When Climate Bites | Controlling the Spread of Dengue Fever

Sanofi Pasteur dengue vaccine receives expedited approval in endemic areas.

Over the past decade researchers have seen a dramatic rise in the incidence of infectious diseases including dengue, chikungunya, SARS, and zika virus.[1] Mathematical modeling has been used to understand potential relationships between climate variables and biologic parameters such as mosquito breeding, survival, biting rates, and parasite incubation time.  Changes in environmental variables such as ocean warming, elevated precipitation, urbanization, and urban crowding have also been linked to the rising incidence of mosquito borne diseases in previously unexposed regions.[2]  Modeling of new dengue fever hot-spots has suggested that small temperature increases can play a significant role in disease transmission.[3]  Specifically, models of a global temperature increase of 2-3ºC have predicted a 3-5% increase in the risk of dengue infection, which amounts to several hundred million new cases per year.[4] In the 1960’s, less than ten countries had experienced severe dengue epidemics.  Now, over 100 countries in the WHO regions of Africa, the Americas, the Eastern Mediterranean, South-East Asia and the Western Pacific, have seen dengue spread to their shores.[5]

Dengue fever is transmitted between people through the bite of infected female Aedes aegypti mosquitos. The WHO has set the objective of reducing dengue related mortality by 50% and morbidity by 25% in endemic countries by 2020. Their strategy to reduce the transmission of dengue includes infection prevention, mosquito control, public education, and vaccination. [6] In 2016, the first dengue vaccine, Dengvaxia made by French pharmaceutical giant Sanofi, was registered and distributed in several countries with the goal of reducing the global burden of dengue fever.[7]

Dengvaxia was produced using Sanofi’s ChimeriVax technology platform which is based on a yellow fever viral backbone.[8] Given the rising burden of dengue, Sanofi received “fast track” status in 2010 from the U.S. FDA and became the world’s first dengue vaccine to start Phase III trials.[9]  The FDA fast-track designation “recognized that a dengue vaccine would address an important unmet medical need for a serious disease” with increased incidence trends linked to climate change.[10] In anticipation of a common challenge in vaccine development – the shortage of vaccine manufacturing and process development capacity[11] – Sanofi strategically invested in a €300 million production facility in France well in advance of the Phase III efficacy trial.  This facility has been operating since 2014 and has a yearly production capacity of 100 million vaccine doses.[7] Dengvaxia is currently approved for use in Mexico, Brazil, the Phillipines and El Salvador.[12]

Given its recent success launching Dengvaxia, I would encourage Sanofi Pasteur to leverage its unique manufacturing platform and the readiness of regulators to fast-track clinical steps to accelerate the simultaneous development and Phase I testing of multiple new vaccine candidates.  While Sanofi has announced a plan to develop a vaccine against Zika virus, their 2016 Letter to Shareholders doesn’t mention growing the R&D pipeline.[9] In addition to investing in product development, Sanofi should focus on streamlining its clinical trial processes which rely on decade-old technology and suffer from bottlenecks in data transferring.[13] By optimizing early clinical trial processes, Sanofi can promote rapid data acquisition and processing to facilitate smart decision making. By focusing on manufacturing excellence, Sanofi will continue to be a world leader in the vaccine industry.

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[1] Patz, J.A., et al., Effects of environmental change on emerging parasitic diseases. Int J Parasitol, 30(12-13): p. 1395-405 (2000).

[2] Wilson, M.L., Ecology and infectious disease, in Ecosystem Change and Public Health: A Global Perspective, J.L. Aron and J.A. Patz, Editors. 2001, Johns Hopkins University Press: Baltimore. p. 283-324.

[3] http://www.climatecentral.org/blogs/the-climate-connection-to-dengue-fever

[4] Hales, S., et al., Potential effect of population and climate changes on global distribution of dengue fever: an empirical model. Lancet, 360: p. 830-834 (2002).

[5] World Health organization. Dengue and severe dengue. Factsheet No 117.

[6] World Health Organization. Global strategy for dengue control and prevention 2010-2020. Geneva: WHO, 2012. Available at: http://apps.who.int/iris/bitstream/10665/75303/1/9789241504034_eng.pdf. Last accessed on November 4, 2016.

