Some biostatisticians may scoff, but Antigenics is not giving up on its treatment to stimulate the immune system to fight cancer. The Lexington, MA-based biotech company (NASDAQ: AGEN) has found that nine years after its most important clinical trial began, its experimental drug appears to be helping certain kidney cancer patients live longer.
The data are still preliminary, but Antigenics has found that kidney cancer patients with an intermediate risk of relapse after they had tumors surgically removed had a 46 percent lower risk of dying if they also got the company’s vitespen (Oncophage) treatment, compared with those who didn’t. The finding comes from analyzing records of 362 patients out of 604 who enrolled in an Antigenics clinical trial from 2000 to 2005, according to research being presented today at the American Society of Clinical Oncology.
This finding, while provocative, is sure to spark debate about whether it is legit. The original study wasn’t designed to show a survival advantage for Oncophage, and the trial actually failed on its main goal—to reduce the risk of cancer relapse after tumors were surgically removed. But Antigenics has persisted over the past three years, because after further digging through the data, it found that the drug could keep patients in remission longer—as long as they were among the 60 percent of patients who have an intermediate risk of recurrence. That data was strong enough for the company to win approval to market the product in Russia, and Antigenics has applied for approval on that basis in the European Union. The company’s hope is that since the survival analysis will buttress its argument that Oncophage’s effect is real, the drug deserves a shot in the marketplace.
A strict reading of biostatistics says this whole exercise, at worst, is a “fishing expedition,” because it looks backward in time, and at best, it might be interesting fodder for generating a new hypothesis for a clinical trial. But Antigenics says it’s not practical to spend the many years and millions of dollars it would take to test this hypothesis in a new trial—especially when you’re talking about the gold standard measurement for cancer drugs—survival time.
“You can not cheat on survival,” says Garo Armen, Antigenics’ CEO. “The person is either alive or dead. It’s black or white.”
If Antigenics can ever get this drug approved by the FDA, it has potential to reach a large group of patients. About 54,000 new cases of kidney cancer were diagnosed in the U.S. last year, and 13,000 died from the disease.
At least one prominent statistician, Richard Simon of the National Cancer Institute, has looked at the data and told the company he considers it a valid exercise, Armen says. The principal investigator of the trial, Christopher Wood of M.D. Anderson Cancer Center in Houston, TX, said in a company statement, “these interim results show that Oncophage has a real promise of improving survival in patients with earlier-stage disease for whom current prognosis remains poor.”
Still, Armen stopped short of saying this finding is definitive on whether Oncophage helps patients live longer. The company still needs to track down more patients, and keep following them for at least another nine months for the data to become mature, he says. The absolute numbers are also small—just 18 patients on the Oncophage group of the study had died as of early January (about 10 percent), compared with 32 who died in the control group (18 percent) at the same cut-off date, Antigenics said.
The company is being urged by about two dozen thought leaders to package this data together and send it to the FDA, although Antigenics hasn’t decided whether to do that yet, because it’s possible the FDA may not even consider taking a look at it, Armen says. For now, he’s hopeful this will strengthen Antigenics’ hand with European regulators.
Part of what intrigues researchers so much, and keeps the Antigenics dream alive, is the way the drug is designed to work, by boosting the immune system to fight cancer like a virus. Realization of this immunotherapy concept has eluded science for decades, although Seattle-based Dendreon just reported a significant advance for the field last month when it showed in a clinical trial of 512 men that its immunotherapy helped men on the treatment live longer with minimal side effects.
The Antigenics treatment is different than Dendreon’s—which uses a standard genetically engineered protein on cancer cells to spark the immune system to fight. The Antigenics method doesn’t rely on one biomarker on cancer cells, but rather hopes to spark the immune system to fight multiple biomarkers.
It does this by slicing out a portion of a patient’s tumor, freezing it, and shipping to the Antigenics plant in Lexington. There, it is chopped up, and key proteins filtered out. The treatment is shipped back to the doctor, then injected back into the patient to “teach” the immune system to spot the hallmarks of cancer cells and mount a defense against them. Patients usually get their personalized vaccine four to six weeks after tumors are removed, the company has said.
Dendreon’s success created a short-lived burst of enthusiasm for other cancer immunotherapy companies, including Antigenics, but it’s clear the company needs a bigger break than that. Its stock closed Friday at 73 cents, and it had just $14.5 million in cash and investments left in the bank at the end of March. Antigenics is hopeful that the survival benefit is too enticing for regulators to ignore, and that something can be worked out to keep the product alive.
“We can’t accomplish this without regulatory innovation,” Armen says. All the company asks, he says, is that regulators “hear us out on the science, the biology, the facts.”