Health
Bad Blood
Meningococcemia can kill its victims with stunning speed. But a new medicine tested by a Dallas doctor offers hope—if the FDA will approve it.
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Those frustrations date back to the early nineties, when Giroir began noticing an inordinate number of children showing up in the hospital’s intensive-care unit with the infection. With his earnest blue eyes and stoic jaw, Giroir seems perfect for the role of crusading young pediatrician. “You do not forget watching a child die from this disease,” he says. “I never wanted to have to look another parent in the eye and tell them that the child who only the day before was healthy and playing was now dead from a disease they had never heard of.”
Giroir began casting about for a better therapy for the infection. In 1993, while attending a conference on medical shock in Santa Fe, New Mexico, he learned that a small California biotech company called Xoma was developing products based on a recombinant form of protein, known as BPI, that increases the permeability of bacteria to bactericides. Giroir knew that BPI, which occurs naturally in the body’s white blood cells (the blood cells that help fight disease), was not only extremely effective in killing certain infections (including those caused by meningococcal bacteria) in their early stages but also effective in neutralizing the lethal toxins shed by the bacteria. “Antibiotics had always killed the bacterium itself effectively,” says Giroir. “But they could do nothing about the toxins, which were prompting the fatal symptoms. The idea was to give the immune system some extra BPI to fight off this especially strong infection.”
Since Xoma was already studying BPI medication for use in adult infections of various kinds, Giroir was hopeful that the company would jump at the chance to develop a product for meningococcemia in children. But Xoma’s management was divided on the question of testing a new product on children. “It can be that way with pediatrics,” Giroir says. “Clinical trials with new biological agents are practically unheard of with children. But I thought the nature of this disease demanded it.”
Over the next two years, Giroir cajoled, pleaded with, and nagged Xoma about BPI treatment for meningococcemia. But ultimately, it took the drama of Brianna’s death to make the company’s executives realize the urgency of the situation. “That tragedy really seemed to galvanize things,” Giroir recalls.
He finally persuaded the Food and Drug Administration’s equally cautious Center for Biologics Evaluation and Research (CBER), which regulates the testing of medications derived from biological material, to allow the testing to proceed. In the spring of 1995 Giroir and Xoma got the green light to begin testing a new BPI product, called Neuprex, for effectiveness in treating meningococcemia.
Results were positive, immediate, and dramatic. Of the 26 patients, all children, who were treated with Neuprex at Children’s and five other medical centers, only one died—a remarkable outcome, considering that the expected mortality rate had been 30 percent. “BPI seemed to give us more stability by neutralizing the endotoxins in the first forty-eight hours, which is the period during which either you or the disease is going to take charge,” says Giroir. “There’s a fine line between life and death with this disease. You are just looking for a one percent edge while you try to keep the fire under control.”
Of the initial dozen or so cases that Giroir handled during that early phase of the study, one in particular illustrates how the medication literally could mean the difference between life and death. Brad Persky, an eighteen-year-old student at Ambassador University in the small East Texas town of Big Sandy, was flown by CareFlite to Children’s four days before Christmas 1995 after his roommate found him, unresponsive and covered with a purple rash, in their dormitory room around 11 p.m.
When the young man arrived at the hospital early the next morning, according to Giroir’s notes on the case, he “was moribund. Purpura were diffuse . . . and were rapidly expanding. He had biochemical evidence of multi-organ system failure.” Brad Persky was dying.
But after receiving continuous doses of Neuprex, he slowly but surely began to bounce back. His peripheral circulation restored itself, erasing initial worries that he might lose both feet to amputation. A brief episode of hypertension—and a subsequent CAT scan that revealed evidence of a stroke suffered during the early throes of the infection—caused considerable concern. But as Persky continued to fight his way out of the infection, it appeared that BPI’s clot-busting capability may have helped him avoid long-term damage from the stroke.
In fact, so marked and rapid was Persky’s improvement that doctors soon began to wean him off the ventilator. “When they took him off it,” recalls his father, Bob Persky, a minister in the evangelical Worldwide Church of God, “I had to help him learn how to breathe again. But he just started talking a streak. Really talking. One of the nurses said, ‘Miracles really do happen here,’ and I said, ‘Praise God.’”
Brad Persky, who was moved from the ICU to a regular hospital room a week after his emergency admission, represented as good an example of BPI’s efficacy as Giroir could hope to find. Here was a patient who had arrived at the hospital knocking on death’s door. As a result of the infection, he had had a stroke and suffered from severe peripheral ischemia. Yet after treatment with BPI, the only evidence of his bout with the deadly infection was the loss of the second toe and part of the heel on his left foot to amputation.
“Here was a case where, without the BPI, I don’t think he would have lived,” says Giroir. “The BPI not only headed off the worst of the damage from the infection, but I think it helped him survive that stroke intact as well.”
Given that kind of dramatic success, one might think that BPI would have long since been okayed by CBER, especially considering that it has no known side effects. But even after three more years of testing on a total of 350 children, approval is not a sure thing.
“Our initial findings were good,” says Giroir. “But CBER must see not only a dramatic reduction in mortality, they must see it prove out over the course of enough cases that there’s no doubt that the reduction was due to use of the new medication. That’s fairly easy to do with a new medication for something that’s widespread—say, hypertension. After several thousand cases treated with a new medication, everyone can be satisfied that it is working a certain percent of the time.” Because meningococcemia is relatively rare, Giroir says, a critical mass of test subjects sufficient to satisfy CBER may never be available.
“I just hope that CBER can see that this is an exceptional situation,” he says, “a rare disease where mortality is so high that any new treatment that has shown it can reduce mortality by even a modest percentage is better than having half these kids die from this.”
For now, Giroir can only wait and hope. The last phase of the BPI study will end sometime this spring; he expects to hear from the FDA later this year. And if the agency does demand more study, he’ll continue his mission—because, he says, “What happened to Brianna was simply unacceptable.”
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