[7] Thomas, Stephen. “The Necessity And Quandaries Of Dengue Vaccine Development”. Jid.oxfordjournals.org. N.p., 2016. Web. 4 Nov. 2016.

[8] Gray, N., Sanofi CEO wants to leverage Dengue vax success to expedite Zika vaccine development. 2016, BioPharmaDIVE. Available at: http://www.biopharmadive.com/news/sanofi-ceo-wants-to-leverage-dengue-vax-success-to-expedite-zika-vaccine-de/413671/. Last accessed Novemeber 4, 2016.

[9] March 2016 Letter to shareholders. Retrieved November 4, 2016, from http://en.sanofi.com/Images/46626_Letter_to_shareholders_03_2016.pdf

[10] Sanofi Pasteur Announces Publication In The Lancet Of World’s First Efficacy Results For Its Dengue Vaccine Candidate. European Pharmaceutical Review. N.p., 2016. Web. 4 Nov. 2016.

[11] IAVI Report – Breaking The Bottleneck”. Lavire Port. 2016. Last accessed on November 4, 2016.

[12] Sanofi Pasteur. Sanofi Pasteur Dengue Vaccine Frequently Asked Questions – July 2016.

[13] McDonald, C., Vaccines 2016: Big Bets for Global Threats. 2006, Pharmaceutical Executive. 36 (3). Available at: http://www.pharmexec.com/vaccines-2016-big-bets-global-threats. Last accessed on November 4, 2016.


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Student comments on When Climate Bites | Controlling the Spread of Dengue Fever

  1. Since Dengue and Zika viruses are members of the flavivirus family, it makes perfect sense that Sanofi’s is planning to use their yellow fever viral backbone as a platform to develop a Zika virus vaccine. Other companies such as Merck, the US government, and handful of small biotech companies are following a similar strategy, therefore, it is promising that one of these companies will develop an efficacious vaccine. One concern I have are timelines for the drug approval process. Even though Sanofi’s Dengvaxia has been approved in five countries to date (Mexico, Brazil, Philippines, Costa Rica, and El Salvador), the Zika virus variation of the yellow fever viral backbone platform will require genetic modifications that create a new biologic that will require process development, manufacturing, and Phase I-III clinical trials, and its own separate BLA (Biologics License Application). While it is likely that there will be process redundancies, my big concern are the timelines it takes to perform each of these activities. While I am not a regulatory expert, Sanofi may be able to bypass or combine Phase 1 and 2 clinical trials as bridging studies to the Dengvaxia clinical trials. Even if this is possible, I still would estimate the process taking at 4-5 years before commercial launch. If this is the case, do you Sanofi (or some other company) will be able to distribute the vaccine in time to prevent Zika transmission of epidemic size to other parts of the world? Do you think the FDA should give Sanofi (or some other company) fast-track approval like the do for orphan diseases?

  2. I really enjoyed this informative article. Especially its structure was clear and easily understandable. That the climate change leads to the spread of disease is undeniable and I see how Sanofi finds a way to produce new vaccine to fight these diseases. But why does the pharma industry not build alliances dedicated to fighting dangerous diseases? Why are so many companies developing their vaccines alone? Is it the competition and the goal of maximizing margins that that prevents company of working hand in hand together? When I read this article, I was questioning whether the human health is the stimulating factor in the development of new drugs/vaccines or how much influence profitability has? In my perfect world there would be pharma cooperations working on the most pressing health problems with shared costs and shared profits and faster development cycles. But as I feel, this is not possible and so, I hope that there are companies such as Sanofi which continue their great work and help fighting the consequences of climate change.

  3. Thanks for the interesting, user-friendly post for those of us without a healthcare background! What was interesting to me is that one could argue this company (at least for this drug) is actually benefiting from climate change in terms of profit potential. They’re able to receive more governmental support for the development (fast-track process) and a larger potential base of consumers given climate change. I wonder if there is reduced demand for other drugs as a result of climate change? If not, is Sanofi’s “environmental commitment” (http://www.sanofi.us/l/us/en/layout.jsp?scat=A7257D49-ED84-4C9A-8699-F2A0B9526A68) inspired purely by the values of a healthcare company?

