Europe: A Future Leader in Vaccines?

Few people are aware of just how powerful a force Europe is in the R&D of vaccines. This is important given the fact that the earlier part of this decade saw the number of pharmaceutical companies making vaccines steadily decrease and those still active scaling back their R&D efforts. While this trend could be partially explained because of industry consolidation, the main reason for the decline was commercial factors, with some companies feeling that the R&D expense for vaccines was not being sufficiently offset by revenue gained in the marketplace. Indeed, vaccine sales tended to fall well below the level of revenue being brought in from major pharma products; in 2005, for example, it was calculated that among the top four pharma companies making vaccines, these products accounted for less than 6% of total revenue.¹ Another worry for vaccine manufacturers was the impact of safety concerns and product liability lawsuits. As an example of how serious a risk this is, a 1986 lawsuit stating that pertussis vaccine caused paralysis in a child resulted in the jury awarding $1.1 million, which worked out at more than half of the entire market for pertussis vaccine at the time!¹

Nathan Jessop

Bouncing back

Although growth for certain segments of the vaccine market has been affected by under utilisation of available vaccines (e.g., for measles), the vaccine market, as a whole, is now entering a period of expansion. During the past 5 years, overt measures to encourage vaccine manufacturers has helped give a boost to the sector, largely thanks to government interest in preparing for influenza pandemics and combating bioterrorism. Other specific measures have also been taken to make life easier for the industry; for example, in the US, the risk assumed by vaccine developers has been eased through the Vaccine Injury Compensation Programme, a national fund that compensates families whose children are injured by vaccines.

Market growth is expected to occur primarily because of the introduction of new vaccines against diseases for which no vaccine currently exists or as second-generation products to replace existing vaccines.² It has recently been predicted in the US media that vaccine sales would double from $19 billion in 2009 to $39 billion in 2013.³ In particular, cancer vaccines are expected to be a major driver of future market growth because of the promise they have already shown for preventing disease, as well as the receptiveness of the market for dealing with cancer using this approach. In the UK, for example, uptake rates of the cervical cancer vaccine were around 80% between 2009 and 2010, leading to predictions that cases could be cut by around 63% by 2025.⁴

Recently, there has been considerable media attention concerning Dendreon's (WA,USA) innovative prostate cancer vaccine Provenge, which was launched in the US in April 2010. Between June and July, sales more than doubled to $5.2 million, but the company's manufacturing is reported to be struggling to keep up with demand.^5–7 One of the problems with Provenge is that, unlike other drugs, eligible patients must have their cells shipped to a laboratory where a customised immune therapy is prepared, which takes about a month. Prior to FDA approval, the company had been hesitant to expand manufacturing in case of a negative opinion, but is now under pressure from patients to boost production. The company is expected to reach full manufacturing capacity by early 2011.

Within the current market, the most successful vaccine product is Pfizer's Prevnar 7, which protects against seven strains of streptococcus pneumoniae.⁸ In 2009, Prevnar 7 had global sales close to $3 billion, which put it among the company's top products. Pfizer is now developing Prevnar 13, which protects against 13 strains of the bacterium. The vaccine is already approved in Europe and the US for infants and children, but the company is running trials with the aim of expanding into the adult population.⁹ If this approach is successful, it could add an extra $1.5 billion in annual product sales.

However, Pfizer may well be facing competition in this area from GSK's Synflorix, which was approved in Europe in 2009. In the same year, GSK also signed a 10year $1.5 billion agreement with the Brazilian government for supply of the vaccine,¹⁰ although the company has not yet made a decision about launching it in the US.

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The European sector

The expansion of the vaccines market should bode well for Europe where the vaccines industry is particularly strong — in part thanks to the European Vaccine Manufacturers (EVM) group, which was formed in 1991 and is a specialised group of the European Federation of Pharmaceutical Industries and Associations (EFPIA). The EVM routinely carries out surveys of its members to track the R&D performance of the sector in Europe and to lobby governments where appropriate. EVM members are the largest supplier of vaccines in the world. Although they have a number of international sites, these companies conduct half of their R&D in Europe.^11,12

According to the EVM's latest regional analysis (from 2008),¹³ members were running 122 vaccine R&D projects; among these, 29 had reached Phase III trials. A further 22 projects were undergoing Phase IV testing in the post-approval environment, such as including special populations, which may not have been included in earlier registration trials. The EVM also likes to highlight the emphasis on innovation, explaining that, of the new vaccines introduced since 2003, over 60% have been based on new antigens. EVM data also show that there has been a strong growth in vaccine R&D investment; vaccine R&D investment was around €2.1 billion in 2008, which represented an increase of almost 40% since 2002. Employment in the European vaccines sector also rose between 2002 and 2008 by 58%.¹²

Vaccine development is also being facilitated through the European Vaccine Initiative (EVI), which is currently being created from what was known as the European Malaria Vaccine Initiative (EMVI).^14–16 EVI's work focuses on neglected diseases and seeks to validate promising vaccine candidates that emerge from European laboratories. As with EVM, the EVI highlights Europe's strong expertise in the vaccine field, stating that the region is the home of 60% of global vaccine R&D. In February 2010, along with partners, the EVI received €9900000 from the European Commission for the 4year TRANSVAC project. Translational research is a bottleneck in the European vaccine research system, so one goal of TRANSVAC is to assist groups in handling the complex and costly clinical development of vaccine candidates.

