illustration by Marcos Chin

illustration by Marcos Chin

It’s hard to overstate the impact that antibiotics had on medicine after they became widely available in the 1940s. In the United States, the leading causes of death shifted from infectious to noncommunicable diseases such as heart conditions and cancer. Antibiotics helped lift the average life expectancy at birth from 54 years in 1920 to 78.6 today. But almost as soon as the treatments were made available, physicians had to cope with the specter of antibiotic resistance, a fight that has become increasingly desperate in recent years with the rise of antibiotic-resistant superbugs.

“We are approaching a cliff,” says Anna Diaz Triola (MBA 2000), vice president of marketing at Summit Therapeutics in Cambridge, Massachusetts, which is part of a cohort of small pharma companies that, against the odds, are trying to turn the superbug tide. “If we don’t take steps to slow down or stop drug resistance, we will fall back to a time when simple infections killed people. Can you imagine? That’s a bit of a doomsday perspective, but it’s a call to action.”

The World Health Organization echoes Triola’s sense of urgency, warning that antibiotic resistance presents one of the greatest threats to health, food security, and development worldwide. And according to the Centers for Disease Control and Prevention, each year in the United States at least 2 million people get an antibiotic-resistant infection, and at least 23,000 people die as a result. And yet, there are only 42 antibiotics currently in clinical development, and typically only 20 percent of infectious disease drugs that enter phase 1 clinical trials will receive FDA approval.

Eric Kimble (MBA 1994), chief commercial officer at Entasis Therapeutics in Waltham, Massachusetts, suggests two main reasons why so few new antibiotics are in the pipeline. First, antibiotics are used for relatively short courses and, as a result, aren’t as profitable as chronic-care medicines. Second, in the United States, hospitals budget for all the drugs used in a facility, and new antibiotics—which are priced higher than their older counterparts to recoup development costs—have to compete for a share of that finite budget.

In recent years, many large pharma companies have stopped their antibiotic research altogether, with small pharma trying to fill the void—often unsuccessfully. Kimble points to San Francisco–based Achaogen, which filed for bankruptcy last April despite securing regulatory approval for one of its antibiotic treatments in 2018.

Given the catch-22s of making a profit on antibiotics, what’s a pharma startup to do? Begin with the pharmacoeconomic data, Kimble says: “We need to justify the higher prices of our drugs, and we need to do a better job of helping hospitals understand that by using a more extensive antibiotic up front compared to the older generic version that has some resistance, we are saving those institutions money [by ensuring], for example, fewer days in the hospital.” Triola echoes this argument. “Without any economic data to justify the use of premium-priced treatments over cheaper generics, how are you going to make the case that a hospital system should spend dollars on a branded agent against pennies of a generic agent?”

Small pharma can also focus on one bug at a time instead of broad-spectrum drugs that attack whole swaths of them, potentially fostering resistance. For example, one drug in Entasis’s pipeline fights Acinetobacter baumannii, a lethal bug that tends to travel down endotracheal tubes and often causes pneumonia in ICU patients. When the drug goes to market, the company plans to have data to back up its price. “If we say, for instance, that we can wean a patient off a ventilator three days sooner…and we get a patient out of the ICU four days sooner...then that’s a justified cost savings to the hospital, which we can then use to price our drug appropriately,” Kimble says.

Kimble and Triola also stress the importance of developing antibiotics that can be used both in a hospital setting and at home, reflecting a dramatic change in the industry in recent years. “The business model essentially has moved into the outpatient setting,” Triola explains. “So while antibiotics will largely be initiated in a hospital setting, how do we set up transitions of care? How do we create pathways to ensure that our patients who have the most urgent needs receive the right antibiotics, wherever they might need them?”

Apart from everything that small pharma is doing to get drugs to patients, there are a number of initiatives to support their efforts. One such effort is CARB-X (Combating Antibiotic-Resistant Bacteria), a Boston University–based public-private partnership launched in 2016 by the US Department of Health and Human Services. The initiative is investing $500 million over the next few years in the research and development of products to tackle drug-resistant bacteria, including the work of Kimble’s and Triola’s companies.

The pendulum is starting to swing. Awareness is spreading that these superbugs are changing more rapidly than we are, and that the existing model is broken, Kimble says. It’s going to take some combination of private and public funds, working together with industry, “to make sure that the bugs don’t win.”

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