Though international focus is turning to antimicrobial resistance and incentives are being provided for research into new drugs, there are many hurdles to be jumped before a blockbuster can be discovered and developed in this challenging field, says Christophe Homer.
With UK Prime Minister David Cameron talking of a return to the “dark ages” and Professor Sally Davies, the UK Chief Medical Officer, speaking of “the apocalypse”, 2014 was the year where antibiotics and the threat of antimicrobial resistance (AMR) became a hot topic in the mainstream media. While this has been a growing discussion point for some time in the healthcare, scientific and pharma communities, the general public face the very real prospect of drugs widely relied on in day-to-day use and routine medical procedures no longer being able to cure simple bacterial infections.
How can this be prevented?
AMR is a complex, global issue and corrective action is only possible if we accurately know and understand what is happening, where and why, at every level. To this end, the World Health Organisation (WHO) has been monitoring the situation for over two decades and publishing numerous reports and guidelines, the latest being Antimicrobial Resistance – Global Report on Surveillance 2014.
Armed with this understanding, the following issues can be more effectively addressed:
1. Prevent the need for antibiotics. Immunisation programmes engender immunity and make people less susceptible to pathogens. Implementing educational programmes that promote better hygiene and sanitation at a global level, but especially for developing countries, automatically reduces incidences of bacterial infection.
2. Prevent the misuse of antibiotics at all levels. Likewise, increased education needs to be introduced at an individual patient and health care professional (HCP) level, but should also be a national government/health policy. Antibiotics are also used in agriculture and livestock food production, which can facilitate resistance and is a sector that requires great scrutiny. Further to education, international government agreements are required that set standards/targets for monitoring and reducing antibiotic use, much as has been seen with CO2 emissions.
3. Accurate use of the correct antibiotic. When antibiotic use is necessary, a more personalised approach is needed, whereby the specific strain of pathogen is identified and the most appropriate antibiotic is administered.
4. Development of new drugs. While the above steps will go a considerable way to dealing with AMR as a whole, there is still an urgent need for new and effective treatments.
Challenges of antibiotic development
There have been few new classes of antibacterial discovered in the last 30 years, although the recent publication in Nature on the discovery of teixobactin may prove to be a ‘game changer’. So, if the need for new antibiotics has been widely recognised for so long, why has big pharma not provided the breakthrough?
While the obvious solution would be to invest more in research to discover new antimicrobials, the reality is that this is as challenging scientifically as it is unrewarding economically. Even leaving aside the prohibitive cost of bringing an antimicrobial to market – thought to be upwards of £750 million – antibiotics have become less and less attractive for big pharma for a variety of reasons. First, bacterial infections tend to be short term, hence they are much less profitable than chronic illnesses where medication needs to be taken for life.
The mature nature of the market means the majority of drugs are cheap-to-produce generics, which would make it difficult for a new drug to be seen as cost effective
Further, the mature nature of the market means the majority of drugs are cheap-to-produce generics which would make it difficult for a new drug to be seen as cost effective. The recent economic climate has made many companies more risk averse and, as any new blockbuster antibiotic faces the prospect of resistance developing and the possibility of guidelines which restrict its use, it is no wonder pharma companies have been reluctant to invest. Without greater financial incentives to tempt big pharma to start investing more heavily in antibiotics research, such as extending patents or guaranteed returns on investment, it is hard to see where new drug breakthroughs will come from.
Academia, university spin-offs and small start-ups are the best hope – an approach which complements the acquisition pipeline model currently operated by many pharma companies since the financial downturn. This allows others to assume the inherent risks of early-stage R&D and big pharma to leverage their know-how and infrastructure to bring to market those molecules that do have promise. Plus, recent financial incentives have been encouraging these smaller players, as exemplified by the £10 million 2014 Longitude Prize.
What form might these new breakthroughs take?
The mainstay of recent endeavours has been to genetically engineer existing products so that they are slightly different in order to circumvent resistance mechanisms and, while the returns are likely to be small, it is a relatively safer and easier approach. Another angle is the development of small molecules that can be administered in conjunction with antimicrobials to prevent resistance mechanisms such as efflux. In the area of personalised medicine, work is ongoing to develop quick and simple tests to identify the strain of bacteria.
But the biggest reward remains the discovery of a new class of antibiotic, which is most likely to come from as yet undiscovered strains of bacteria, from rainforests or even the soil beneath our feet. Even when found, any bacteria must be able to be cultured and tested against known pathogens to determine the extent of any antibiotic properties. And, after all this, it still has to be tested for safe use in humans and be cost effective to produce.
So what is the answer?
Bacterial infection has no political allegiance, no geographic limit and is indiscriminate and merciless in its own pursuit for survival. AMR must be kept at bay! Only by working together and taking responsibility at patient, HCP, pharma company, national and international government levels, can we maintain the low rates of mortality related to bacterial infection that we have become so accustomed to and complacent about.