Three recent reports of pericardial effusion prompted Corautus Genetics Inc. and partner Boston Scientific Corp. to voluntarily suspend treatment in a Phase IIb study of a catheter-delivered VEGF-2 biologic for treating severe angina.
Following the suspension, Atlanta-based Corautus also terminated its previously announced public offering of 7.5 million shares, which would have pulled in gross proceeds of $26.5 million.
"These were extremely difficult decisions," Richard Otto, president and CEO of Corautus, said during a conference call, adding that the company hopes to resolve the issues "as quickly as we possibly can."
Corautus’ shares (NASDAQ:VEGF), which had fallen by more than $1 around mid-morning Tuesday, rebounded by the end of the day to close at $3.40, down 62 cents, or 15.4 percent.
Initiated in August 2004, the Phase IIb GENASIS (Genetic Angiogenic Stimulation Investigational Study) is designed to evaluate Corautus’ vascular endothelial growth factor-2 (VEGF-2) candidate administered using Boston Scientific’s Stiletto endocardial direct injection catheter system in patients suffering severe Class III or Class IV angina who are not suitable for traditional revascularization procedures. The trial’s primary endpoint is the increase in exercise tolerance time on a treadmill. Secondary endpoints include decrease in angina as determined by improvement in angina class, decrease in nitroglycerin use and increase in blood supply to the heart.
To date, 295 of the total 404 patients have been treated with the drug-device combo, and up to this point, the study had been progressing as scheduled. Two months ago, the trial’s data safety monitoring committee issued a positive recommendation following its third and final safety review.
However, a "recent cluster of serious adverse events" of pericardial effusion in the trial caused Natick, Mass.-based Boston Scientific to recommend temporarily halting treatment, Otto said.
Pericardial effusion is caused by excess fluid filling the pericardial sac surrounding the heart. A total of seven cases have been reported in the trial. While a small risk for pericardial effusion was not wholly unexpected given the catheter-based administration, concern came after the three most recent cases occurred within a 10-day period, Otto said.
"It gave us cause to pause here and take a look at what may be causing this," he said, adding the companies would be working to gather data and determining whether any link exists that could explain the recent spate of adverse events.
Four of the seven occurrences - including all three of the most recent cases - required secondary intervention to reduce the fluid in the pericardial sac before it could impair blood flow. Overall, out of 295 patients, the percentage of those needing further intervention due to pericardial effusion has been about 1.4 percent.
At this time, "we have no indication at all" that the adverse events are related to Corautus’ VEGF-2 therapeutic, Otto said. He further clarified that data from the trial still remains blinded, and it’s unknown whether the instances of pericardial effusion occurred in the treatment or placebo groups. Patients in the placebo group received an injection of saline rather than VEGF-2.
"Until we can really get our hands around the data," the companies won’t be able to give specific guidance on the product’s development timeline, he said.
Corautus and Boston Scientific previously had expected to release data from the Phase IIb angina trial late this year or early next year, with a Phase III study to start in the first half of 2007.
"Our goal still is to continue to recruit through the 404 [patients], and then meet with the FDA to proceed with a Phase III trial," Otto said.
The clinical halt affects only the angina trial. Studies of Corautus’ VEGF-2 product in diabetic neuropathy and critical limb ischemia are ongoing.
The company did, however, agree to withdraw its public offering of 7.5 million shares, which priced Friday at $3.85 per share.
The stock was expected to be issued today, and the company had anticipated using the $26.5 million in proceeds for working capital and other general corporate purposes, including clinical trials and manufacturing costs. (See BioWorld Today, March 13, 2006.)
At the end of 2005, Corautus had nearly $31 million in cash and investments, and it lost $4.6 million in the third quarter. The cash on hand is expected to sustain operations through the first quarter of 2007.
"We are still feeling very comfortable with that statement," said Bob Atwood, chief financial officer, who projected a monthly cash burn of $1 million to $1.5 million.
"There is some likelihood that there will be some variation to that burn rate," he said.
The company will continue evaluating financing alternatives, Atwood said, but "we think this [trial suspension] is only temporary, so we’re not factoring in any major change."