Transcript of BioCentury This Week TV Episode 157
Douglas R. Lowy, M.D., Deputy Director, National Cancer Institute (NCI), Chief, Laboratory of Cellular Oncology
Dr. John T. Schiller, Ph.D., Head, Neoplastic Disease Section, Laboratory of Cellular Oncology, Center for Cancer Research (NCI)
Sophie Biernaux, Vice President, Vaccine Development Leader, Malaria, GlaxoSmithKline Vaccines
Joe Cohen, Advisor, Malaria Vaccine Program, GlaxoSmithKline Vaccines
PRODUCTS, COMPANIES, INSTITUTIONS AND PEOPLE MENTIONED
Bill and Melinda Gates Foundation
World Health Organization
PATH Malaria Vaccine Initiative
Dr. Tom Frieden, Director CDC
Centers for Disease Control
Steve Usdin, Senior Editor
STEVE USDIN: When it comes to saving lives with vaccines, scientific breakthroughs are only the beginning. Today, you'll meet researchers whose work prevents cancer and may help tame malaria, but only if complex social and economic challenges are overcome. I'm Steve Usdin. Welcome to BioCentury This Week.
NARRATOR: Your trusted source for biotechnology information and analysis-- BioCentury This Week.
STEVE USDIN: In 2006, FDA approved the first vaccine against human papilloma virus, HPV. It was a remarkable achievement -- a vaccine that prevents cervical cancer, the second most common cancer among women. Based on research conducted by two NIH scientists, Doug Lowy and John Schiller, the HPV vaccine is a model for translating public science into effective medicines.
DR. DOUGLAS LOWY: This really is an achievement for the field of HPV research and the field of vaccinology.
DR. JOHN SCHILLER: It shows that overall, the people's investment in biomedical research is moving in the right directions.
STEVE USDIN: But it also shows that fantastic science is not sufficient to save lives. Unease about protecting children against a sexually transmitted infection and fear-mongering by vaccine opponents have reduced vaccination rates. According to CDC Director Tom Frieden, thousands will develop cancers that could have been prevented. HPV isn't unique. Other vaccines, including an effort to prevent malaria, must overcome economic and social barriers.
Later in our program, you'll meet researchers from GlaxoSmithKline, who are leading the effort to create a malaria vaccine. Right now, I'm pleased to have two scientists who made fundamental discoveries leading to lifesaving vaccines to prevent cancer, Doctors Douglas Lowy and John Schiller of the National Cancer Institute. I wanted to start by asking you -- you made fundamental discoveries that led to the creation of a vaccine that prevents cancer. Isn't it terribly disappointing that so few girls in the United States are vaccinated with it?
DR. DOUGLAS LOWY: Well, I certainly wish that more women had taken advantage of vaccination, but I suspect that over the course of the next few years, there will be increased uptake because so much of what the vaccine can do is actually being demonstrated, both here as well as in other places throughout the world.
STEVE USDIN: I want to get back to that a little bit later about what the benefits of the vaccine are, but to start with upfront -- if you go on the internet and you search for HPV vaccine, you're going to find thousands of hits talking about dangerous adverse effects. The government of Japan has expressed concern about it, the government of India. What's the data show about the safety of these vaccines?
DR. DOUGLAS LOWY: Yes, well, safety is really of paramount importance for a preventive vaccine such as the HPV vaccine, but the data really show that this vaccine is just about as safe as most other vaccines and really doesn't seem to have any showstoppers that would lead one to try to stop it. But this kind of analysis requires really prospective studies that are reasonably well-controlled. And people always get sick, no matter what age they are, with one disease or another, and sometimes it appears that the vaccine is causing it. But really, except for some allergic reactions, the vaccine doesn't seem to have major serious side effects.
STEVE USDIN: So, Dr. Schiller, one of the things that's interesting is that since the vaccine has come on to the market, there's been a greater understanding of the kinds of cancer that HPV causes, and in some of those actually occur in men as well as women. Can you talk about that a little bit?
