most in need, they must be embedded in clinics throughout the world. 6. Promote the development and use of vaccines and alternatives. Some progress is being made, but the absence of enough interest by big pharmaceuti- cal companies and the lack of market entry rewards, will slow this important area. 7. Improve the numbers, pay and recognition of people working in infectious disease. Following the increase in AMR publicity and financing, the num- ber of researchers in the area seem to be increasing. 8. Establish a Global Innovation Fund for early- stage and non-commercial research. The news is encouraging because the financing for early stage research and development is increasing. For exam- ple, the Chinese and British governments, the Wellcome Trust and the US Biomedical Advanced Research and Development Authority (BARDA) and the Danish pharma company Novo have announced significant new joint funding initia- tives. 9. Better incentives to promote investment for new drugs and improving existing ones. Although rep- resentatives of the 25 largest pharmaceutical com- panies are thought to have discussed AMR (at Davos 2018), they agreed to remain engaged on the issue. This is very disappointing. For example, serious interest in AMR by big pharma and market entry rewards, as suggested by the O’Neill report would stimulate and facilitate new drugs, vaccines and diagnostic tests. 10. Build a global coalition for real action-via the G20 and the UN. Progress is slow. On the one hand, governments tend to move slowly. On the other, if all the people who die from AMR in one year were to die in one day (for example in plane crashes or fires), governments would move much faster than they have done over the past two years. Overall, progress during the past two years has been patchy. Some areas, such as the return of big pharmaceutical companies and the introduction of market entry rewards have not occurred. This means that new drugs, vaccines and diagnostic tests will struggle in the development and market- ing stages. In my view, at the present slow rate of progress, the O’Neill projections for 10 million deaths per year by 2050 may be an underestimate.

Universal access- – supply to the rich and to the poor Antibiotics are life-saving drugs. Antimicrobial resistance means that many antibiotics are no longer effective amongst the poor. New antibiotics are going to be discovered and developed mainly in high-income countries, such as the US. But most of


the burden of AMR disease is already falling upon lower income countries, and will continue to do so. In the 1980s, new drugs for AIDS were developed in high income countries, but were too expensive for the poor. Indian companies such as Cipla, led by Yusuf Hamied, produced AIDS drugs which were affordable by the poor for a fraction of the cost. This is a somewhat extreme commercial model. In the AMR field, there is a not-for-profit model, called the Global Antibiotic Research and Development Partnership (GARDP). WHO was the midwife, DNDi the mother and GARDP the baby, born in 2016. It has a remit to ensuring uni- versal access. In addition, GARDP aims to develop antibiotics and antibiotic combinations which are not commercially viable, such as treatments for sepsis in babies and children, and for highly-resis- tant gonococcal infection. This model is not suit- able for commercial development, although GARDP does partner with companies. An example of a commercial model (there are many) is Helperby Therapeutics which has a partner in India which co-develops combinations of antibi- otics and supplies to India and Africa at prices which are affordable by the poor, while Helperby sells into high income countries.

Stewardship Antibiotic stewardship is co-ordinated intervention which reduces inappropriate use of antibiotics by helping the selection of the optimal antibiotic regi- men (the dose, duration and route). The global reduction of inappropriate antibiotic use is impor- tant because the administration of an oral antibiot- ic to humans results in antibiotic resistance in the large intestine within seven days. The length of time that the resistant bacteria are detectable in the individual is up to one year. This means that each individual who has been treated with an oral antibiotic is defaecating resistant bacteria for up to a year. Since many people in low income countries do not have access to toilets, contamination of the environment with highly-resistant bacteria occurs. It has even been recorded that up to half of visitors from a low-level resistance country who spend time in a country with a high level of antibiotic resistance, return home carrying highly-resistant bacteria in their large intestine. In high-income countries, where water flushing toilets are usually available, the antibiotic treated individual carries resistant bacteria in the intestine, may transmit them to their household and may be a risk to them- selves – for example, if they require surgery or become immunosuppressed. Furthermore, sewage systems sometimes break down and release raw

Drug Discovery World Summer 2018

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