Sepsis: Blood Poisoning Kills Thousands, But No Drugs to Help

July 18, 2012— -- Rory Staunton's death started with a simple cut on his arm.

Rory, a 12-year-old New Yorker, cut himself when he dove for a basketball at his school gym in late March, according to the New York Times. Two days later, he was vomiting, feverish and had a pain in his leg. A few days later, on April 1, Rory died at NYU-Langone Medical Center of a kind of blood poisoning known as sepsis.

His death, and others, point to a major problem in treating sepsis -- there are currently no drugs approved to fight it. The only drug developed for it, called Xigris, was withdrawn from the market in 2011, when the drug failed rigorous testing required to maintain regulatory approval. The drug's fall from grace highlights just how difficult fighting sepsis is, and leaves doctors wondering whether developing a drug will ever be possible.

Bleak Prognosis, Then Brief Promise

About 750,000 people in the U.S. each year get sepsis, and about 225,000 of them die from it. The condition is an infection of the bloodstream, and it can arise from any number of infectious bugs that attack the body, such as meningitis, pneumonia and infections of the skin or bladder, to name a few. The blood poisoning is caused not by the germs themselves, but by the body's hyper-response to those germs, when it releases a barrage of chemicals that can lead to organ failure.

Those chemicals cause the body to go into shock, and patients have symptoms such as chills, fever, confusion, rapid heartbeat, headache and skin rashes.

The best shot patients have is for doctors to treat them early, ideally giving a patient antibiotics and fluids within the first hour that they show symptoms. Dr. Andre Kalil, an associate professor of medicine at the University of Nebraska Medical Center, said even in the best-case scenario, antibiotics don't always help.

"Unfortunately even with the best antibiotics and supportive care, a third of these patients will die," Kalil said. "We don't have other drugs that actually can act in the body in response to the infection. We just don't."

That wasn't always in the case. In 2001 when the U.S. Food and Drug Administration approved Xigris, made by the pharmaceutical company Eli Lilly, hopes were high that it would keep thousands of patients from dying. The company's initial clinical trials of the drug showed that it reduced the chances of dying by 20 percent in patients at risk of developing sepsis.

But the drug's initial performance was somewhat disappointing. Some patients benefited from the drug, others did not, and doctors had trouble defining which type of patient would benefit the most. The drug was also very expensive, so many hospitals put protocols in place that strictly limited when the drug could be given -- usually when all other methods had failed.

Dr. Jonathan Janes, medical director of acute care for Eli Lilly, said the company was encouraged by studies of the drug in real-life clinical settings, which showed that it kept many patients alive.

"We felt encouraged by those results, they seemed to support that the drug worked," Janes said. "Obviously, you need your clinical trial data, but these results were nice to have."

But questions about the drug's effectiveness and safety began to surface. Patients getting Xigris had a slightly increased risk of bleeding. Increasingly skeptical that the expensive drug was actually effective, European regulators asked Eli Lilly to conduct a second clinical trial. The results were the nail in Xigris' coffin -- the trial showed that the drug was little better than placebo. Based on those results, Eli Lilly voluntarily pulled the drug from the market in October 2011.

"This was the first drug specifically licensed for sepsis, which leaves us essentially with nothing now," said Dr. Greg Martin, director of the medical and coronary intensive care units at Emory University.