For a research based on value. The failed model of antibiotics

Cristina Roure

As we have commented on some occasion in this blog, neither the price nor the volume of investment in R&D of the medicines corresponds to the value they provide. Antibiotics, along with vaccines, have saved millions of lives, have allowed to address challenges such as transplants and complex surgeries with guarantees of success and, if this were not enough, they also add enormous value to the productivity of the agricultural sector.

But these benefits that we take for granted are at risk and now we are talking about returning to the pre-antibiotic era. Every year at least 700,000 people die in the world due to infections caused by resistant microorganisms and it’s estimated that this figure will raise to 10 million in 2050, well above the expected deaths due to cancer, chronic diseases such as diabetes or traffic accidents (1). The projections also speak of a cost of 100 trillion dollars per year. It is, therefore, a global health emergency but also economic.

Despite the urgent need to remedy this situation, the development of antibiotics is practically frozen and no new group has been developed for more than thirty years (2).

The pharmaceutical industry, so active in cancer or chronic diseases, lacks incentives for research and development in this area. The value given to antibiotics does not correspond at all with the benefits they generate in society, which seems to be more willing to pay exorbitant amounts for palliative treatments with marginal benefits or to medicalize the problems of life than to invest in research and preserve curative treatments that save millions of lives and benefit large sectors of the economy.

This innovation gap is explained by the combination of important scientific-technical and commercial barriers:

• The research and development of a new antibiotic are more difficult and expensive than those of other therapeutic fields, but the regulatory requirements, on the other hand, are the same. Recruitment of patients is difficult, rapid etiological diagnosis systems are scarce and only 14% of antibiotics subjected to phase 1 trials are commercialized.
• Production is also more expensive since the usual environmental problems are compounded by the need to avoid medium-environmental antibiotic pressure due to the waste generated.
• The treatments are not aimed at chronic patients and, on the other hand, should be restricted to the maximum to avoid the appearance of new resistance, which greatly limits the return on investment. Classical prescription incentive strategies and volume sales strategies should be avoided in the case of antibiotics.
• The antibiotics that we use daily in clinical practice, also used in animal health and in the agro-food industry, lose effectiveness quickly also limiting the useful life to recover the investment.
• The highest rates of multidrug resistance are concentrated in countries that don’t have the economic availability to pay for the investment, even though the globalization of health makes the risk of dissemination of resistance very high.

Therefore, it’s a failed model in which the bet is to invest more money than in other fields of therapy to market a product that will be used in the most restricted way possible and whose life will be shorter. You will agree with me that this is a "perfect storm" and that the model is doomed to failure in a sector such as the pharmaceutical industry accustomed to providing great benefits to its shareholders. To the difficulties for innovation is added the difficulty of maintaining the production of existing antibiotics, because companies no longer want to continue assuming the risks of an unsustainable model with the consequent risk of shortage of essential antibiotics.

In April 2014, the WHO declared antibiotic resistance as a serious global threat and in 2015 launched its Global Action Plan in the face of resistance (3). The problem has also escalated to the political and economic agenda. Leaders like Barack Obama or James Cameron have spoken publicly about the problem. At the last meeting of the World Economic Forum held in Davos, the first independent standard prepared by the Access to Medicine Foundation was presented on what different pharmaceutical companies are doing to combat resistance. The report quantifies by means of indicators what each company is doing not only in the field of research, but also in those of production, accessibility and promotion of the prudent use of antibiotics, and also points out the remaining potential that each one has to follow in order to carry on fighting the resistances:

If you are interested in the topic, watch the video of the press conference that took place in Davos in January of 2018.

The problem is complex and the solution requires public-private partnerships and innovative financing mechanisms. It’s necessary to have a system that dedicates public funds to reward those who investigate through a series of guaranteed payments at the time of the market launch of a new necessary antibiotic. These purchase agreements would not be related to the volume of antibiotics sold, but would be paid to recognize the companies' innovation by ending any commercial incentive to promote the use of large quantities of antibiotics.

The Innovative Medicines Initiative Joint Undertaking program has invested more than 660 million Euros with the aim of establishing collaborations between the European Commission and the European Federation of Pharmaceutical Industries. The New Drugs for Bad Bugs program aims to promote the fight against multi-resistance at all levels, from basic science, clinical development and the responsible use of antibiotics to new business models in a public-private initiative of a scale without precedents

However, as shown in a WHO report published in 2017 on antibacterial agents in development, progress is very slow (4). The authors state that the current pipeline could lead to 10 new products approved in the next five years, but these new drugs would not be a great innovation compared to the drugs currently available. Therapeutic options for most resistant bacteria are lacking, especially against gram-negative infections and multi-resistant tuberculosis.

Leaving exclusively in the hands of the market the innovation and the development of essential goods such as antibiotics is a recklessness that has led us to an emergency situation. The current model of drug research, as well as the establishment of the price we pay for them, is not based on the need or value they bring to society in terms of clinical benefit, but on the economic benefits they provide to shareholders of the companies. We should always keep it in mind.


Bibliography

1. Jim O’Neill, Chair. Tackling drug-resistant infections globally: Final report and recommendations. Review on antimicrobial resistance May0 2016. 
2. The Pew Charitable Trusts. A Scientific Roadmap for Antibiotic Discovery. Julio 2016.
3. Plan de acción mundial para las resistencias a los antimicrobianos. Geneva World Health Organization; 2016. ISBN 978 92 4 350976 1.
4. Antibacterial agents in clinical development: an analysis of the antibacterial clinical development pipeline, including tuberculosis. Geneva: World Health Organization; 2017 (WHO/EMP/IAU/2017.12). Licence: CC BY-NC-SA 3.0 IGO.