TACKLING DRUG-RESISTANT INFECTIONS GLOBALLY FINAL REPORT AND RECOMMENDATIONS

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(FDCs), and then ensure an affordable, quality-assured global
supply of these through licensing mechanisms such as the MPP.
This type of proposal could do much on its own to reinvigorate
the TB pipeline if it were funded fully, but further consideration
should be given as to how it could be combined with a market
entry reward for a new TB regimen as an additional ‘pull’
mechanism. Subject to further exploration, we believe that the
system of market entry rewards that we propose for antibiotics
can play an important role in ‘supercharging’ the current TB
efforts, adding much-needed impetus to the work to bring TB
product development from the early stage to the point where
patients are treated. We view this as being possible in two ways:
• Market entry rewards should be payable to the developer
of a novel treatment regimen. A new monotherapy for TB
is of limited use in addressing global unmet need, and should
therefore not be rewarded by a market entry reward in the
same way that a conventional single antibiotic ought to be.
However, offering an appropriate market entry reward for a
complete regimen could provide extra impetus to regimen
development efforts supported by initiatives like ‘3Ps’ or
others. In principle, market entry rewards should be offered to
commercial and not-for-profit developers alike. When accruing
to not-for-profit developers they can be reinvested in public
heath oriented research.
• Market Entry Rewards can also be designed to entice
developers of antibiotics and alternative therapies for
infections other than TB to make their product available at
an early stage of development for testing as part of a TB
regimen. To do this, a premium could be awarded to product
developers who have supported TB regimen development
efforts by doing research themselves, making their antibiotic
available for exploration for possible action against TB at an
early stage, or making the product available for use in an FDC
through the type of licensing arrangements proposed by the
‘3Ps’ model.
Many details will no doubt need to be considered but the critical
message here is that tackling TB and drug-resistant TB must be
at the heart of any global action against AMR. The burden of TB
is too great, and the need for new treatments too urgent, for it
not to be a central consideration in the role and objectives of a
global intervention to support antibiotic development.
Better interventions to deal with E. coli
Of the 10 million people whom it is predicted may die from
drug-resistant infections each year by 2050, more than
three million will lose their lives to one bacterial infection:
drug-resistant E. coli. This would also account for more than
40 percent of the cumulative 100 trillion USD lost from world
production over the next 35 years. But the problem of drugresistant
E. coli is already manifest: carbapenem-resistant E.
coli more than doubled between 2008 and 2013 in the UK110.
Recent evidence suggests that colistin, the only drug that
works well against carbapenem-resistant infections, is also
starting to fail. Despite this, when we analysed the pipeline
for new drugs a year ago, only three drugs in the pipeline
appeared to have the potential to be effective against 90
percent of carbapenem-resistant E. coli infections.
In order to examine the benefits of tackling drug-resistant
E. coli we commissioned a piece of research from Professor
Neil Ferguson and Dr Pierre Nouvelle, from the NIHR Health
Protection Unit for Modelling Methodology at Imperial
College London111. As their business as usual scenario, they
examined what would happen if E. coli resistance in blood
stream infections increased to the current level of Klebsiella
pneumoniae (KP) over the next decade, as K. pneumoniae
and E. coli are very similar and K. pneumoniae has seen huge
increases in resistance over the past decade this seemed like
a realistic estimate for what could happen.
Using the above assumption, their work estimated that, by
2026 40,000 extra people would die from E. coli infections
annually in the EU alone, with an additional 1.7 million extra
hospital days. Nouvellet and Ferguson then modelled the
impact of a new diagnostic that could distinguish between
susceptible and resistant infections. They estimated that a
new diagnostic would save 6,000 lives and would reduce the
number of hospital days by more than 300,000 every year.
This is not only a huge decrease on the number of people
who would otherwise die from resistant infections, but it
is also likely to save health systems money in the longterm,
even accounting for the cost of the diagnostics. They
estimated that a new drug could save 7,300 lives. A new drug
and diagnostic combined would save an estimated almost
15,000 lives and reduce hospital bed days by 650,000.
110 Public Health England (PHE) voluntary laboratory surveillance
111 Nouvellet P, Robotham J, Naylor N, Woodford N, Ferguson N, Potential impact of
novel diagnostics and treatments on the burden of antibiotic resistant in
Escherichia coli, BioRxiv, 2016.