Updated August 4, 2014 at 11:30 a.m. with comments from panel members.
The FDA’s General & Plastic Surgery Devices Advisory Panel today narrowly recommended approval for Cohera Medical’s polyurethane-based TissuGlu adhesive for the approximation of tissue layers to bind subcutaneous dead space between the tissue planes in large flap surgical procedures, including abdominoplasty.
The panel voted unanimously that TissuGlu is safe; 6-5 that it is effective; and 6-4 with 1 abstention that the adhesive’s benefits outweigh its risks.
"I think that it’s effective, but it wasn’t clear," Ohio State University’s Dr. Michael Miller said. "It wasn’t a nice story in the way the data were presented, but the whole story put together, I think, it has effect."
Large flap surgical procedures such as abdominoplasty, a cosmetic abdominal surgery that removes excess skin and fat, are associated with complications including hematoma, seroma, necrosis and wound healing problems. Seroma formation is the most commonly reported complication, and the current standard of care for preventing seromas in abdominoplasties is the placement of surgical drains to allow excess fluid to exit the body, according to FDA background materials released ahead of the meeting. according to FDA background materials released ahead of the meeting.
"I voted yes, I felt it was effective," Mayo Clinic’s Karla Ballman said. "I was swayed by the fact that almost ¾ of the patients did not require any invasive procedure and I do feel that placement of drains is invasive. It’s not so much the pulling out, but living with the drains over the 7-day period is an invasive procedure and it eliminates that. However, I was a bit torn because I don’t know that the data presented reflects the broad indication as it was written by the company. I think it needs to be more limited."
If the FDA follows its panel’s recommendation and approves TissuGlu, informed consent of patients will be key, Dr. Ann Leitch of University of Texas Southwestern Medical School/Center pointed out, because data from the clinical trials showed that patients closed with the adhesive vs. drains who develop seromas post-operatively will require needle aspirations of their seromas.
"I think this is one of these situations where informed consent is critical because patients have different opinions about whether they’d rather be stuck with a needle or have the drain," Dr. Leitch noted. "There’s not data that [TissuGlu is] unsafe."
TissuGlu has been approved in Europe since September of 2011 for the same indication as this U.S. Premarket Approval application. Cohera conducted 4 clinical investigations of TissuGlu including 2 pivotal studies at 5 centers in the U.S. and 2 feasibility studies in Europe.
The first randomized, controlled, single-blind clinical study in 150 subjects across 5 U.S. centers compared standard wound closure techniques including drains during abdominoplasty to standard wound closure techniques, drains, plus TissuGlu. Follow-up visits were performed daily until drain removal, and then at post-operative days 14, 30, 60, and 90, and at 6 months and 1 year, the FDA noted.
To prove effectiveness, subjects on whom TissuGlu was used had to have 30% reduction in time to drain removal compared with the control group, with a criterion for drain removal of less than 30 mL of fluid per drain in a 24-hour period.
Based on these criteria, TissuGlu in conjunction with drains was not effective in reducing the days to drain removal or reducing the cumulative wound drainage output, the federal watchdog agency noted, but Cohera claims that time to drain removal is not an informative endpoint with respect to adherence of large flap tissue planes.
The second randomized, controlled U.S. trial of 130 abdominoplasty patients across 5 investigational sites compared those closed with standard surgical closure techniques and just TissuGlu to patients closed with standard surgical closure techniques and just drains.
TissueGlu met its primary effectiveness endpoint in this trial for both the per protocol and intent-to-treat populations, which was based on the number of post-operative invasive treatments, including removal of an in-dwelling drain, needle aspiration to remove fluid from a clinically-diagnosed palpable seroma, invasive action to the drain or drain wound such as repositioning or re-attaching the drain retention sutures, and re-insertion of a drain.
In addition, Cohera claims that abdominoplasty clinical data and case report data from commercial use of TissuGlu in other large flap procedures supports the use of TissuGlu in multiple anatomical areas including mastectomy without immediate reconstruction, transverse rectus myocutaneous flap reconstruction, latissimus dorsi flap reconstruction, and inguinal lymph node dissection.
Northwestern University’s Dr. Murad Alam was among 5 of 11 panelists who voted that TissuGlu is not effective. "I really wanted to like this product because it’s the first in vivo strong glue and I can see the anecdotal data suggesting it works and plastic surgeons feel like it works, the patients feel like it works; but based on the best data that was available to us, I didn’t feel like [data from the clinical trials proved it works]," he said.
Early this year Cohera closed on a $26 million Series D round, saying it plans to use the proceeds to advance TissuGlu through the PMA process and to secure CE Mark approval in the European Union for Sylys, another surgical sealant designed for intestinal anastomosis procedures.