DR. JOHN SCHILLER: Yeah, we have a much better understanding now that HPV is associated with a subset of oral cancers as well as anal cancer in men, and it's likely that the vaccine -- although it's not been demonstrated for oral cancer -- that the vaccine will also prevent those cancers, either directly by preventing the infection or because the oral cancers, we think, are sexually transmitted, it will reduce the total burden of the virus in the community and therefore secondarily prevent infection of the oral cavity. So we actually look forward to this vaccine not only preventing cervical cancer, but also oral-pharyngeal cancer and anal cancer in both men and women.
STEVE USDIN: We've got a little bit of time to talk about the science. I wanted to ask you both if you could describe very briefly -- what was the breakthrough? What was it that you discovered that led to these vaccines?
DR. DOUGLAS LOWY: Well, what we found was, if you just expressed one gene of the virus that it could make particles that look to the immune system as though they were the natural particles and they could induce very high levels of the kind of antibodies that usually are protective in preventive vaccines. And it turned out that those antibodies really seem to be the workhorse that confers protection by the vaccine.
STEVE USDIN: So you discovered that. You came up with a prototype vaccine, even. But then there was a hand-off to industry. Can you describe that a little bit? And how much work then had to be done to take that fundamental discovery and turn it into vaccines that are actually helping people?
DR. JOHN SCHILLER: An incredible amount of work. So once we had the proof of concept, it still had to be translated into a manufacturing process that could deliver millions of doses by a good manufacturing process technology, and then there had to be large clinical trials involving hundreds of sites and in tens of thousands of women. And so the companies really invested an incredible amount of money and effort and skill to develop these vaccines and bring them to the point where they could be FDA approved.
STEVE USDIN: And you mentioned FDA -- there's another kind of element-- it's a nuance, but I think it's a really important one, which was that you were able to get these vaccines approved based on a marker that indicates that they're likely to prevent against cancer. You didn't have to actually give the vaccines to girls and then wait 30 years to see whether or not they got cancer, right?
DR. DOUGLAS LOWY: Yes. Cervical cancer screening has been a very effective way of reducing the incidence and mortality from cervical cancer and it's largely based on the identification of precancerous lesions. And so for the development of the vaccine and its approval, using those same endpoints as are used for triggering treatment for cervical cancer screening, it was possible to develop strong data that the vaccine was highly effective.
STEVE USDIN: Both doctors Lowy and Schiller are working on new strategies that could make HPV vaccines less expensive and more effective. We'll talk about that in a moment.
NARRATOR: On September 11, Doctors Lowy and Schiller received the 2013 PhRMA Research and Hope Award for Academic or Public Research in Vaccine Development. You're watching BioCentury This Week.
STEVE USDIN: National Cancer Institute physicians John Schiller and Doug Lowy are working to improve the first generation of HPV vaccines. Today we're talking about ways to advance this ambitious goal. So, Dr. Lowy, Dr. Schiller, what are you doing both to try to reduce the number of doses that people have to get and also to widen the protection?
JOHN SCHILLER: Well, with regard to number of doses, there's been some interesting analyses that have been done since the vaccine was initially approved. For instance, the initial vaccine was given to young adult women, and it's been shown that in adolescent girls and also boys, their immune response is actually higher than it is in the young adult women that we showed protection.
As a matter of fact, two doses given at zero and six months give as high an antibody levels as three doses in young adult women or men. And so, there's the thought that maybe two doses would be sufficient.
STEVE USDIN: And that would lower the cost, but it would also increase adherence tremendously, wouldn't it?
JOHN SCHILLER: That's right. And therefore we wouldn't consider a girl who got two doses, or maybe even one, a failure. And in the Costa Rican trial, which was an NCI-sponsored efficacy trial for this vaccine, we also have some data in young women who only got one or two doses that we think that they also are protected, at least over a four-year period.
So, there's some evidence that we may actually be able to go down in the number of doses and still get protection.
STEVE USDIN: And what are you doing to try to create a second generation vaccine that would have broader protection, and why is that needed?
DOUGLAS LOWY: Well, with our colleagues, we are trying to pioneer an alternate approach using a different protein encoded by the vaccine that actually induces the class of antibodies that, rather than being more specific the way they are with the current vaccine, tend to be very broad in their spectrum before inhibiting infection.
