West Coast Editor

An esophageal cancer patient's death from pulmonary embolism in GenVec Inc.'s Phase II study with TNFerade that a physician said was "possibly" related to the drug caused the FDA to place all trials on clinical hold.

The Gaithersburg, Md.-based company's stock (NASDAQ:GNVC) fell 47 percent on the news, closing Thursday at $1.20, down $1.06.

"To the FDA, it really doesn't matter the degree of relation - possibly, probably, definitely," said Paul Kessler, executive director of clinical research, adding that the company had done an analysis of similar events with TNFerade, which uses an adenovirus to deliver the gene for tumor necrosis factor-alpha by direct injection into tumors.

"In that top-dosing cohort, in addition to the death, there were two other cases of pulmonary embolus, which in both cases were attributed by investigators as being related to underlying disease," Kessler told BioWorld Today. "Plus we had an asymptomatic detection of a small pulmonary embolism. At that point we had four, and I think it was cause for concern."

Phase II studies for locally advanced pancreatic, esophageal and rectal cancer will be halted until the FDA's concerns can be addressed, said Paul Fischer, president and CEO of GenVec.

"The FDA called us on Tuesday afternoon and said, We've looked at this and we're not sure it's related to the drug, but we want to investigate it further,'" he told BioWorld Today, adding that the company expects a letter from the agency.

Until the embolisms, Fischer said, researchers found no adverse events related to the drug during three dose escalations, nor had embolisms surfaced in the pancreatic study, which enrolled more patients at higher doses.

"It could be related to the site of administration or some other factor," he said.

Earlier this week, GenVec presented a poster on the Phase II esophageal study at the 16th EORTC-NCI-AACR conference in Geneva, and included data about the embolisms, but the FDA already had the data, Fischer said.

While awaiting more details from the agency, GenVec is putting together a package to address their concerns.

"We want to be responsive and have them look at it quickly," Fischer said, adding that "it's never good news to have drug toxicity, but that is what the trials are set up to do - and we don't even know that [the embolisms are] drug related."

GenVec also has a gene-therapy cardiovascular product, BioBypass angiogen, in Phase II trials for peripheral vascular disease. It delivers the VEGF 121 gene by adenovector to the legs so that new blood vessels are formed in the diseased ischemic tissue. GenVec licensed VEGF 121 gene from Scios Inc., of Fremont, Calif., on a worldwide basis for all gene-therapy applications.

No Comments