FDA advisory panel okays icodextrin for adhesions.(Food and Drug Administration)(Innovata PLC)(Clinical report)

GAITHERSBURG, MD. -- A 4% icodextrin solution was recommended for approval by a Food and Drug Administration Advisory Committee for the reduction of postsurgical adhesions in women undergoing gynecologic laparoscopic surgery that includes adhesiolysis.

If approved by the FDA, Innovata PLC's Adept--a clear, non-viscous glucose polymer solution that stays in the intraperitoneal cavity for at least 4 days--would be the first product licensed in the United States for adhesion reduction in laparoscopic gynecologic procedures. The product has been marketed in Europe since June 2000 by Baxter International Inc. for use in both laparoscopic and nonlaparoscopic gynecologic and general surgery. A 7.5% icodextrin solution is also used in the United States and Europe for continuous peritoneal dialysis.

The "approvable with conditions" vote of the FDA's Obstetrics and Gynecology Devices Panel was unanimous, despite the fact that only one of the FDA's three prespecified primary efficacy end points was reached in the company's pivotal clinical trial. Due to a lack of specific data on women undergoing procedures in which they would not be expected to require adhesiolysis, the committee narrowed the scope of the indication the company originally sought, which would have also included the product's use for primary adhesion prevention.

"I support approval based on the fact that there is no currently available way to prevent adhesion reformation, and the safety data are reassuring," said panel member Dr. Marcelle I. Cedars, director of reproductive endocrinology at the University of California, San Francisco. Fellow panelist Dr. Jonathan W. Weeks, director of the Maternal-Fetal Medicine Center at Norton Suburban Hospital, Louisville, Ky., noted, "The safety data are convincing. I'm not as convinced about efficacy. I wouldn't have supported it if we hadn't limited it to procedures requiring adhesiolysis."

The committee's evaluation of the product's efficacy was complicated by two unforeseen issues relating to Innovata's pivotal U.S. study, in which 449 women undergoing laparoscopic peritoneal cavity surgery for gynecologic procedures requiring adhesiolysis were randomized to receive either Adept or lactated Ringer solution (LRS) as both intraoperative irrigant and postoperative instillate.

One issue was that the LRS, which was intended as a control, also turned out to be somewhat effective in reducing adhesions. The second was that the FDA's predetermined statistical threshold for defining clinical "success" may have been too stringent, the company argued--and several panel members agreed. The committee also grappled with the relative significance of the numerous secondary end points included in the company's submission.

Elizabeth Peers, Ph.D., Innovata's director of clinical development, presented the findings of the 16-center, double-blind, randomized, controlled clinical trial in adhesion reduction. Surgical indications among the 449 patients included pelvic pain, infertility, adhesions, and endometriosis; some had more than one diagnosis.