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There is a lack of push in the development of new antibiotics while anti-microbial resistance is a priority topic in healthcare policy and on the political agenda.
In a 2016 analysis of the deepening health threat posed by anti-microbial resistance (AMR), renowned economist Jim O’Neill predicted that by the year 2050, the number of deaths resulting from AMR will overtake those caused by cancer. Recommendations from O’Neill and his team on combatting the crisis were timely and aligned with governmental bodies, medical societies, health charities, and public health organizations. They include national and global awareness campaigns about the dangers of inappropriate use of antibiotics; incentives that encourage development of truly innovative antibiotics and new diagnostics; a focus on antibiotic stewardship across health settings; and a sharp reduction in the use of antibiotics in agriculture.
While AMR is a priority issue on the political agenda and in healthcare policy, there is a lack of tangible momentum in the development of new antibiotics. If you define a new class of antibiotics as one that hits a new target, there has not been a new class of antibiotic developed and marketed for nearly two decades. Instead, we have seen analogues of existing classes that, while being valuable additions in addressing some aspects of AMR, generally offer only incremental improvements over existing drugs.
A couple of decades ago, as AMR began to become a major issue, hospital antibiotic stewardship programs took a critical look at what drugs should be used, how quickly, and for which patients. As part of this process and with the rise in prominence of managed care, stewardship committees began to debate whether new antibiotics were worth the cost. Payers favored generics, and because the antibiotics were analogues developed in non-inferiority trials, drug companies often didn’t have the data to make an argument of sufficient differentiation in support of higher pricing for new therapies.
While blame for the malaise that has dogged antibiotic development can’t be attributed to a single source, the entire healthcare ecosystem now has a responsibility to pull together to deliver progress. International and governmental action and awareness-raising is to be applauded. However, the key to the revival of this sector and finding solutions to AMR lies in innovation: scientific, medical, marketing, financial, and regulatory.
In order to reintroduce innovation to antibiotic development to address the AMR crisis and generate profits to sustain the reinvigoration of the industry, “push” and “pull” initiatives have been instituted. Push incentives include public research funding, whereas examples of pull incentives are commercial enticements which better guarantee a return on the substantial investment required to bring a drug to market. Today, we are seeing some success with push incentives that provide funding for antibiotic discovery and development, but less progress with pull incentives that will help bring these new compounds to market.
The economics of bringing new compounds to market remain very challenging for investors, so many have shunned the space in favor of more profitable areas of drug development. The same is also true for the pharmaceutical industry-today, there are only two big companies still actively involved in antibiotic development. However, there are a number of smaller companies, including mine, working to develop completely new-mechanism, targeted antibiotics in areas of high medical need. If we can develop the agent so that it can demonstrate superior clinical outcomes for the patient, we can also drive down costs for governments and healthcare systems.
Prescribers may be unintentionally shutting down pathways to innovations that will help to bring new compounds to market and drive down costs. This is because doctors may have fallen into the habit of prescribing antibiotics, which may be inappropriate if the patient does not have a bacterial infection or if the antibiotic is of the wrong class for a particular infection. In addition, hospitals move slowly in reviewing treatment guidelines due in part to cost and pressure to keep antibiotics in reserve until they are needed. These guidelines are typically reviewed every five years, which is far too long for novel drugs to be introduced into the hospital system.
The healthcare system also needs to consider the long-term health economics of antibiotic prescription. Over the long-term, a more expensive antibiotic which provides superior clinical outcomes would be expected to save money for payers. For example, recurrence is the primary clinical issue in C. difficile infections (CDI), with up to 25% of CDI patients having a second episode. The risk of recurrence rises to 65% after a third episode and is typically associated with more severe disease and greater risk of death. Paying more for a new mechanism antibiotic upfront makes sense if it can improve patient cure rates and lead to a reduction in the burden on healthcare systems and the associated expense further down the line.
Importantly, there are scientific advances that are making the discovery of targeted antibiotics possible. For instance, genetic modification and next-generation sequencing of bacteria have accelerated drug discovery. This progress, coupled with the development of rapid diagnostics to identify the bacterial cause of an infection, mean that highly targeted, new-mechanism drugs could be available to kill specific bacteria, providing new front-line therapies for patients. Existing broad spectrum agents can then be reserved for difficult cases. This could also result in a reduction in AMR.
After more than twenty years of sparse development, we’re at a critical juncture. Push and pull incentives are required and the industry needs to demonstrate how innovation in antibiotic development will lead to patient benefit and economic reward. Failure to do so will see those researchers and executives with significant antibiotic development experience and expertise lost forever. If we, as an industry, don’t prioritize innovation, society as a whole will suffer. We have a unique opportunity to revive the engine room of antibiotic development to bring wider medical and societal benefits-let’s not miss it.
David Roblin, MD, is the Chief Medical Officer and President of Research and Development at Summit Therapeutics.