Medicines and Vaccines Part 2: Bringing Essential Medicines to Market

In our last piece, we talked about the pharmaceutical development pipeline and how some drugs are repurposed from other medicines, rather than being discovered as a new medicine completely. In this post I’ll talk about what that pipeline looks like for antibiotics and vaccines, two of the most important types of medicines that we have.

Vaccines and antibiotics, like all medications, are very expensive to produce (as we discussed in Part 1), but they can’t be sold for the same high prices as nonessential (think Viagra) medications. This creates a problem for the development pipeline: how can companies afford to take risks on new development for products that won’t cover the cost of producing them? The answer was surprising for me when I first started studying public health.

Antibiotics

The repurposing method is often used for antibiotics, though they continue to be a low priority for commercial development. In part because of this method, no new, major classes of antibiotics have been found since 1987 and only, “two systemic antibacterial agents have been approved for use in humans by the U.S. FDA from 2008 through the current year,” compared to sixteen approvals from 1983-1987. [1] At the same time (for a number of reasons including use in animals and improper prescription in humans) drug-resistant and multi-drug resistant infections are on the rise, creating a “perfect storm” on the horizon of a world in which simple infections and surgeries become deadly because there are no effective antibiotics to treat them.

To understand why the need for antibiotics is so dire, it may be helpful to understand what antibiotics are, how they are synthesized (created) to make medications appropriate for use in humans, and what “resistance” is. Antibiotics are the means by which microorganisms battle one another—they’re the tools of (micro)biological warfare. When a bacterium evolves a new way to avoid (resist) those attacks, it’s more likely to replicate and pass on that trait. Those bacterial offspring are also more likely survive and eventually you end up with an entire population of bacteria resistant to that attack. That’s essentially what antibiotic resistance is: germs that can survive an assault with a certain drug are more likely to reproduce, increasing the number of germs that won’t be killed by that medicine.

Historically, classes of antibiotics have only been discovered in readily-accessible soil. This means that the antibiotics that humans synthesize were already in use by the microorganisms around us, lessening the time between when they are approved for market and when resistance starts to appear. Penicillin, the first antibiotic discovered, was already experiencing resistance even before it appeared on the market. [2] Understanding that the need for new antibiotics is pressing and time is short, some adventuresome microbiologists are searching for new compounds in lakes and oceans. Recently, the Toronto Star did a series on researchers from the University of Illinois at Chicago who are searching for new compounds in the waters around Iceland and have found some promising new compounds. [2]

In a fashion less like Indiana Jones and more like typical lab work, Seattle-based IDRI in 2014 announced a partnership with the pharmaceutical giant Eli Lilly to codevelop new antibiotics to treat mycobacterium tuberculosis (TB), which Lilly will then manufacture. [3] Lilly has elected to ship their catalogue of reactants to IDRI for this purpose, a significant investment in the project, as noted by IDRI’s vice president of drug discovery Dr. Tanya Parish. [9] For a company like Lilly, investing in the development of antibiotics is prohibitively expensive using their own researchers and facilities, but, by partnering with an organization like IDRI, those research and development (R&D) costs are significantly offset. [3] IDRI and groups like them operate as nonprofit organizations, allowing them to focus their R&D budgets on expensive, but unprofitable, ventures like the development of TB medications, which cannot be so expensive that they are inaccessible to the world’s poor who bear the greatest disease burden. IDRI’s funding is predominantly grant-based from large foundations like the National Institute for Health and the Bill and Melinda Gates Foundation, which have both the resources and desire to invest in this kind of research. [4]

Vaccines

Vaccine development has also benefitted from partnerships like the one between IDRI and Eli Lilly. Seattle-based PATH, in partnership with pharmaceutical behemoth Merck, created the Rotateq vaccine to combat rotavirus, which is responsible for the deaths of half a million children under 5 each year and is the leading cause of hospitalization for US children in the same age group. [5] Though vaccines are one of the best investments in public health in terms of quality-adjusted life years (QALYs), they, like antibiotics, cannot be sold for the amount necessary to make a profit.

PATH has a similar funding structure to IDRI, and so is well placed for developmental partnerships like the one with Merck to tackle non-chronic conditions, particularly the “diseases of poverty” and those primarily effecting women and children.

