By Jim Schutze
By Rachel Watts
By Lauren Drewes Daniels
By Anna Merlan
By Lee Escobedo
Harley will have no finger for a wedding ring, but that's not important, Brock says.
"I just thank God every day that he let us keep her," Brock says.
But Berkeley, California-based XOMA agreed to take on the trial and collaborate with New York University in the development of Neuprex. XOMA banked on the possibility that Neuprex could have applications in other treatments for shock after it was approved to treat meningococcal sepsis.
After Tashica, the next seven patients who were given the treatment in subsequent months also responded well and they lived. Giroir expanded the study.
"The bottom line is that we started to have a study where we only wanted six to eight patients, but because everybody was living, we, with the approval of the FDA...extended the trial to 25 to 26 patients," he says.
The results were astonishing. Tashica was the cover girl for XOMA's 1995 annual report. "Tashica is Number One," the cover said beside a smiling and radiant Tashica. The treatment would be designated an orphan drug and put on the FDA's fast track for a second, much expanded and much more expensive trial. It seemed almost miraculous.
In 1996, XOMA started what was called "Phase III" of Neuprex trials. Jack Castello, chairman, president and chief executive officer, says his company is ultimately a business, a publicly traded company, that needs to make money, but that doesn't mean it isn't interested in finding effective treatments for rare diseases. In the case of the Neuprex trials for meningococcal sepsis, it just made good emotional and economic sense, he says.
"We were approached by people like Brett Giroir who knew of the characteristics of the drug who said two things: One, there is a real need," he says. "There are children, even babies, dying horrible deaths of this disease every day, every year. When we get into it, it's probably one of the most horrible ways to die of any that you could ever dream of, and certainly for a child it's got to be just devastating, the amputations, the limbs turning gangrenous, the horrible eruptions, 20 different fluid lines into a baby. There's a lot of emotional reason to do it."
From a drug-development standpoint, he says, both the massive endotoxin production and the relative predictability of the disease helped make meningococcal sepsis an excellent testing ground to help determine the ability of Neuprex to treat sepsis that resulted from other causes, such as a blood infection from a gunshot wound. It was a bit of a tough sell, but Castello eventually prevailed and received approval to proceed.
The second trial employed what is known as "double-blinded, placebo-controlled" methods. That meant that neither doctors nor patients knew who got the drug. Doctors such as Giroir were so convinced that Neuprex helped that they did not want to even use a placebo on any children, but the government requires it.
In the case of Neuprex, XOMA set out to prove the drug reduced deaths. Once the study started, however, it became clear that proving a mortality reduction would be a problem. The rapid progression of the disease made it terribly difficult to transport study subjects to participating hospitals before they died.
During the first Neuprex study, which Giroir set up himself, hospitals all over Texas were notified, and transportation by Careflight was arranged. Giroir could get the patients to his door or to the door of a hospital such as Texas Children's Hospital in Houston quickly. That wasn't the case this time around. The entire United States and Canada and the United Kingdom were included, and both transportation and education were problematic. Patients were dying before they could be included in the study.
"All the cases of meningococcal sepsis don't occur in convenient places. They occur in Oshkosh, and they occur in Greenville, South Carolina. They don't always occur in Dallas, Texas, and San Francisco and New York City where all the big hospitals are," says Patrick Scannon, chief scientific and medical officer for XOMA, who keeps a photograph of a child stricken with meningococcal sepsis over his desk as a reminder of his mission.
Not only did it take time for doctors to identify the condition and get patients to a hospital participating in a study, but most patients often had already wasted many valuable hours at home dealing with what seemed like the flu.
"The average time to getting into the study was six hours from the time of first antibiotics to the time they got the study drug," Giroir says. "The issue was that two-thirds of the patients that were going to die, died by that six-hour time period."
Scannon says despite the lack of proof that Neuprex was having a significant impact on the number of deaths, their trial was showing Neuprex had a benefit to what is known as "morbidities," or other ill effects of the disease.