West Coast Editor
Apparently bad - and somewhat puzzling - early news from the Phase III trial with its personalized kidney cancer vaccine sent Antigenics Inc.’s stock reeling. The company has suspended part two of the study while analyzing top-line data from the first part, and planning more changes at the firm to reduce the burn rate.
Antigenics’ stock (NASDAQ:AGEN) closed Friday at $2.97, down $2.14, or 41.9 percent.
Garo Armen, chairman and CEO of New York-based Antigenics, told investors during a conference call that the company will "work with our advisers, clinicians and the FDA on the best path forward" and will disclose full data in the next month or so.
Meanwhile, results show Oncophage (vitespen), tested in an international trial that enrolled 728 kidney cancer patients at high risk for recurrence after surgery, failed to hit statistical significance in either the primary endpoint, recurrence-free survival, or the secondary endpoint, overall survival.
The analysis found a trend in favor of the drug for recurrence-free survival, but a trend against its efficacy in overall survival. The analysis itself was triggered by "events" (recurrence of disease or deaths of patients before the cancer came back), although an independent panel’s subsequent review found that fewer events - not enough of them to conduct the analysis of the recurrence-free endpoint - actually had occurred.
Sonny Uberoi, Antigenics’ vice president of corporate communications, said the company isn’t sure how the sick patients got in.
"We’re trying to tease that out now," he told BioWorld Today. "In the next six weeks, we’re focused on doing an in-depth analysis."
Patients were randomized in a 1:1 ratio into two arms: nephrectomy plus Oncophage vaccination (the treatment arm) or nephrectomy alone (observation arm). Although the study protocol required eligible patients be free of disease at baseline, the panel review found that of the 728 patients enrolled, 124 had disease at baseline, and of the 218 events reported by investigators, 92 occurred in patients who had metastatic or residual disease at baseline.
These patients should have been deemed ineligible for the trial but had to be included in the intent-to-treat analysis once they were allowed to enroll.
"Certainly with the [clinical-events panel], you have a very comprehensive assessment, and possibly the screening techniques differ" from those used to sort the patients at the front end, Uberoi said.
Did Oncophage fail because of poor patient screening or because the drug doesn’t work?
"That’s the million-dollar question," said Ren Benjamin, senior biotechnology analyst with Rodman & Renshaw in New York. "These are pretty big trials, being run by lots of docs. Some may be a little on the messy side [when they screen patients] for whatever reason."
Benjamin said he had seen trials become skewed by such errors before, although "maybe not to this degree."
Armen, for his part, said he could "only speculate" about what happened.
"Among the reasons could be methodology of data collection, and we are addressing that issue actively now," he said. The favorable trend toward recurrence-free survival, in any case, is promising since the FDA has said that endpoint is "cleaner" than survival alone, "particularly because once disease recurs, patients are free to go and seek other treatment. So you can never rely on survival data that come out of a trial like this as the ultimate indicator of product activity or inactivity, in the full sense of the word," Armen said.
Peter Thornton, chief financial officer, repeated the company’s earlier projections that, after ending 2005 with just less than $62 million, it had enough cash to last through the first quarter of 2007.
"Clearly, we’re going through a process of reviewing our future expenditures with the objective of extending the runway of cash," Thornton said, and Armen promised news shortly on further restructuring, which will involve temporarily stopping all late-stage clinical programs and concentrating on Phase I and preclinical work.
In December, Antigenics made known a plan to reduce staff from 251 to about 170, causing about $2 million in severance costs by the end of 2005 but reducing the annual burn rate of about $75 million to about $40 million by the second quarter of this year. (See BioWorld Today, Dec. 8, 2005.)
Antigenics’ Oncophage has orphan and fast-track status from the FDA in both indications, and in November the Brain Tumor Research Center at the University of California at San Francisco started a Phase I/II trial with the drug in patients with recurrent glioma.
In October, preliminary findings from a melanoma study not intended for registration showed median survival was improved by more than 61 percent in the Oncophage-treated arm of all patients characterized as having Stage IV M1a status, compared to those who received a physician's choice of treatment regimen. Survival was extended to 20.9 months as opposed to 12.8 months. (See BioWorld Today, Oct. 12, 2005.)
Final analysis of the melanoma data is under way, Armen said Friday, and is expected to become public in "the reasonably near future."
Meanwhile, kidney-cancer patients still getting vaccine will continue on the drug while Antigenics decides the fate of the trial’s second part.
Benjamin repeated in a research note Friday his belief that if it’s feasible after a full analysis of the results a new Phase III trial with Oncophage will be conducted, which could take about three years, with the nearest launch of Oncophage in 2010. Benjamin has a "market perform" rating on the stock.