups in the Global Alliance for TB Drug Development last October in Canada, and I shared with the people there that, and I think I can share it here, it's about time a new drug was developed. Too many people have died. There have been millions that have died needlessly because there is no effective drug that has come out over the past 30 years. We need that drug because millions of people are dying from tuberculosis.

PHILCAT is a great example of successful partnerships and we strongly supported the government's Department of Health DOTS program, to push the detection rate and the cure rates and we talked about our role here in Montreal at the IUATLD annual conference on TB. The Philippines decided that a possible success story by 2005 if we get our act together, and it looks like the signs are all pointing very well towards that as long as we do our thing in both private and public sector because one third of the TB patients in the Philippines consult the private sector.

Finally, I'd say the next step, we need to support a movement like the Global Alliance for TB drug development. If we can cut the treatment from six to nine months to two months, that will save millions of lives. Many of our patients cannot take the medicines for too long, even with the DOTS. That will create a huge positive move in our battle against tuberculosis if we can cut down the drug to two months.

Maybe finally, I can say that maybe the target for the new drug should be 4 "S." It should be safe. It should be short. It should be simple and maybe just novel therapy and it should be sure and eventually maybe it should be affordable. We would really like to endorse from the battleground of TB that the Global Alliance should be supported. There should be investments, long-term investments to this because one of the twins of tuberculosis is poverty. If we can defeat TB, we can lower down poverty and this can lead to better health and a better life for all of us in the world. Thank you.

G. Oosterbaan:

Thank you, Dr. Yu. I just want to point out that the qualifiers for the new drug that Dr. Yu emphasized are the exact profile of the Alliance's new drug that we have identified. It must be short acting.. It must combat MDR-TB, so it has to be a novel therapy. And it must reduce the length of treatment for latent infections.

We'd like to invite questions from our participants now and I'd like to offer the first one.

G. Oosterbaan:

Thank you, Dr. Yu. I just want to point out that the qualifiers for the new drug that Dr. Yu emphasized are the exact profile of the Alliance's new drug that we have identified. It must be short acting.. It must combat MDR-TB, so it has to be a novel therapy. And it must reduce the length of treatment for latent infections.

We'd like to invite questions from our participants now and I'd like to offer the first one.

Question:

Can you could describe in more detail what governments can do today to ensure that we meet the Millennium Declarations. You referenced in your comments earlier that the goal is to reduce in half the mortality from tuberculosis. Could remind us of the connections between TB and poverty and economic development, and why governments must be involved in this process?

B. Pecoul:

Okay. Maybe I will make a first comment. I think one of the characteristics of tuberculosis is that this disease is touching the poor in the countries. Tuberculosis is really targeting the most disadvantaged people. It's another reason why governments have really a big responsibility to get organized in the response to tuberculosis.

As I mentioned in my presentation, governments from developed countries have a key role to play, in supporting the effort of tuberculosis drug development because if we have some good candidates, some good compounds, I think we need to have a clear support from endemic countries to do much of the development activity. I'm particularly thinking on all of the clinical trials, all development can take place in the most affected countries because that's really the place where we need this drug. So it's a place where the activity can and should take place.

Governments in other countries should also motivate their pharmaceutical companies from developing countries to be involved in research and production of drugs for tuberculosis. But my last message, of course, is for the rich countries. Today, it's really an important responsibility from the government to support initiatives such as the Global Alliance. It is important to have a concrete solution for tuberculosis within five to ten years. Today, I think that governments can contribute much more, in terms of financial resources to the Global Alliance. So I think my clear message in 2003 is to convince the rich countries to put money on the table in order to have new drugs to treat tuberculosis patients.

G. Oosterbaan:

Okay. Thank you. What I'm going to do now, unless we have another question, for the concluding remarks is invite each of our speakers if you'd like to make a final comment. Then we'll conclude with a sign-off remark from Joelle Tanguy here at the Global Alliance. But, Doris or Charles, if you have any other statements or points that you'd like to make before we close, you could do so at this time.

D. Rouse:

Well, I would like to just close with saying I think everyone has made a very good case for the need for new TB drugs. It's quite clear that that's needed. It is an expensive and long process, and support is needed to accomplish that. In-kind support is essential from industry; for example, they might provide their expertise and likewise, financial support from governments and philanthropic organizations is equally important. It really is going to require an investment, but as everyone has said, well worth it in terms of the human cost and a financial cost to the world. That would be my concluding remarks.

G. Oosterbaan:

Okay. Thank you. Charles?

C. Yu:

Well, I'd also like to end with one comment and actually a small story. We need to endorse and support the efforts of the Global Alliance, because that is a much needed key element in the battle, if we are to defeat this menace of a TB problem. I'll end with a little story. In this part of the world, there has been a huge panic caused by this news about the sudden acute respiratory syndrome that seems to be going and frightening so many people all over the world. When I was addressing a large group of media people yesterday, and I asked them the question, "Why are you so afraid of the SARS? It only killed nine people over 150 reported cases at that time. You don't worry about Filipinos, 75 of whom are dying every day."

So maybe we should pay attention to the neglected diseases like TB and this one got their attention because it is the one that is the clear and present danger in our country and in many countries all over the world. So please hurry up with the new drug, and we would be very, very happy to celebrate the breakthrough or the release of a new drug for all of our TB patients. Thank you.

G. Oosterbaan:

Thank you. Bernard, do you have any comment you'd like to close with?

B. Pecoul:

Yes, a very, very short comment. I think, of course, we need cooperation from all partners to be more responsible. When it comes to reversing tuberculosis, the leadership should clearly come from the public sector, from the government. We need this kind of leadership to be the only way to reach the objective and the convenience.

G Oosterbaan:

Thank You Bernard. Joelle, a final remark?

J. Tanguy:

Well, as you World TB Day approaches, I'd like us all to consider one point. Many rare diseases have constituencies that wish they coul influence public policy and R&D agenda better than they do, but rarely will you encounter a disease that is so prevalent and has actually nobody standing up for the patients. Tuberculosis is a disease of the poor or the marginalized. It is unfortunately a disease of the voiceless.

There is no poster child for TB, no Hollywood figure to call attention and priority on developing the necessary tools to better combat this epidemic, so we're really counting on you to echo what you heard from our speakers today involved in trying, beyond witnessing the progress of this global threat, to do something about it. We count on you, and thank your for participating.

G Oosterbaan:

I'd like to just close and thank everyone for joining the call today. We do know that there's a lot going on, and we are very appreciative of your attention and hope that you will be able to write on World TB Day. It's marked on March 24, next Monday. If anyone has any further questions on the Alliance or the work here, please feel free to give me a ring, and we'll be in touch shortly. Thank you, operator, as well.