STEVE USDIN: So, to translate what that means, basically, right now, the vaccines are on very specific strains of the HPV virus that cause particular kinds of cancer, or maybe in the case of one of the vaccines, particular other kinds of symptoms, and you're looking at something that's going broader against all of HPV.
DOUGLAS LOWY: Right. More than 10 different HPV types cause cervical cancer. And so it's important to try to develop a vaccine that can be as broad as possible to prevent as broad a spectrum of those infections. And so this candidate vaccine has that possibility, but it still needs to be tested in people.
STEVE USDIN: How far along is it, and what's the timeline for when you might be able to start testing it in people?
DOUGLAS LOWY: It appears that there are going to be early clinical trials started probably sometime next year. A lot of pre-clinical studies have been done in animals, and the data look quite good.
JOHN SCHILLER: But just to qualify that the current vaccines, although they are type-restricted, in other words, they only protect against certain strains, fortunately for us, two strains cause at least 70% of cervical cancer worldwide. So, they actually do a quite good job of potentially reducing the burden of cervical cancer all around the world.
STEVE USDIN: And can you talk a little bit about what's known now? Since the vaccines have been deployed for quite a while, how has it affected public health, and also, is there any kind of a herd immunity effect from it?
DOUGLAS LOWY: Well, I think in terms of public health, the biggest impact, really, has been seen in Australia, where there has been high uptake of the vaccine. And the vaccine is being used, also protects against genital warts. And in the group of young women who have received the vaccine, the incidence of genital warts has gone down dramatically.
But perhaps even more important, the incidence of genital warts among young men has also gone down substantially, which is evidence of herd immunity, which is that there is a decreased prevalence of the virus in the general population, and so this looks like it really could be a very good way of trying to reduce the incidence and burden of disease, not just by protecting people who are vaccinated, but also protecting people who aren't vaccinated.
STEVE USDIN: What they call herd immunity. Dr. Schiller, there's a lot of confusion around the fact that women get screened for cervical cancer, and we're also asking parents to have their kids vaccinated for it. Can you talk about the relationship between vaccination and screening?
JOHN SCHILLER: It's very important to point out that we need to continue, and even improve screening programs, even in the face of vaccination, for two reasons. First of all, the vaccine protects against 70% to 80% of the infections that cause cervical cancer, and we don't want the other 20% to get cervical cancer.
The other thing is that the vaccine does not cause the infections to go away once they're established, and so the vaccine will do very little for women, older women who already have their infections, and so we'll need to continue to screen them to make sure that these lesions that already exist don't go on and become cancerous.
STEVE USDIN: And so that actually is the key argument, also the key reason why the vaccine is recommended for administration to kids who are in the pre-teens, right? Because you have to --
JOHN SCHILLER: That's correct.
STEVE USDIN: You have to get them vaccinated before they get exposed to the virus.
JOHN SCHILLER: And the virus is very common. There's been studies in the United States, and also the UK that within two years of becoming sexually active, about half of the girls get one of these infections. So it really is very important to get the vaccine before you become sexually active, along with the fact that the vaccine actually works better in younger adolescents than in young women.
STEVE USDIN: Can you imagine a world where we don't have cervical cancer anymore? Where we don't have other cancers that are caused by HPV?
DOUGLAS LOWY: Yes, it certainly is now potentially possible, but it's going to take a long time, because the interval between the infection and the development of the cancers is usually decades. And so since you are using a vaccine that prevents infection, it's going to take a long time before you see the full impact of the vaccination.
STEVE USDIN: It's hard for people to understand that you're going to do something today that's going to prevent something that could happen 30 years from now. How long do you think it will be before, in a public health way, before we see this decrease in cervical cancers as a result of the vaccine?
DOUGLAS LOWY: In the countries that already have adopted a high uptake of vaccination, it will probably be about 20 years from the time that they started. So it may be around 2030.
