Public Citizen has filed a petition urging the FDA to rescind its approval of the Seprafilm bioresorbable membrane, which is used to prevent postoperative adhesions, citing adverse patient events, including at least 21 deaths.
The consumer advocacy organization maintains that Seprafilm, which was developed by Genzyme, has not been shown to be safe and effective. In addition to the reported deaths, the FDA’s MAUDE database includes 524 adverse events — such as bowel obstruction, abscess, peritonitis, fever, fluid collection and inflammatory reaction — linked to Seprafilm, the group says.
The FDA approved the device in 1996 on the condition that Genzyme, which was acquired by Sanofi in 2011, would conduct a postmarket safety study. The agency had concerns about the number of serious adverse events in the Seprafilm arm of one of two pivotal efficacy studies, according to the petition. These events included abscesses and pulmonary emboli.
Public Citizen alleges both the pre- and postmarket studies “were plagued by a host of serious issues,” including protocol violations and problematic reanalysis of data. According to the petition, agency inspectors sent a warning letter to a principal investigator who failed to maintain blinding throughout the study. In addition, the investigator failed to report some adverse event data and lacked informed consent documentation.
The group also maintains that the postmarket study, dubbed Study 601 and conducted to assess the device in reducing the incidence of bowel obstruction following abdominopelvic surgery, failed to meet its primary endpoint. Further, patients in the Seprafilm group were significantly more likely to experience anastomotic leak, peritonitis, vomiting and fistula versus those in the control group.
“Rather than accept these results — which were potentially disastrous with respect to the continued marketability of Seprafilm — Genzyme, in coordination with the Study 601 Steering Committee, engaged in several extensive post hoc re-analyses of the data designed to re-characterize the failed trial as a success,” the petition maintains. For example, Genzyme allegedly created a new definition for bowel anastomosis, a term that had been interpreted different ways by investigators. The U.S. National Library for Medicine defines anastomosis as a surgical connection between two structures.
As a result of the redefinition, the steering committee reclassified an unknown number of subjects as having a bowel anastomosis.
The petition also points to dangers related to off-label use of the device, including with Cesarean sections and pediatric surgery, the petition states. It notes that in December 2013, Genzyme agreed to pay $22.28 million to settle false claims allegations related to Seprafilm. Whistleblowers came forward accusing Genzyme sales representatives of improperly showing doctors and other staff how to create Seprafilm “slurry.”
To make this slurry, Seprafilm sheets were cut into small pieces, dissolved in saline and ultimately used in laparoscopic surgery — an unapproved use. Genzyme was accused of knowingly causing healthcare organizations to submit false and fraudulent claims for reimbursement.
In an e-mailed statement to IDDM, Sanofi and Genzyme say they are committed to the safe and effective use of Seprafilm. “We stand behind the clinical trial results and nearly 15 years of postmarketing surveillance data reported to the FDA for Seprafilm. We continue to advise physicians to follow the approved product labeling, including directions for general use.”