By the bioMerieux Connection Editors
In the 1980s, there were 18 major pharmaceutical companies developing antibiotics—at the end of 2019, there were three. One company, which declared bankruptcy in April 2019, had created a drug that the FDA deemed a “breakthrough therapy” and was added to the WHO’s list of essential medicines. The antibiotic could be a better therapy for CRE (Carbapenem-resistant Enterobacteriaceae, colloquially known as “nightmare bacteria”), in addition to treating other types of resistant infections. Another company, which declared bankruptcy at the end of 2019, manufactured four different antibiotics, one of which received FDA approval to treat drug-resistant pneumonia.
The value of antibiotics in modern medicine is indisputable—they have enabled complex surgeries and successfully treated infections that were death sentences less than a century ago. However, the development of drug resistance is inevitable, and antimicrobial resistance genes can be traced back thousands of years. We know that it’s necessary to innovate to stay ahead of resistance.
Given the dependence of modern medicine on antimicrobial drugs, and the inevitability of evolution, why is bringing a new antibiotic to market so difficult, and why are so many companies leaving the industry or going bankrupt?
Public Health Needs Don’t Align with Market Incentives for Antimicrobials
Medications that help manage chronic conditions, such as diabetes, do not face the same financial issues. Because patients typically require those drugs for longer periods of time, their need aligns with market incentives. As such, companies that research, develop, and manufacture them recoup investment costs rapidly and reliably. The opposite is often true for antimicrobials.
It takes an average of $2.6 billion to successfully develop and bring a new antimicrobial drug to market. But, because of the way that antibiotics are most often appropriately used—in short courses and infrequently on an individual patient—recouping the $2.6 billion investment is extremely difficult, especially in the short term.
Despite antimicrobials’ critical role in healthcare, companies often deem them too risky and unprofitable an investment to pursue. The precipitous decline and recent bankruptcies among companies researching and producing antimicrobials demonstrate that in dramatic fashion.
Patients Caught Between Distrust of the Pharmaceutical Industry and the Need for Antimicrobials
America’s relationship with pharmaceutical companies is complex. Many drugs, whether they are antibiotics or not, are lifesaving or life-extending therapies of great value. However, American patients face the highest prescription drug prices in the world, and not just for antibiotics. EpiPens, for example, cost around $50 per autoinjector up until 2007, when a company purchased the manufacturing rights and gradually raised the price to around $700 for a two-pack by 2016. In 2015, another company made headlines when it acquired the manufacturing license for a lifesaving antiparasitic drug and promptly raised its price from $13.50 to $750 per pill. And, multiple pharmaceutical companies have manufactured and marketed the drugs that directly resulted in the opioid crisis. Patients are understandably upset and distrustful of the pharmaceutical industry.
But that distrust doesn’t change the reality that many drugs, particularly antimicrobials, are critical for healthcare and patient survival. Nor does it affect the rising antimicrobial resistance we face around the world. If nothing is done to fight antimicrobial resistance, we are at risk of a global public health crisis of approximately 10 million deaths per year due to resistant infections. In addition to good stewardship practices, it’s clear that new antimicrobial drugs must be developed, and private enterprise is not able to fill the need under current market conditions.
Corporations, Organizations, and Governments Must Collaborate to Solve the Problem
Over the last few years, organizations around the world have researched ways to rescue antimicrobial drug development so that we do not face a shortfall of critical new treatments for infections. In 2017, the Transatlantic Task Force on Antimicrobial Resistance (TATFAR) released a report summarizing and comparing approaches recommended by a range of organizations and studies.
The report found three major areas of consensus:
- There is a need for a transparent, regularly updated, global antimicrobial resistance threat assessment process to track the development of resistance, monitor the effectiveness of existing antibiotics, and prioritize which new antimicrobial drugs should receive incentives.
- Multiple types of economic incentives will be needed to fully address all phases of drug development, comprising push and pull mechanisms.
- Nations must cooperate to develop, implement, and evaluate models that completely or partially de-link profits from volume of antimicrobials sold, accounting for both antimicrobial conservation and access.
The first item is necessary to ensure a logical, public-health centered approach to drug development, so that research and resources focus on the areas of greatest need. The second two items address the conditions that have led to a mismatch between public health needs and market incentives, driving pharmaceutical companies out of antimicrobial development or into bankruptcy. Organizations and studies have explored and recommended various ways to achieve the outcomes specified in items two and three, outlining the potential benefits and risks of each approach.
One of the recommendations the report discusses is altering incentives for antimicrobial drug development, specifically through adjustments to reimbursement from public insurers, such as Medicare and Medicaid. U.S. Congress has taken a preliminary step by proposing the DISARM Act, short for “Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms Act of 2019”. The Infectious Disease Society of American (IDSA), which provided guidance that informed the legislation, stated that, “Allowing for higher reimbursement for new antibiotics, requiring hospitals receiving increased payments for the drugs to monitor their use, report data to the U.S. Centers for Disease Control and Prevention, and establish stewardship programs, the DISARM Act reflects the value of safe, effective infection-fighting medicines to nation’s health.”
If passed, the DISARM Act would be a small but important step toward preventing a shortfall of new antibiotics. Further action, by governments, non-profit organizations, and companies worldwide, will ultimately be required to adequately address the issues surrounding new drug development and the threat of antimicrobial resistance.
Opinions expressed in this article are not necessarily those of bioMérieux, Inc.