Pneumococcal vaccine complexity

Hey there bathhousers,

Wow, haven’t done one of these for a while but I just learnt something and feel the urge to share. I’ve been reading about how vaccines work and also about the geographical variation of disease.

This brings me to today’s post which as sciency as it gets round here so hold on to your autoclaves and let’s get stuck in.

Invasive pneumococcal disease kills over 1.5 million children each year according to the World Health Organization (WHO), Ninety percent of these deaths occur in the developing world. [1][2]

You might think that if a vaccine is available in Europe and the US then it should be made available in the developing world too. One of the main vaccines for Pneumococcal disease is called Prenvar. Prevnar is among Wyeth’s top revenue producers, with sales in 2005 of $1.5 billion. [3]

So on the face of it there is an effective vaccine used in Europe and the US that should be rolled out across Africa, seems like a straight forward case where the drugs exist, Pharma has recouped their investment from Western consumers, so there is a moral imperative to bring this drug to the people that need it. Perhaps, within our current system of IP as long as the rich world needs the same drugs then they can pay for the R&D costs and everyone can get the benefit, assuming the minefield of international IP law can be negotiated.

Unfortunately it’s not as simple as that. There are around 90 different bacteria (serotypes) which cause pneumococcal disease. Prenvar is formulated to prevent 7 of those strains. Unfortunately the prevalence of different strains varies geographically. The table below shows the results of a study to determine the relative prevalence in descending order for the developed and developing world [4]. Bear in mind that ‘developed’ and ‘developing’ represent huge areas so there is likely to be a large amount of additional variation between regions. (the number represents serotype number)

Developed 14 6 19 18 9 23 7 4 1 15
Developing 6 14 8 5 1 19 9 23 18 15 7

The table below shows the 7 serotypes present in Prenvar and a new GSK drug Synflorix.

Prenvar 14 6 19 18 9 23
Synflorix (GSK) 14 6 19 18 9 23 1 5 7

You’ll notice that the Prenvar vaccine is designed to prevent the most common strains in the developed world, as you might expect. Unfortunately the 3rd, 4th and 5th most common forms of the disease in the developing world are not covered by this vaccine.

This example illustrates why even if access to drugs developed for the developed world could be assured, in some cases, the efficacy wouldn’t be the same. Furthermore, If you’re going to go to the trouble to run a mass vaccination for a disease that kills millions, you’d at least want a drug that treated most of the common strains in your country, otherwise it could be expensive and ineffective.

Also in the table you can see another drug developed by GSK.  Synflorix, which as you can see covers two of the missing serotypes and is therefore  likely to add to the overall effectiveness significantly in the developing world. But if the missing serotypes aren’t prevalent in the developed world why did GSK develop this drug?

It was possible because of an advanced market commitment from Gavi [5] (the Global Alliance for Vaccines and Immunisation). This means that Gavi have committed to buying up to 300 million doses over 10 years and in return for this GSK have developed the drug.

In conclusion, in some cases the developing world will need drugs developed specifically for their own needs. Where there aren’t rich consumers with insurance companies and government funded healthcare, innovative financing mechanisms like advanced market commitments or perhaps publicly developed and owned IP will be needed to ensure that drugs get developed.

[1] http://en.wikipedia.org/wiki/Pneumococcal_conjugate_vaccine

[2] (http://www.who.int/vaccines/en/pneumococcus.shtml

[3] http://en.wikipedia.org/wiki/Pneumococcal_conjugate_vaccine#cite_note-pmid17324490-11

[ 4] (Pediatric Infectious Disease Journal
Volume 14, Issue 6 http://www.scopus.com/record/display.url?eid=2-s2.0-0029057617&origin=inward&txGid=z2jb5-sWfwbAl6CATF7Gvif%3a2)

[5] http://www.gsk.com/media/pressreleases/2009/2009_pressrelease_10012.htm

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2 thoughts on “Pneumococcal vaccine complexity

  1. Thanks for this post Rich. I’ve become increasingly intrigued by the GSK pneumococcal vaccine story and so I’m very pleased to see this issue being looked into. From what I’ve learned in the past few weeks, there’s a whole lot more to this story. The more you dig, the more complicated and twisted it becomes. For now though just a couple of issues.

