The decision by US Congressional leaders to remove the Developing an Innovative Solution for Antimicrobial Resistant Microorganisms (DISARM) Act from the recent Coronavirus Aid, Relief, and Economic Security (CARES) Act represents an alarming failure.
This action fails to recognize, validate and address the structural impediments to the development of life-saving antibiotics that must play a critical role in the current coronavirus pandemic, as well as potentially prevent a future crisis.
The DISARM Act updates the dysfunctional reimbursement system for important new antibiotics and represents a critically important legislative solution to support an effective end-to-end pandemic response across the entire infectious diseases sector.
Today’s COVID-19 crisis is due to the nature of this pathogen and a result of inadequate pandemic preparedness. The current crisis is a sobering reminder that viral and bacterial superbug pandemics are an integral part of human history. Future pandemics are inevitable; and, because it is very clear that potentially lethal secondary bacterial infections accompany viral infections such as COVID-19, we will continue to need effective and safe antibiotics that address today’s antimicrobial resistance (AMR) landscape.
Over the 5-year period contemplated, DISARM would have represented less than 1% of the $2tn in CARES, but would have delivered an incalculable benefit in terms of lives saved, both today and in the future. DISARM would have refashioned an antiquated payer system into one that recognizes and rewards innovation in antibiotics development. By cutting DISARM from CARES, Congress has demonstrated an inability to connect the dots on how legislative policies could support the antibiotics marketplace by moving the payer system in a sensible direction that recognizes the value of innovation and the life-saving properties of all antibiotics.
Congress’ action to actively remove DISARM from the CARES Act also represents its failure to recognize the importance of having a robust and secure foundation for the development and commercialization of new antibiotics now and in the future. This point is crucial because we are falling behind the innovation curve in our never-ending battle against bacteria: even as the prevalence of drug-resistant bacteria continues to grow, the pipeline of promising new antibiotics is drying up. This will be associated with a predictable increase in mortality of Americans as the “pre-penicillin era” will have arrived.
Antibiotic biotech companies are going bankrupt at historic rates, in large part due to the glacial pace of updates to clinical guidelines, policies on use that prioritize cost over saving lives and a reimbursement system that actively discourages the appropriate use of new antibiotics for almost 20 years. By failing to support DISARM, Congress has chosen to put at risk the health of all Americans who develop COVID-19, as well as endanger the lives of future generations. Bacteria are blind to politics.
Context: Present And Past
Antibiotics are essential as part of the end-to-end resources needed to address the COVID-19 pandemic as well as to protect people from future infectious disease pandemics. From our experience with recent viral pandemics – H1N1, MERS, SERS and even the 1918-1919 influenza pandemic – we know that secondary bacterial infections are major contributors to the severity and morbidity and mortality seen with these infections. In the face of viral pandemics, antibiotics undoubtedly save lives. But today’s antibiotic resistance environment complicates the treatment requirements of many viral infections and COVID-19 is no different. Secondary bacterial infections as well as multidrug resistant pathogens have been identified in patients with COVID-19 and it is well known that infections caused by resistant pathogens are associated with significant morbidity and mortality.
Unfortunately, the existing reimbursement system encourages the use of the least expensive antibiotics, which results in patients today receiving antibiotics that are often less effective and less safe than newly approved antibiotics. This leads to poorer outcomes, increased mortality and serves as a stark reminder that we do not have enough effective antibiotics – let alone enough new ones – to fight these secondary bacterial infections that accompany a viral pandemic.
We must also remember that pandemics are not just viral; some of the largest and most devastating plagues in human history have been bacterial. For example, the bubonic plague or “Black Death” of the 1300s. Our next pandemic after COVID-19 could be bacterial instead of viral. Either way, if our antibiotic sector is gone, who is going to make the antibiotics we need? It is massively naive to think these products just turn up overnight; we have to develop them well ahead of time. To borrow an analogy from antibiotic R&D expert John Rex, antibiotics are like fire extinguishers or vehicle breakdown memberships: you do not need them until you actually need them, and you do not know when that will be.
Congress could have helped us prepare for the next pandemic by including DISARM in CARES; instead it has failed to be decisive and forward-thinking.
It is wrong for Congress to consider DISARM a handout. Even if DISARM were in place, a company would still have to prove itself by discovering and developing a new antibiotic, getting funding to move the product through clinical trials, regulatory review and approvals, then launch it into the marketplace. It took Paratek Pharmaceuticals Inc. over 20 years to develop and commercialize Nuzyra (omadacycline)
The need for new antibiotics investment is real and it is urgent, yet the marketplace is fragile and failing. Many of the companies that make antibiotics today are either exiting the field (Octagon Therapeutics Inc.), struggling on the brink of financial collapse or have already gone bankrupt (Achaogen Inc., Melinta Therapeutics Inc., MotifBio and Tetraphase Pharmaceuticals Inc.), and no doubt we will see more go under in the next six to twelve months. Government support and leadership focused on updating the current reimbursement system is needed urgently.
Trading Away The Future
Of course, reimbursement is not the only source of post-market revenues for an antibiotics company. Paratek’s public-private partnership (PPP) with the Biomedical Advanced Research And Development Authority (BARDA), announced in December 2019, is an example of an alternative option. Under the BARDA contract, which is valued at up to $285m over five years, Paratek will develop Nuzyra as a treatment for pulmonary anthrax, fund all FDA post-marketing requirements associated with the drug’s initial approval, and enable procurement of up to 10,000 60-day treatment courses for the Strategic National Stockpile. The contract also provides $20m to bring the company’s supply chain fully onto US. soil – from API to final drug product. BARDA initiated the onshoring step on 1 April, three months earlier than originally planned.
BARDA would not have done this deal with Paratek, and provided $20m for onshoring, unless it believed that Paratek had long-term viability and growth potential. Future BARDA antibiotics public-private partnerships will be with companies that have a strong balance sheet and future growth potential beyond their first approved product. But there will not be any such companies if the antibiotics sector continues to falter or disappears entirely.
BARDA is not the only solution and BARDA cannot fix the antibiotics sector, one company at a time. There must be an overarching government policy that accelerates the development of new antibiotics by changing a reimbursement system that impedes the survival of companies once their products are approved.
CMS should revise the Diagnostic Related Grouping (DRG), under its authority, to create an antibiotics carve-out by putting a rule into the inpatient prospective payment system (IPPS). Without legislative “cover” for CMS to make the revisions, it appears that it may just be business as usual – and in time, everyone in the US and the world will be without safe and effective antibiotics to combat deadly and resistant bacterial infections. To avoid that nightmare scenario, the government must step up to initiate change.
These are extraordinary times. The full impact of the current COVID-19 pandemic on the health of the US is yet to be determined; future pandemics could be even worse. The US government’s response to the next pandemic may well require a stimulus package much larger than DISARM because Congress chose, today, not to make a critically important and pragmatic investment to support innovative antimicrobial development and commercialization. Legislators have traded away our future well-being for modest savings in the present.
The Antimicrobials Working Group of biotech companies, which are focused on the development of innovative antimicrobials, remain committed to developing lifesaving therapies that will bolster our ability to battle pandemics like COVID-19. It is imperative that Congress act immediately to pass legislation that supports those efforts.
About The Author: Evan Loh, MD, has been CEO of Paratek since June 2019. Prior to that, Loh was chief operating officer. Previously, he served as senior vice president, development and strategic operations, worldwide R&D at Pfizer.