STEVE USDIN: And another thing that I think is very interesting when you talk about different countries is that the public health impacts are going to be variable in different countries. Countries that have much less screening than the United States are going to have a much bigger impact from the vaccine, wouldn't they?
DOUGLAS LOWY: That certainly is true. Yes, because it really has to do with what the incidence of the HVP associated cancers are, and then if it's a high incidence, then you'll see a big impact. If it's a lower incidence, then the impact will be somewhat less.
STEVE USDIN: Well, thanks very much. The HPV vaccine was developed by two of our guests, and was the first of its kind to prevent cancer. Now another research team is nearing the end of a 30 year vaccine search against a complex parasite. In a moment, we'll meet two scientists who are developing a vaccine against malaria.
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NARRATOR: Now, back to BioCentury This Week.
STEVE USDIN: Malaria kills one African child every minute. The scientific barriers to developing an effective vaccine are formidable. Scientists at GlaxoSmithKline started working on a malaria vaccine in 1987.
Since 2001, GSK's been collaborating with the Bill and Melinda Gates Foundation. Early trials in adults were disappointing, but later trials showed it could cut the risk of malaria infection in half for children. Results from a trial in over 15,000 African children will be reported in 2014. They could pave the way for the first vaccine against one of the world's most lethal diseases.
I'm pleased to be joined by two key members of GlaxoSmithKline's malaria vaccine team, doctors Sophie Biernaux and Joe Cohen. Thanks both of you for coming all the way from Brussels to talk to us about this. I want to start with the idea that there are really two sets of challenges to developing a vaccine for malaria -- scientific challenges, and social and ethical challenges. And I want to start out with the scientific challenge.
Joe, you've been working on this vaccine for 30 years. You're a co-inventor of it. It's going to be the first vaccine against a parasite, if and when it gets approved. Can you tell us a little bit about why that's so difficult, and how you've overcome those challenges?
DR. JOE COHEN: Yes. Thank you having us. And yes, indeed, it's been a long time. I've worked on the malaria vaccine for 30 years. But the field has been working for 60 years trying to develop a malaria vaccine.
And as you mentioned, there are no vaccines against parasite, any parasite, today. The scientific difficulties are mainly related to the complexity of the parasite. The genetic complexity of parasite is an organism that's much more complex than bacteria or viruses. And the ability of the parasites to adapt to the human host and to escape the immune responses of the host -- these are the two main scientific reasons that made making a vaccine very, very difficult. In addition to that, the malaria parasites, when it goes through the human host, it goes through a number of stages where the parasite changes completely its form, if you wish. That makes the problem even more difficult to solve.
STEVE USDIN: So, Sophie, part of the problem also in dealing with this is that you had to create a whole infrastructure for testing vaccines in parts of Africa where that infrastructure didn't exist anymore. Can you tell us a bit about that? Where are you doing research in Africa? What have you had to do in those countries?
DR. SOPHIE BIERNAUX: This program shows that innovation is not just science behind discovering new drugs or vaccines, but also discovering innovation into new business model. And as soon as we get the proof of concept demonstrated in African population with discovering the vaccine, we enter into a partnership with the PATH Malaria Vaccine Initiative and with grant monies from the Gates Foundation. And together, we built an infrastructure in Africa in 11 sites in seven countries to initiate the Phase 3 part of our clinical studies, which is the late-phase development for the vaccine.
STEVE USDIN: So Joe, there's a lot of complicated things about this axiom, but one of them is communicating about what the efficacy of it's going to be. For most vaccines, people think very, very high efficacy rates that are going to last for long periods of time. It's a little different story with this one, isn't it?
DR. JOE COHEN: It's different, but it's not so different. Because at the end of the day for this vaccine as for any other intervention, the policy decisions are going to be made on the basis of the public health impact of the intervention.
STEVE USDIN: And so how can you describe in simple terms what the public health impact of this vaccine that has efficacy that varies from 30-50% in different age groups?
