Magazine Article | July 1, 2016

Administration's Response To Antibiotic Challenge Falls Far Short

Source: Life Science Leader

By John McManus, president and founder, The McManus Group

Public health advocates have been sounding the alarm bell for years that current antibiotic treatments and the limited few in development cannot address the rising crisis of drug-resistant superbugs. According to the Centers for Disease Control and Prevention, we are at a crisis point, with more than two million Americans annually being treated for infections that are resistant to antibiotics and more than 23,000 dying in the U.S. as a result.

But the recent finding of a Pennsylvania woman with a superbug carrying the plasmid-transferred MCR-1 gene — previously discovered in Chinese animals in 2015 and seen as unstoppable — caught the nation’s attention. MCR-1 is resistant to Colistin, an antibiotic of last resort, and its ability to jump from bacteria to bacteria can potentially result in widespread pan-resistant infections.

A key issue is proper stewardship of antibiotics — to ensure they are used judiciously and appropriately in order to slow the development of resistance. That’s clearly going to be a challenge as China alone used 12,000 metric tons of Colistin in farm animals in 2015, and only this year did India begin to limit OTC sales of antibiotics. But even if we eliminated all use of antibiotics in animals and all unnecessary use in humans, we still are bound by a pathetic pipeline to combat what we’re facing now.

Janet Woodcock, director of the FDA’s Center for Drug Evaluation and Research, testified on this crisis at the House Energy & Commerce Committee on June 14: “The decline in antibacterial drug research and development in the private sector, at a time when serious antibiotic-resistant infections are on the rise, is a very serious unmet medical need. … New antibacterial drugs are needed to provide treatment options in cases where resistance has eroded the effectiveness of existing drugs.”

Woodcock went on to observe the unique economic challenges impeding the development of new antibiotics: “Antibiotics are generally viewed as less profitable by companies and venture capitalists because of their relatively low price and because they are generally taken for a short period of time and often for only one course of treatment by any given patient. Compare this to the long, dependable income stream from a diabetes medicine or blood pressure medicine that patients often take for the rest of their lives or the relatively high price associated with cancer and some antiviral drugs.”

Despite this recognition of the market challenges, the administration appears to be focused solely on improved stewardship. On June 13, the Centers for Medicare and Medicaid Services (CMS) released a rather punitive proposal that would require hospitals to adopt strategies to curb overuse of antibiotics or risk expulsion from Medicare. Medicare already penalizes hospitals for patients who acquire infections during a hospital stay. But CMS argued the infection control rules had not been updated in 30 years, and the crisis requires more vigilant monitoring. The CDC found that only 40 percent of hospitals had an antibiotic oversight program in 2014.

This is all well and good, but how do policies focused on hospital compliance encourage development of new antimicrobials when the superbugs eventually overwhelm the current regimen? The administration offers no proposal in this area.

In September 2014, the President’s Council of Advisors on Science and Technology (PCAST) — a broad group of experts from academia, the hospital front lines, and industry — responded to President Obama’s request for “actionable” items to counter AMR (antimicrobial resistance), issuing an initial set of economic incentives, and finding generally: “PCAST believes that there is no way to sustain a robust pipeline of antibiotic development without a major influx of private investment. This will require substantially changing the economics of drug development.”

But none of PCAST’s recommendations made it into the President’s March 2015 Action Plan for Combating Antibiotic-Resistant Bacteria! What is the point of soliciting counsel from experts if their recommendations are summarily ignored?

Congress attempted to spur antibiotic innovation when it enacted the “GAIN Act” in 2012, with its minor incentives of priority review. Five new antibiotics have been approved since that time—only Avycaz (ceftazidime/avibactam) is considered of high value for unmet-medical-need gram-negative bacteria.

Policymakers still have not touched the fundamental market failure of antibiotics: very low price due to strong downward pressure from the array of generic antibiotics and reimbursement via low-paying inpatient payment schemes combined with deliberately limited volume of sales.

The politics and price of changing the economics of this market are not easy. PCAST found that annual investment of $800 million is necessary to average one new licensed antibiotic per year. The UK Review On AMR similarly recommended a global system of market entry awards in the amount of $800 million-$1.3 billion to develop unmet-need agents. So, to create an ongoing pipeline of these products will cost tens of billions. Some members of Congress are developing creative ideas to address these challenges.

Antibiotics are typically utilized by hospitals in an inpatient setting where reimbursement is controlled by predetermined payment bundles that do not account for the cost of innovative medicines. This incentivizes hospitals to utilize the cheapest drug, deterring use of loss-leading novel therapies. Medicare’s New Technology Add-On Payment (NTAP) program is supposed to provide additional reimbursement for innovative products that do not fit well under this capitated payment scheme, but only one antibiotic has qualified since the program’s inception in 2001. Moreover, NTAP covers only part of the acquisition cost of a qualifying drug and then for a temporary basis of two to three years.

Recognizing these deficiencies, Congressmen Roskam (R-IL) and Danny Davis (D-IL) introduced legislation that would fundamentally reform NTAP for antibiotics by paying hospitals the average sales price of those qualifying antibiotics that treat unmet medical needs, thereby eliminating cost from the clinical decision of the physician and hospital pharmacists. That bill passed the House of Representatives as part of the comprehensive CURES package but has not been taken up by the Senate yet.

Members on the Energy and Commerce Committee have considered enhancing the value of otherwise value-less antibiotics not by improving their reimbursement, volume, or IP protection, but by allowing the sponsor company to convey a period (say 12 months) of its own exclusivity to another drug product. The conveyance could be kept by the antibiotic innovator company or sold to another company entirely with unrelated but profitable products. This creative private-sector solution would inherently allow blockbusters for chronic diseases to fund antibiotic development where the economics are unlikely to ever be compelling otherwise.

Such a transfer policy has been supported anew by the UK Review On AMR and was supported by the otherwise ignored PCAST. The policy could be limited to products satisfying an unmet medical need and targeting high-risk pathogens.

No greater public health threat exists than the inability to treat infectious diseases—antibiotics are the backbone of modern medicine. The development of resistance is a process that cannot be stopped. Resistance arises through genetic evolution, and these new mutations can even be shared amongst bacteria. Without a constant stream of new products to maintain an advantage over these ever-changing pathogens, the future looks bleak. This requires a multiprong effort of improved stewardship and substantial investment in new innovation in pharmaceutical development through a variety of market incentives.

A recent article in The Economist stated, “Combining policies to accomplish many things at once demands political leadership, but recent global campaigns against HIV/AIDS and malaria show that it is possible. Enough time has been wasted issuing warnings about antibiotic resistance. The moment has come to do something about it.” Bingo!