By Lisa Seachrist

Washington Editor

ROCKVILLE, Md. — Citing unspectacular clinical data, an FDA advisory panel voted 6-0 to recommend that the agency not approve Genzyme Inc.'s Sepracoat for the prevention of post-operative abdominal scarring.

While finding Sepracoat safe in the clinical studies of gynecological surgery, the FDA's General and Plastic Surgery Devices Panel denied the Cambridge, Mass., company's product marketing application on the grounds the company failed to establish efficacy.

The panel instead recommended that the company test not only whether the product reduced the number of adhesions but also whether Sepracoat caused a reduction in the serious side effects associated with abdominal adhesions.

"We knew this was going to be a hard sell, it is a very tough model," Henri Termeer, Chairman and CEO at Genzyme, said. "It is a question of judgment and we will have to come back to the committee with a very crisp picture next time."

Genzyme's stock (NASDAQ:GENZ) fell 10 percent to $22.312, a drop of $2.437.

Sepracoat is a 0.4 percent solution of hyaluronic acid designed to prevent scarring associated with abdominal surgery. The hyaluronic acid forms a temporary barrier that prevents fibrin from forming adhesions that can lead to pelvic pain, small bowel obstruction, and infertility.

Unlike its predecessor on the market, Genzyme's Seprafilm, which is an implantable film that separates tissues at the site of incision, Sepracoat bathes the abdominal cavity in an attempt to prevent de novo adhesions arising in areas just beyond the surgical incision.

The company tested Sepracoat in patients undergoing gynecological laparotomy mostly for problems associated with infertility. In a multicenter study, they compared 107 patients who received Sepracoat to 108 who received the control solution of phosphate buffered saline (PBS). At a "second look" operation, the surgeons participating in the trial assessed whether there were adhesions in any of 23 pre-specified sites.

The company presented data indicating that patients who received Sepracoat had 4 percent fewer adhesions than those on the placebo.

The committee, however, stated that it was underwhelmed by the reduction in adhesions and raised questions about potential bias because more of the women in the control group had pre-existing adhesions.

"In order to accept the company's argument that preventing adhesions will have clinical benefit, I would have to see a 15 to 20 percent reduction in adhesions," panel member Ricardo Azziz, professor of obstetrics and gynecology at the University of Alabama at Birmingham, said. "Otherwise, I question the clinical significance."

Richard Moscicki, chief medical officer at Genzyme, noted that during the committee meeting for Seprafilm, reduction in adhesions was enough for the panel to recommend the device, but now they seem to want more. "This was a real switch from the previous situation," Moscicki said.

"However, with Seprafilm it was a very black and white situation," Termeer noted. "We have a less clear cut benefit with Sepracoat."

Titus Duncan, a panel member and general surgeon in Atlanta, noted that women in the control group had more pre-existing adhesions, indicating they may have biological causes that predisposed them to adhesions. If that were the case, then Sepracoat would be even less effective than the company had shown. "You need to start on level ground to effectively compare the two," Duncan said.

The committee recommended that the company study surgeries where the incidence of adhesions and adverse events from those adhesions are more common than in the gynecological surgeries studied. The committee also suggested that the company study Sepracoat's ability to prevent small bowel obstruction, infertility and abdominal pain that can result from abdominal adhesion

Termeer noted Genzyme remains "very committed to this field." He said the company would look into working with European centers where both Sepracoat and Seprafilm are being marketed.

"I really believe that the biggest benefit to patients will come with the combination of Sepracoat and Seprafilm," he told BioWorld Today. *