The H1N1 Pandemic

Through 2009, a new influenza virus (H1N1) emerged to which many people had no pre-existing immunity. Considerable media attention focused on cases where the H1N1 virus led to deaths in younger, apparently healthy people. During this period, the H1N1 strain began to crowd out other influenza virus strains leading to WHO declaring a pandemic alert.¹⁶

Although the H1N1 pandemic created a new area of demand for the vaccines industry, it also presented it with developmental challenges in meeting expectations. A complication was that commercial production was already underway for other influenza viruses predicted to make a global impact when the industry was suddenly asked to change course and divert resources to tackle H1N1. However, this could not be done as fast as people expected since a traditional and time consuming process was initially used, where the virus was first grown in chicken eggs and then harvested it into vaccines. It took some time before the major manufacturers were able to successfully demonstrate the advantages of cell-based alternatives. For example, only by June 2009 was Novartis able to announce that its cell-based manufacturing technology system had shaved off weeks from the expected vaccine development time.¹⁷ By this time, it had already received orders from 30 governments. Similarly, GSK was under pressure after signing an agreement with the WHO to donate 50 million doses of its pandemic H1N1 influenza vaccine.¹⁸

However, it now seems that the vaccines industry has become a victim of its own R&D success. Because the pandemic did not reach the severity predicted by WHO, the pharma industry has been accused of exaggerating the threat to secure orders for its pandemic vaccines. In 2009, for example, Reuters calculated that GSK would receive £2.2 billion from government orders for its pandemic vaccine.¹⁹ The vaccines sector in Europe undoubtedly received a boost, with Novartis' manufacturing sites in Marburg (Germany) and Speke (UK), GSK's manufacturing site in Rixensart (Belgium) and Sanofi Pasteur's facility in Val de Reuil (France) being responsible for meeting much of the global demand.

In August 2010, the WHO officially declared the H1N1 pandemic over, but the controversy over the vaccines industry's activities in promoting the use of its products continues. One of the better outcomes of the pandemic situation is that vaccine R&D is now based on cellbased systems rather than traditional egg-based processes. This has been accepted by regulators as the way forward for future vaccine development.

In summary

Vaccines have represented an important tool in combating infectious disease and may eventually find a place in treating chronic diseases such as cancer. After a dip in activity during the early part of the decade, manufacturer interest in vaccines R&D is slowly being rekindled because of government initiatives and new public health threats. The highly organised European vaccines sector is particularly well placed to benefit from renewed market opportunities; however, it needs to tread carefully, as public concern over industry profits leaves the commercial sector open for criticism, as well as praise when it responds to new healthcare challenges.

References

1. in-Pharma Technologist, "Vaccine decline must be halted, says opinion leader" (2005). www.in-pharmatechnologist.com

2. L.A. Johnson, US News and World Report, "Vaccine 'Revolution' on Horizon for AIDS, Alzheimer's, Herpes" (2009). www.usnews.com

3. Synbiosis, "Rapid Assessment of Vaccine Potency" (2009). www.synbiosis.com

4. The Telegraph, "Cervical cancer vaccine will cut cases by two thirds, experts calculate" (2010). www.telegraph.co.uk

5. FiercePharma, "Provenge scrips hit 500 as payers agree to pay" (2010). www.fiercepharma.com

6. WSJ Health Blog, "The Provenge Dilemma: Who Gets Dendreon's New Therapy?" (2010). http://blogs.wsj.com

7. Bloomberg, "Prostate Cancer Patients Face Rationing of Provenge" (2010). www.businessweek.com

8. New York Times, "Vaccine Approved for Child Infections" (2010). www.nytimes.com

9. BioPharma Today, "Prevnar 13's Added Strains, Extra Studies Help Insulate Pfizer's U.S. Position" (2009). www.biopharmatoday.com

10. GlaxoSmithKline, "GSK Fourth Quarter Results" (2009). www.gsk.com

11. European Vaccine Manufacturers (2009). www.evm-vaccines.org

12. European Vaccine Manufacturers, "Vaccines' contribution to Europe's future" (2010). www.evm-vaccines.org

13. European Vaccine Manufacturers, "EVM statement to the Council of Europe hearing" (2010). www.evm-vaccines.org

14. European Vaccine Manufacturers, "Human vaccines: New questions for European Vaccine Initiative" (2010). www.emvi.org

15. TRASVAC. www.transvac.org

16. CIDRAP, "More clouds in H1N1 vaccine supply picture" (2009). www.cidrap.umn.edu

17. Novartis, "Novartis successfully demonstrates capabilities of cell-based technology for production of A(H1N1) vaccine" (2009). www.novartis.com

18. WRAL.com, "World Health Organization certifies GSK's H1N1 vaccine" (2009). www.wral.com

19 in-Pharma Technologist, "GSK's H1N1 orders total 440m doses" (2009). www.in-pharmatechnologist.com