DR. JOE COHEN: To be very simple, I'll take data or results from that had been published from our Phase 3 study. And so what we see in the Phase 3 study is that in children five to 17 months of age, for every 1,000 child vaccinated and followed up for 12 months, 1,500 cases of malaria were averted. And in the infants where vaccine efficacy is a bit lower, in the 30 percentile, for every 1,000 child vaccinated and followed up for 12 months, 750 cases of malaria were averted. That's a tremendous impact, and compares favorably with existing vaccines that are being introduced, or have been introduced in Africa, and compare very favorably with other methods of prevention.
STEVE USDIN: Well, thanks. We're going to continue our conversation with researchers working on the world's most advanced malaria vaccine in just a moment.
NARRATOR: On September 11, the GSK Malaria Vaccine Team received the 2013 Pharma Research and Hope Award for biopharmaceutical industry research in vaccine development.
NARRATOR: We're discussing GSK's Malaria vaccine with Sophie Biernaux and Joe Cohen. Sophie, the world's best vaccine doesn't do anybody any good, if nobody gets it. What is it that you're doing at GSK and that you're working with Gates Foundation and others, to do to ensure access to this vaccine once it's approved?
SOPHIE BIERNAUX: So we at GSK, together with our partners, PATH MVI and Gates Foundation, we do not want that the price of the vaccine be a barrier for access. And so our CEO, Andrew Witty, made a commitment two years ago that, the malaria vaccine price will cost the cost of manufacturing plus a small return on investment, 5%, which will be reinvested into research on next-generation malaria vaccines or other neglected diseases.
STEVE USDIN: So the price of the vaccine is going to be GSK'S cost plus 5%. And then, that extra 5% is going to be ploughed back into doing new research. What's the timeline we're talking about for getting the vaccine approved? Just like everything else with this vaccine, it's terribly complicated, isn't it?
SOPHIE BIERNAUX: It's quite complicated. So we are still waiting for additional Phase 3 clinical data. But our intention, if everything goes well, is to submit a file to European authorities by next year. So we hope to have positive opinion from EMA by 2015.
STEVE USDIN: So step one is, you're going to submit data to European authorities next year. That's in 2014. By 2015, they hopefully give you an approval. Then what happens next?
SOPHIE BIERNAUX: Then we hope to have a WHO recommendation by end of 2015. And then we need to enter into all national regulatory authorization processes in the 42 countries in Africa.
STEVE USDIN: So you get WHO to give you a recommendation. And then, you have to go one-by-one, to 42 countries in Africa to get approval for this drug.
SOPHIE BIERNAUX: Yes.
STEVE USDIN: And the next challenge, I suppose then, is getting it paid for and getting it distributed to kids who need it. How's that going to work?
SOPHIE BIERNAUX: So we are working again together with partners, under whose financing might make a need, such as GAVI or organizations who are really taking all the finance to make sure that this is not the children and the family who are really the paying for the vaccine. And so it should be at no cost for the children.
STEVE USDIN: So the Dr. Biernaux mentioned a second generation, Joe. What are you looking for in the second generation? What would be the characteristics of it that might be different from the first generation? And is it possible to even think about timelines?
JOE COHEN: Timelines, that's a bit far, no. But yes, there is a team at GSK that is working on a second-generation vaccine. It's looking into approaches that combine proteins from different stages of the parasite, to target several of these stages. It's looking at improving the overall efficacy of the vaccine. It's looking into potentially developing a vaccine against the other, the second medically most important parasite that causes malaria, plasmodium vivax.
STEVE USDIN: So we have to take a step back there and also point at, which I haven't said. It's that this vaccine is against one particular strain of malaria that is prevalent in most of Africa. But there are other strains that are in some parts of Africa and other parts of the world. And they're not going to be addressed by this vaccine.
JOE COHEN: That is correct. This vaccine is targeting one strain that is prevalent in Africa. Essentially, above 90% of all cases of malaria are due to this strain. And it's also targeted towards young children and infants.
STEVE USDIN: Thanks very much. That's this week's show. I'd like to thank my guests John Schiller, Doug Lowy, Sophie Biernaux and Joe Cohen.
Remember to share your thoughts about today's show on Twitter. Join the conversation by using the hashtag #biocenturytv. I'm Steve Usdin. Thanks for watching.