Not all vaccines are the result of a profit-nonprofit partnership, of course. Seatte’s Center for Infectious Disease Research’s (CIDR) GAP malaria vaccine is the result of initial funding from organizations like the Bill and Melinda Gates Foundation, which awarded CIDR the funds as part of their global initiative to fight malaria. The Gates Foundation has continued funding the program through their Grand Challenges program. [6] The Gates Foundation has malaria eradication as a key initiative and is, therefore, funding research on medications, vaccines, and other vector control measures at a number of other institutions, including PATH, the Medicines for Malaria venture, and both the London and Liverpool Schools of Tropical Medicine. [7]

The road to developing a vaccine is a complex one, with a number of different types of vaccines to prevent diseases from a litany of bacteria and viruses, as well as the ongoing task of developing a vaccine for the parasite plasmodium, which causes malaria.

Some vaccines were relatively easy to develop (anthrax) or were completely accidental (smallpox), but for diseases like HIV, the task is complicated by the difficulty of finding the optimal mechanism to target, effectively carrying it out, and crossing the hurdle of high variability (the amount of variation in strains of the same infectious agent).

This issue of high variability is particularly problematic for HIV, which rapidly mutates because of the method of its replication and is prone to superinfection. Superinfection—contracting multiple strains of the same disease—can both accelerate the disease’s progress and hinder treatment efforts. The picture below shows the diversity of the HIV virus, giving an idea of the difficulty of finding a vaccine and the need fora high level of investment. Which strain(s) get the vaccine? How do you choose how to attack the virus? It's a tough job!

Variation in HIV Strains (University of California, Berkeley)

The Take Away

Developing new pharmaceuticals, whether drugs or vaccines, is time-consuming and extremely costly, making it impractical for pharmaceutical companies—which for better or worse exist to make a profit—to invest their R&D funds to the discovery and development of remedies for which no profit is possible. It is also completely unacceptable to charge hundreds of dollars per pill for an antibiotic or dose of a vaccine.

In 2014, Gilead released a medication for late-stage kidney and liver cancer costing $69,000 for a year of treatment. [8] CEO was quoted saying that his company develops drugs for, “western patients who can afford it,”[8] not poor Indians. There have also been controversies about the astronomical price hikes for devices like the epi-pen that are essential for keeping people alive. While Gilead and Mylan are certainly entitled under United States law to seek to make profits from the sale of medications, allowing the commercial market to drive the development of lifesaving treatments leaves the world vulnerable to preventable disease and death.

While the health of people who live in poor nations is far worse than in the United States, we also have our homeless and prison populations suffering from TB, malaria was once prevalent in the United States, [9] and last summer Florida had a number of Zika cases. [10] A world without effective antibiotics would have the same dire consequences for Americans that it would for other populations—surgeries happen everywhere and it only takes one fall on broken glass to develop community-acquired MRSA infection, as I learned after a very unfortunate hangover-induced fall down a rocky hillside a few summers ago.

In our next piece, we’ll do a “quick and dirty” overview of how vaccines interact with your immune system and how the vaccine schedule was developed.

Spellberg, B. New Antibiotic Development: Barriers and Opportunities in 2012. Association for the Prudent Use of Antibiotics. 2012; 30(1) http://www.tufts.edu/med/apua/news/news-newsletter-vol-30-no-1-2.shtml
Yang, J. Antibiotic Hunters. Totonto Star. http://projects.thestar.com/antibiotics-resistance-and-the-race-for-new-bacteria/#one
IDRI and the Eli Lilly Company. Lilly and IDRI Partner to Speed Development of TB Treatments. April 2014. http://www.youtube.com/watch?v=KUso0onZiLc
Funding Partners. Infectious Disease Research Institute. http://www.idri.org/funding-partners.php
Rotavirus Vaccine Access and Delivery. PATH. http://sites.path.org/rotavirusvaccine/
Malaria. Seattle BioMed. http://www.seattlebiomed.org/disease/malaria
Update on Gates Foundation Malaria Grants. The Bill and Melinda Gates Foundation. http://www.gatesfoundation.org/Media-Center/Press-Releases/2008/03/Malaria-Partners-Letter
Peck, A. Pharmaceutical CEO: Cancer Drug Is Only For Westerners Who Can Afford It. Think Progress. 26 January, 2014. http://thinkprogress.org/health/2014/01/26/3205861/pharmaceutical-ceo-cancer-drug-westerners-afford/
Chikungunya Virus in the United States. Centers for Disease Control and Prevention. http://www.cdc.gov/chikungunya/geo/united-states.html
Zika Virus. Florida Health. http://www.floridahealth.gov/diseases-and-conditions/zika-virus/

By: Amanda