A single child in Arkansas is a patient in a clinical trial for a rare cancer -- an example, an oncologist said, of how researchers follow the science where it leads.
"All drug development is a high-risk proposition," Dr. Martin Birkhofer said. "Even big pharma companies are science-driven, and will follow the signals and the biology they see in their labs in the earliest stages of clinical trials."
Birkhofer is senior vice president and chief medical officer of medical research company Gradalis Inc. of Dallas.
The child is a patient of Dr. Kathleen Neville at Arkansas Children's Hospital. Neville is a pediatric oncologist at the hospital and director of the experimental therapeutics program at the University of Arkansas for Medical Sciences.
The cancer is Ewing's sarcoma, a pediatric cancer of the bone. About 225 children and teens are diagnosed with Ewing's sarcoma in the United States every year, Neville said.
In Arkansas, the number is likely in the single digits. The cancer is commonly treated with chemotherapy and radiation. What's most dangerous for patients is if they relapse.
"Every time you relapse, your survival rate goes down," Neville said in an interview. "We can save some kids, but for a lot of kids, it's a death sentence. Some kids survive, but with every relapse their chances are worse.
"When a kid comes to me, those statistics don't matter," Neville said. "Every child is his own entity whose chances are either zero or 100 percent. I'll fight my heart out for the 100 percent."
That determination led Neville to Gradalis. The patient was approved for the trial in 19 days, she said, as opposed to the typical three months or so. The treatment isn't a drug, she said, but a vaccine.
"We call these engineered autologous tumor cells," Birkhover said by phone from Dallas. "They come from the patient. It's a highly personalized cancer immunotherapy.
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"We obtain tumor tissue from patients at surgery. In our manufacturing facility in Carrollton, we use molecular biology techniques to insert two genes of the DNA of the tumor.
"The end result or consequence of the insertion of genes into the tumor cells is they become much more recognizable by the immune system. As tumors grow, they find clever ways to camouflage themselves from the immune system. An enormous lot has been learned about how this works and how to reverse that."
The tumor cells are irradiated, Birkhofer said, so they're still alive but can't divide. The vaccine is injected once a month into the patients. From four to 12 injections can be made from the tissue removed during surgery.
"What we have seen, using indicators of human immune response, is a fairly profound and sustained immune reaction. We believe this is specific to the tumor."
Another benefit, Birkhofer said, is the absence of "systemic adverse events. There's an irritation of the skin that's short-lived but there's no real system toxicity as you might expect with chemotherapy."
The treatment for Ewing's sarcoma came out of a trial in which 19 different tumors were treated, Birkhofer said, mostly tumors in adults.
"The loudest signals were for ovarian cancer and Ewing's."
In cooperation with Mary Crowley Cancer Research Centers of Dallas, Ewing's patients were studied for the effect of the vaccine. The results were described in the August 2016 edition of the medical journal Molecular Therapy.
Sixteen patients were given individualized treatments of the vaccine -- called Vigil by Gradalis -- and compared with 14 who were not. Long-term follow-up showed a survival benefit "without evidence of significant toxicity," the journal article said.
"Specifically we report a 1-year survival of 73% for Vigil-treated patients compared to 23% in those not treated with Vigil," the journal article said.
The median overall survival rate for Vigil patients in the study was 731 days. The median overall survival rate for the non-Vigil patients was 207 days.
Patients in the trial came from "all around," said Shannon Cagina, chief operating officer of Mary Crowley.
"One was from Germany. Georgia. Florida. Colorado. Fort Worth. Dallas. Houston. When you have a new drug for something, and there's been nothing new for 30 years, people will move heaven and earth for their kids."
The Arkansas child, she said, was traveling to Dallas for the trial. Neville wanted the trial to open in Arkansas, Cagina said, "because it's really hard for a patient to travel for a clinical trial."
Other sites in the Ewing's trial, according to the Gardalis website, are in Los Angeles, Miami, New York City, Cleveland, and Lebanon, N.H.
Children's cancers are rare, Cagina said, so new treatments may have little economic benefit for pharmaceutical companies.
"Where do you get an investor to say, 'Here's a billion dollars?' Someone has to pay for all the research. Parents think big, bad evil pharma isn't doing anything for children, but they have shareholders to answer to."
That's why nonprofit institutions such as hers are so important, Cagina said. Without philanthropy, Neville said, "there's no way we could do this."
Birkhofer said Gradalis sees commercial opportunities in treating Ewing's sarcoma, and believes the Vigil technology can work for other cancers.
Neville said several more Ewing's sarcoma patients are under her care. And several more have died since she came to Little Rock about 15 months ago.
"The bad days are really bad. Who do I have to tell I have no other options, or the disease has progressed?" Neville said. "One or the other or both are awful."
Most new treatments, especially for cancer, are developed for adults, she said, and pose a question for medical science.
"Do you do more good by extending the life of a 70-year-old for 10 years, or saving the life of a child who will grow up and thrive and is our future?"
Metro on 12/27/2016