MCDONALD: Trying to GAIN an edge on ‘superbugs’

During a hockey game last Saturday, the Boston Bruins defenseman, Dennis Seidenberg, took a skate blade to his leg, slicing it open. By Thursday, the cut was infected, sidelining Seidenberg, who was now on a course of antibiotics. Three days later, Seidenberg was good as new, even scoring a goal in a win over the New York Rangers.

But imagine if the antibiotics hadn’t worked — if the bacteria infecting Seidenberg’s wound kept right on multiplying despite being plied with drug after drug. Seidenberg would be lucky to survive, and almost certainly would no longer play for the NHL. The scenario, while morbid, isn’t all that far-fetched given the increase in infections with drug resistant bacteria, or ‘superbugs,’ and the slowing trickle of new antibiotics being developed to fight them.

The Center for Disease Control estimates that 100,000 people die from hospital-acquired infections per year — many of them resistant to at least one drug — like methicillin-resistant Staphylococcus aureus (MRSA), or vancomycin-resistant Enterococci (WRE). A piddling two new antibiotics were approved between 2008-2011.

The problem is both a scientific and economic one. We need creative thinkers to design drugs that halt nasty microbes in new ways, especially for hardy gram-negative bacteria, like Klebsiella pneumoniae. Gram-negative bacteria have an extra outer membrane that can act as an endotoxin and is also pretty darn good at preventing most antibiotics from getting inside to disrupt their basic structure. Often, the only remaining antibiotics that work for many drug-resistant gram-negative infections are holdovers from the 1940s that are also fairly toxic to patients. Resistance to even these rarely used older antibiotics is also spreading, meaning patients aren’t even given the choice between risking kidney failure and dying from an infection — there simply are no existing antibiotics to cure them.

But few pharmaceutical companies are filling the demand for new antibiotics, which won’t command the high returns of decades-long daily lifestyle drugs, such as cholesterol-lowering medications. How are companies expected to recoup a $1 billion investment on a new antibiotic that when used properly will be taken in short bursts and used sparingly?

Legislators decided to remedy the situation by trying to correct the market imbalance, and make it more attractive for pharmaceutical companies to finance the development of novel antibiotics. Last June, the Generating Antibiotic Incentives Now (GAIN) Act was introduced to the House of Representatives, and in October, Senators Richard Blumenthal (D-CT) and Bob Corker (R-TN) introduced the companion bill in the Senate.

The GAIN Act shifts the calculus slightly: it provides an extra five years of patent exclusivity for the new drug, with an extra six months on top of that if a diagnostic is also developed. The Act also intends to lessen hardship for companies during the approval process by promising a fast-tracked review, and more vaguely, requires a review of the guidelines for the clinical trials.

Since any important drugs are going to be fast-tracked anyway, the bolus of the bill is the exclusivity extension. The main question is whether five extra years before going to generic is enough of a bonus to motivate companies to commit to some serious bacterial ass-kicking. Pfizer and Johnson & Johnson, the two largest pharmaceutical companies, dropped their antibiotic divisions in 2011, leaving antibiotic innovation for the smaller companies (often start-ups) that have already committed to the niche. Thus, while the GAIN Act has high aspirations, it’s debatable whether the economic incentives are pushing any businesses toward antibiotic R&D or are merely increasing the bottom line of those already pursuing it. Nonetheless, it’s important for the government to recognize that resistant bacteria are a serious health threat that cannot be solved on its own with just patient education and careful conservation of our current antibiotics.

Last Thursday, after little action in Congress on the Act for many months, a senate committee included the GAIN Act in a discussion draft of a bill that changes how the Food and Drug Administration would regulate medical devices. It remains to be seen whether or not it will stay there, but it’s clear Blumenthal won’t let the legislation die without a fight. Blumenthal will be in New Haven this Thursday to discuss the GAIN Act along with Thomas Steitz, Yale’s own Nobel Laureate, and several higher-ups of Cubist Pharmaceuticals, a small Massachusetts-based company that bills itself as the “go-to folks for new acute care therapies.”

Since the development of mass antibiotics following World War II, Americans have learned to take these miracle drugs for granted. In the years to come, we’ll no doubt have a superior Siri on our iPhones ready to decipher our every command, but we may not have something as simple as effective antibiotics. Congress, let’s pass the GAIN Act, but please, don’t stop there.

Jessica McDonald is a sixth-year graduate student in the Department of Immunology. Contact her at jessica.mcdonald@yale.edu.

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