  4. Yes, these diseases are an increasing concern, especially because of the way they spread. e.g. dengue through mosquito bites. India also saw a doubling up of cases of dengue from 2014 to 2015 and the worst hit city was Delhi with over 1800 cases of the fever. A lot of these cases result in death of the individual because of improper care. One form of prevention is curbing the spread and mating of mosquitos, which is something the Indian authorities are working on extensively. In a way this is in line with helping reduce water wastage as mosquitos breed in high stagnant water.

  5. What a fascinating article highlighting the threat infectious diseases will continue to pose in an increasingly interconnected world, especially under the pressures of climate change. Building off of Andrea’s comment above, I’m curious to understand how Sanofi intends to price (or has already priced) Dengvaxia. As of April 2016, the company stated that it had not yet decided on pricing, but according to the head of the Vaccine Unit at Sanofi, the vaccine would remain “affordable” and its “economic value will be higher than its cost” (http://www.wsj.com/articles/sanofis-dengue-vaccine-dengvaxia-recommended-for-use-by-who-1460715657). Given that Dengvaxia took decades to develop, I imagine Sanofi will have to carefully consider how to recoup its R&D costs; how will the company balance this consideration with providing rapid access to a vaccine that’s urgently needed, especially in developing countries where patients’ ability to pay is likely very low? Linked to the question of what is the “right” price is who, ultimately, will pay if patients cannot afford the vaccine? In the infectious disease space in global health more broadly, prevention, treatment, and program costs are often shouldered by donors (e.g., the Global Fund to Fight AIDS, Tuberculosis, and Malaria covers a significant percentage of the cost of many countries’ HIV, TB, and malaria programs). Is it realistic to think that a multilateral donor or individual governments will step in to pay?

  6. I fully share your concern for what seems to be an already immediate threat of climate change. And while I think Sanofi’s initiative to develop a dedicated vaccine makes sense, to echo Andrea’s concerns, I am afraid this could actually turn the impact of climate change into a lucrative business. Similarly, the fight against malaria, which is also thought by some studies to be exacerbated by climate change (http://www.who.int/globalchange/climate/summary/en/index5.html) is creating a more legitimate case for genetically modified mosquitoes (http://www.bbc.com/news/health-34898931). I am genuinely afraid that these lucrative externalities of climate change are resulting in a series of perverse incentives that might end up slowing down the fight against climate change and shifting it towards a far less sustainable, yet profitable “accommodation” business, which will again be primarily carried on the shoulders of the more exposed developing world.

  7. Thanks for a great article! One of my favorite topics is thinking about the spread of disease and how best to contain it, and you are absolutely right in how climate change will exacerbate other contagious illnesses. While there is an obvious benefit to being able to fast track the clinical trial and FDA approval processes, is there a potential for Sanofi to diversify? For example, in addition to the development of novel vaccines, I wonder if there is a potential for them to partner with researchers working on genetically modified mosquitoes (http://www.theatlantic.com/technology/archive/2016/04/genetically-modified-mosquitoes-zika/479793/).

  8. Thank you for the article. Sanofi has indeed done a great job in developing the dengue vaccine – a projected it had worked on for around two decades; so it is great to see success come from the project. However, Sanofi must be aware of the impending competition from Takeda, who are currently in the process of taking their dengue vaccine through phase III trials (https://www.ft.com/content/2eb5c618-74f4-11e6-bf48-b372cdb1043a). Some data suggests that Takeda’s vaccine may prove more efficacious, and this could lead to a price ware with Sanofi. It is important for Sanofi to therefore capitalize on its first mover advantage by signing up for large vaccination programs with countries affected by dengue, as it has been doing, with large vaccination programs already launched in Philippines and Brazil. With time, climate change has the potential to shift mosquito distribution – which could in turn impact on dengue distribution, and therefore with time, which will provide Sanofi with a shifting geographic target market.

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