The increasing prevalence of antimicrobial resistance (AMR) jeopardises the efficacy of existing life-saving antibiotics, as we explained in our previous article in this series. The problem is compounded by the lack of development of new antibiotic classes in the pharmaceutical sector. In this article, we will explore the reasons for this pipeline problem, as well as potential solutions.
No major new class of antibiotics has been discovered since 1987 and too few antibacterial agents are in development to meet the challenge of multi-resistant bacteria. According to the World Health Organization (WHO), of the 50 new antibiotics in clinical development, few are considered innovative enough to add significant value to the current pool of antibiotics.
Given the discovery void since the late 1980s, the pharmaceutical industry needs to accelerate its R&D efforts to develop new antibiotic classes and keep pace with the evolution of multi-resistant bacteria. There will be a great human and financial cost if this does not occur. According to the WHO, there are few potential treatment options for those multi-resistant bacteria identified as posing the greatest threat to health. Without effective antimicrobials for prevention and treatment of infections, medical procedures such as organ transplantation, cancer chemotherapy, diabetes management and major surgery (for example, caesarean sections or hip replacements) become very high risk. Furthermore, AMR increases the cost of healthcare due to longer stays in hospital and the fact that more intensive care is required.
Currently, pharmaceutical companies are struggling to make a commercial case for investing in antibiotics. It is difficult to recoup the R&D costs due to the high cost of development, the low sales price of antibiotics compared with other drugs, and the fact that resistance development can happen quickly, impacting usability and long-term sales. Also, returns on investment will be limited because of restrictions in the use of the newly developed antibiotic to preserve efficacy. While pharmaceutical companies are traditionally paid based on the volume of the product sold, governments and other key stakeholders are trying to reduce antibiotic use.
In the face of a growing AMR threat, we need to stimulate more research into new antibiotic classes. This will require more partnerships and cooperation among policymakers, academics and the pharmaceutical industry in order to address the scientific, regulatory and economic challenges. It should also involve commercial incentives, which would need to be beneficial for society and provide a reasonable return on investment for pharmaceutical companies. There is some positive momentum in these areas, for example:
- As part of a Global Action Plan on Antimicrobial Resistance, the WHO and the Drugs for Neglected Diseases initiative jointly launched the Global Antibiotic Research and Development Partnership. This encourages R&D through public-private partnerships. By 2023, the goal is to develop and deliver up to four new treatments by improving existing antibiotics and accelerating the entry of new antibiotic drugs.
- The United States has enacted a law to stimulate the development of new antibiotics. The law increases the commercial value of antibiotics that are intended for serious or life-threatening infections by extending the period for which the drugs can be sold without competition from generic drugs by five years. New drugs that could benefit from this law are now in the antibiotic pipeline. The UK government is testing a ‘subscription’ style model that pays pharmaceutical companies upfront for access to drugs based on their usefulness to the NHS.
- In July 2020, more than 20 biopharmaceutical companies announced their participation in the industry-led AMR Action Fund, which will support the research of new antibiotics. It pledges to invest US$1bn with the aim of bringing two to four novel antibiotics to market by 2030. The initiative also commits to creating shared technical resources and enabling co-operation across supporters’ research efforts in order to streamline the development process and reduce the cost of the clinical development of new drugs.
We know it is not enough to develop new antibiotics. Responsible and robust manufacturing, sales and use practices must also be in place to slow the development of AMR, which we address through our engagement with companies.
We engage with pharmaceutical companies on how their R&D strategies address this public health threat, whether responsible sales practices are in place, and how effluence at production sites is managed to ensure that antibiotics do not enter the environment. We ask companies to assess and acknowledge the risk of AMR to their business. We expect companies to support partnerships and advocacy campaigns that encourage public policy solutions. In the next article in this series, we will discuss our engagement on pharmaceutical companies’ responses to the current pandemic.
We appreciate that the development of new antibiotics will not alone counteract the challenges posed by AMR, as AMR is a natural and continuous selection process that occurs when antibiotics are used. Existing and new antibiotics will need to be used more sparingly through effective antibiotic stewardship. However, we need more innovation in this field, as well as in vaccine development and diagnostics. This will require a concerted, global effort to accelerate the pace of pharmaceutical R&D.