    The 2 dose vial controversy: Sarah Boseley has drawn attention to the fact that GSK originally developed this vaccine for rich country markets where it is sold in the form of a one dose vial [1]. The vaccine being offered through the GAVI AMC however, is only to be sold as a 2 dose vial. GSK say this is because it’s somehow better for developing countries [2], but I would imagine that concerns about the parallel importation of a cheaper vaccine from poor to rich country markets are in fact the primary motivation for this change in presentation. The reason for suspecting a commercial motivation rather than the altruistic ‘it’s better for them’ motivation is that the WHO has insisted that the 2 dose vial be pre-qualified before it can be rolled out across Africa, which means that apart from Kenya where GSK have received WHO approval to trial this form of the vaccine and collect data on how it is used, the vaccine will not be delivered to a single child in Africa until 2012 at the earliest. It is therefore not the most expedient way to ensure these children are vaccinated. The 1 dose, 1 child version used in rich country markets would not have needed these extra studies since it is already pre-qualified.

    Moreover, the reason the WHO are insisting on data collection before approving the vaccine, is because of the way the 2 dose vial works: it requires that the person administering the vaccine draw up half the contents of the vial for one child and then use the remaining half on a second child. The WHO want to see evidence that a vaccine packaged in this way will be used correctly, since it is more complicated and has more scope to be misused than a straight forward: one vial for one child version.

    It is difficult then not to suspect that GSK are motivated by commercial concerns rather than public health ones, and that the acres of positive coverage they received along with the GAVI donors for (not quite) rolling out a vaccine, has not presented us with the whole story.

    Also a comment on the AMC, following from Rich’s post. The GAVI AMC describes it’s function as, ‘accelerating innovation, creating new vaccines, saving lives.’ [3]. The development of this pneumoccocal vaccine wasn’t stimulated through the AMC, it already existed, so it’s an overstatement to say at this stage that the AMC has led to ‘new vaccines’, unless we count the repackaging of the existing vaccine into the ‘developing country’ version… The AMC will (in the next few years after the vaccine has been pre-qualified) save lives by encouraging the roll out of a vaccine in a context where it would otherwise have been unlikely to have been purchased. However, what’s still desperately lacking are mechanisms that will encourage R&D that focuses on health needs rather than market needs. As Rich’s post shows, the vaccine was designed to target the serotypes most prevalent in the rich country markets and in fact misses two of the most common strains in the developing world.

    We need mechanisms that allow research and development to be oriented towards the health needs of all populations and not only those that can express their needs in the form of a lucrative market. So far the AMC has been left wanting. This is why the decision made on Friday at the World Health Assembly to form a consultative Expert Working Group on R&D Financing and Coordination is so important and holds so much promise [4]. New ideas must be brought to the table and investigated. What we have at the moment is inadequate to address the magnitude of the public health problems we face. New thinking that leads to new mechanisms is desperately needed.

    [1] http://www.guardian.co.uk/society/sarah-boseley-global-health/2010/may/11/vaccines-infant-mortality

    [2] http://www.guardian.co.uk/society/sarah-boseley-global-health/2010/may/13/vaccines-pneumonia

    [3] http://www.vaccineamc.org/

    [4] http://www.ip-watch.org/weblog/2010/05/21/world-health-assembly-creates-new-initiative-for-rd-financing/

  2. Obviously I know very little about all this, but don’t these dynamics cry out for government-led investment in R&D. Similar in the way that some MICs have worked on their weapons industries – partnering with ‘friendly’ countries and the like. And while small developing nations obviously don’t have the finance can’t they link-up in regional blocks – like they do with trade partners – to jointly fund medicine development? India leading research for South Asia, Thailand for East Asia, South Africa for sub-Saharan Africa? Is it a case that the politics of cooperation would be to flimsy? Or is it simply that the expertise would be lacking?

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