Students in the Philippines began receiving doses of the world’s first dengue vaccine this week, as the country begins a public immunization program to inoculate 1 million children in 6,000 schools across the island nation.
Dengue, a mosquito-borne disease which causes severe flu-like symptoms, is particularly endemic in Asian countries. In response, the Philippines government has been quick to seize on the public health opportunity presented by the vaccine, developed and marketed by Sanofi Pasteur as dengvaxia.
However, the amount of time, money, and effort expended to develop Dengvaxia demonstrates the challenging cost calculus required to bring a new vaccine to market. Sanofi Pasteur spent 20 years working on dengvaxia, enrolling over 40,000 volunteers in 25 clinical studies. On top of this heavy investment burden, vaccines typically command lower prices than other drugs, making the commercial case for vaccine development less compelling for pharmaceutical companies. From a public health standpoint, however, vaccines are vital for large, at-risk populations.
This combination of need and challenging economics leads Dr. Jim Tartaglia, global vice president of new vaccine projects at Sanofi Pasteur, to believe novel partnerships between companies are vital to continue pushing R&D money into new disease areas.
No more low hanging fruit
Speaking with BioPharma Dive last week during the World Vaccines Congress in Washington, D.C., Tartaglia emphasized vaccine development will rely more and more on novel partnering mechanisms.
“Most, if not all, of the low hanging fruit are gone in vaccine development. So you have key vaccine R&D challenges that result in increased development costs, stress on volume and price, and reduced return on investment,” he explained.
These costs expand beyond just clinical trials and materials. Tartaglia cited heightened manufacturing and quality compliance standards, as well as the need for larger safety databased to meet regulations.
With increasing costs, partnerships can help improve the economics behind investing in a potentially long and costly development process. Partnerships over the course of R&D can also help with resource commitments, allowing companies and organizations to bring complementary capabilities to the table.
“At the end, I think these are the types of partnerships that are necessary for us to do things not just from a commercial perspective, but also from a social responsibility perspective where we are playing our part with industrial capabilities,” Tartaglia said.
For Sanofi Pasteur, Tartaglia estimated roughly 50% of the company’s portfolio was partnered in some way, usually in the earlier development stages.
A novel partnership example
As an example of this new model, Tartaglia pointed to the P5 Partnership and its work developing an HIV vaccine. The P5, an acronym for Pox-Protein Public Private Partnership, is made up of a broad group of pharma companies, NGOs, and government groups: Sanofi Pasteur, Novartis Vaccines, GlaxoSmithKline, the National Institutes of Health, the Bill and Melinda Gates Foundation, the HIV Vaccine Trials Network and the U.S. Military’s HIV Research Program.
In 2009, Sanofi Pasteur collaborated on a Thai study, known as RV144, which gave the first evidence a preventive HIV vaccine was possible in humans. Although efficacy after three and a half years was only 31%, a higher response after one year sparked hopes of further development.
Building off of that, the P5 last year launched an early stage trial in South Africa with a modified design and schedule of the RV144 vaccine regimen. This trial used a two-part regimen made up of canarypox-based vaccine from Sanofi Pasteur and a protein vaccine from Novartis, along with a booster shot administered after one year.
A Phase 2b trial is planned to begin this fall and aims to achieve a vaccine efficacy of at least 50% after three years.
The South African trials demonstrate the flexibility and complementary contributions Tartaglia sees as necessary for moving vaccine development forward. Sanofi and Novartis manufactured the test vaccines for the early study, the NIH and The Bill and Melinda Gates Foundation co-funded it, and the HIV Vaccine Trials Network conducted the trial work.
A tougher R&D environment might also push companies to look more carefully at platform technologies which could be used as a foundation for new vaccines. Sanofi is using this approach in its hunt for a Zika virus vaccine.
Dengvaxia is based on technology known as Chimerivax, which modifies the yellow fever virus by removing the surface part of the virus and replacing it with the dengue virus’ surface molecule. Sanofi hopes to replicate this approach with the Zika virus, which like dengue is a flavivirus and is transmitted by the same type of mosquito.
“We are using our network, our involvement in dengue, and our platform technologies that have been successful with dengue towards Zika to hopefully nudge it and deal with things in the immediate term but the longer term as well,” Tartaglia said.
Companies like Sanofi also must deal with a paradigm shift in distribution where the initial disease burden is in low to middle income countries. Rather than developing vaccines first in the developed world and recouping investment through sales there, Tartaglia saw vaccine efforts increasingly taking place in developing countries which may not be able to afford prices necessary to cover initial R&D efforts.
In his view, this only adds to the case for moving forward with partnerships. “The receptivity is there because I think people sense this is necessary for success, especially in thinking about global public health responses.”