Antibiotic drug research and developmentBMJ 2012; 344 doi: http://dx.doi.org/10.1136/bmj.e2591 (Published 11 April 2012) Cite this as: BMJ 2012;344:e2591
- Jean-Pierre Paccaud, director of business development
Two linked articles highlight two very good reasons for international health authorities and governments to be seriously worried about the emergence of antimicrobial resistance: the worldwide spread of multidrug resistant bacterial strains (doi:10.1136/bmj.e1567) and the paucity of antibacterial compounds currently being researched (doi:10.1136/bmj.e1782).1 2
As antimicrobial resistance spreads worldwide and increasingly affects patients with very little buying power, traditional market forces will no longer provide the antibiotics that the world badly needs. The World Health Organization recently published a thoughtful analysis of the situation, along with measures that should be taken to face the threat.3 However, no clear way of increasing new antibiotic research and development has emerged.
The development of antibiotics has been increasingly challenging in recent years. Despite tremendous advances in the biological sciences, the difficulty in identifying new mechanisms to kill human bacterial pathogens has discouraged the few companies that are still active in the field. Clearly, we can no longer rely on direct competition between private companies alone to drive the emergence of new drugs.
So and colleagues propose sharing the risks of the antibiotic drug development process by spreading the burden across all stakeholders, from academia to the private sector, as a potential answer to the current crisis.2 Such broad sharing of resources, competences, and information should promote innovative approaches and a paradigm shift away from conventional methods of identifying antibacterial agents (via standard “Petri dish” assays or target based approaches) to exploring new ways to fight bacterial infections, such as by working on host-pathogen interactions, disrupting bacterial adaptability to the human host, or targeting latent bacteria. Microbiologists and clinicians, many of whom still take the view that “a good bug is a dead bug,” may be challenged, as will regulators who will have to move out of their “confidence zone.” However, past failure shows that we urgently need to step outside of traditional approaches.
Several “push” and “pull” mechanisms have been proposed to incentivise the private sector to invest in antibiotic development in response to the obvious failure of market forces to do so. However, such mechanisms alone are unlikely to incentivise drug companies to commit to the large investments needed to develop a new antibiotic, given the high risks of failure and the small return on investment.
Pull mechanisms, such as the bill to be presented to the US State Congress known as GAIN (Generating Antibiotic Incentives Now) can even be deleterious in the long term. This bill proposes to grant extended data exclusivity to companies that bring new antibiotics to market, as well as to prompt the Food and Drug Administration to review its guidelines for clinical trials of antibiotics. If the last measure is justified and needed, then extended market protection unfortunately goes in the wrong direction. Such actions would further strengthen the link between sales and revenues, a key factor that underpins aggressive promotion of a new antibiotic and its inevitable misuse. The bill does not provide guidelines on pricing (with consideration of the accessibility of new drugs in developing countries) or on the conservation (limited use) of any new antibiotic. Moreover, the proposed mechanisms are unlikely to motivate the private sector, given the still modest pricing of antibiotics compared with drugs directed at chronic and lifestyle diseases.4
In contrast, push mechanisms such as research grants, subsidies, dedicated funds, and tax credits can be helpful in the early discovery stage. They will not, however, stimulate necessary translational research and clinical development unless strong additional mechanisms are put in place to ensure drug development.
If the private sector is ill equipped to take up the challenge for economic reasons and the anti-infective community reluctant to embrace innovative approaches, who will develop the next generations of antibiotics? We must continue to invest heavily in research to ensure a renewable pipeline of products because any new antibiotic may eventually become obsolete. The market life of antibiotics is often short as bacteria become resistant despite preventive measures. It is thus reasonable that antibiotic development should be the responsibility of the public sector. Such a responsibility would mean that new antibiotics, the necessary tools to fight antimicrobial resistance in the long term, might be regarded as public goods. New antibiotics would then benefit not only a fortunate few but might be made available to every patient in need, whether from developed or developing countries, at an affordable price. The public sector could share the risks of drug development through funding, as suggested by So and colleagues,2 and also the reward for success: bringing affordable antibiotics to the population.
Strong financial support for drug research and development from the public sector is key to driving true innovation because it would delink investment from the need to deliver financial returns, which is impossible in the private sector. Some have suggested the creation of an “International Fund for Antibiotic Research” financed by governments (in the model of the Global Fund), and coordination of research and development by product development partnerships. Such partnerships have been successful in developing new treatments for neglected tropical diseases, substituting efficiently for the private sector where market incentives have not driven research and development, and at very low costs. For example, the Drugs for Neglected Diseases initiative developed five new treatments for malaria, sleeping sickness, leishmaniasis, and Chagas’ disease over seven years, with about €100m (£83m; $131m). Other partnerships, such as the Medicines for Malaria Venture, have also delivered innovative products in a cost efficient manner. Product development partnerships could provide a realistic way to engage into innovative antibacterial research and development by coordinating the resources, skills, and efforts of all current players (from academia to drug companies) while absorbing the risks inherent in drug development. Eventually, industry could be responsible for manufacturing and distributing the products, at a price that ensures the sustainability of production and distribution but that does not include research and development costs, which will have been financed through the public sector.
The battle against antimicrobial resistance requires innovative approaches, because new resistance will continuously emerge, and sustained efforts are needed to produce new antibiotics, to control their usage, and to ensure that every patient will have access to these life saving drugs.
Cite this as: BMJ 2012;344:e2591
Competing interests: The author has completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declares: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.
Provenance and peer review: Commissioned; not externally peer reviewed.