Licking wounds from the clinic

Disappointing pivotal data from Gensia Inc., ProCyte Corp. and Telios Pharmaceuticals Inc. illustrate the difficulties of replicating earlier successful studies.

The importance of robust Phase II studies is again illustrated by GNSA, which last week reported that its 2,700-patient Phase III study of Protara to prevent heart attack and adverse events in patients undergoing coronary artery bypass graft (CABG) surgery failed to show statistical significance (see BioCentury Extra, Oct. 17)

"Looking back, I think everybody here would say we would have done a larger Phase II," said David Hale, chairman, president and CEO of the San Diego company. GNSA did one Phase II study with multiple doses in about 120 patients.

Hale said it's not yet clear why the new trial didn't duplicate the positive results seen in the high-dose group in its U.S. Phase III study using a rigorous definition of heart attack, and in sub-groups in its Phase III European and Canadian study.

"To the extent possible, we tried to make everything the same," he said. "But you have changes in techniques by the surgical community, and whether they were associated with the outcome of the study we don't know."

One such change is in the kind of cardioplegia used - the use of chemical compounds or cold during cardiac surgery to cool the heart down in order to prevent reperfusion injury following surgery.

Standard of care