GAITHERSBURG, Maryland — A US Food and Drug Administration (FDA) advisory committee yesterday generally endorsed the novel ophthalmic product ReSure Sealant, but votes were split because most panel members wanted a narrower indication than the manufacturer was seeking.
The product is a synthetic polyethylene glycol hydrogel that forms a temporary barrier designed to prevent leakage of clear corneal incisions after cataract or intraocular lens surgery. Although the technology is similar to other available products, none are licensed for ocular use in the United States.
Manufacturer Ocular Therapeutix, Inc, had been seeking the indication "for intraoperative management of clear corneal incisions with a wound leak demonstrated by a Seidel test, and for prevention of postoperative fluid egress following cataract or intraocular lens placement surgery."
The 11 members of the FDA's Ophthalmic Devices panel of the Medical Devices Advisory Committee voted 9 yes, 1 no, and 1 abstain to endorse the product's safety; 5 yes, 3 no, 3 abstain for efficacy; and 5 yes, 1 no, 5 abstain with regard to the sealant's benefits outweighing its risks.
Several panel members who voted "no" or "abstain" said they would have voted "yes" if the clause about prevention were removed, because they did not think the manufacturer's data supported prophylactic use. Many also advised the FDA to include qualifiers in the labeling, including the fact that the sealant is only temporary, that it should not be used for copious leaks or lacerations, and that it should not be marketed as a substitute for sutures, despite the manufacturer's data demonstrating the sealant's superiority over sutures.
The panel also uniformly endorsed the need for a postmarketing study to further assess the product's efficacy, as well as safety endpoints such as increased intraocular pressure and endophthalmitis.
Panel Chair Eve J. Higginbotham, MD, told Medscape Medical News, "It's very promising. It's the first device of its kind. The FDA is considering the recommendations of the committee."
Superior to Sutures
Speakers presented data from Ocular Therapeutix's pivotal trial, a prospective, randomized, parallel-group, controlled, multicenter, subject-masked study involving a total of 488 adult patients undergoing uncomplicated clear corneal cataract surgery by 41 surgeons at 24 US sites.
The patients were randomly assigned (305 sealant, 183 suture) after intraocular lens implantation and assessment for leaks, using both the Seidel test and a special Calibrated Force Gauge developed by the company for the study. Stromal hydration was allowed in both the sealant and suture study groups.
A bit surprisingly, about 50% of the patients had experienced spontaneous leaks before randomization and study treatment, according to Terry Kim, MD, professor of ophthalmology at Duke University, Durham, North Carolina, who presented study data on behalf of the company.
The primary endpoint, the proportion of eyes with any clear corneal incision/suture leakage, as determined by positive Seidel test indicating fluid egress within the first 7 days after surgery, was met by just 4.1% of the patients who received sealant compared with 34.1% of those who received sutures. The difference was highly significant, with P < .0001 for both noninferiority and superiority.
Effectiveness was not influenced by patient sex, age, site, use of stromal hydration, or number of sealant applications, Dr. Kim said.
The sealant, which is meant to cover the clear corneal incision and protect the epithelium in the first few postoperative days, had sloughed off by day 3 in two thirds of the patients and had disappeared in all by day 14. In contrast, 87.4% of the sutures were still in place at day 28.
Overall and device-related adverse events were significantly less frequent with the sealant. Adverse events related to the sutures occurred in 30.6% of patients compared with 1.6% of those in the sealant group (P < .0001).
The most common of these adverse events were subconjunctival hemorrhage (0.3% with sealant vs 21.9% sutures; P < .0001), intraocular pressure 30 or above or 10 mm Hg over baseline (5.3% vs 8.2%; P = .2499), and worsening best-corrected visual acuity of more than 2 lines (6.9% vs 4.9%; P = .4400).
Both foreign body sensation and eye irritation were infrequent in both groups, but they were significantly more common in the patients who received sutures. Major and serious adverse events were rare, not device-related, and did not differ significantly between sealant and suture groups, John Hovanesian, MD, from the University of California, Los Angeles, Jules Stein Institute, reported on behalf of the company.
After lengthy discussion on a variety of device-related topics that FDA officials asked them to address, including issues related to the design of the postmarketing study, panel members voted separately on the sealant's safety (question 1), efficacy (question 2), and whether they believe the benefits outweigh the risks (question 3).
Brad H. Feldman, MD, from Philadelphia Eye Associates in Pennsylvania, voted yes to questions 1 and 2. However, he said, "I abstained on the last question because theoretically the benefits of closing the wound outweigh the risk of the device, but the real benefits are yet to be known."
Alice Y. Matoba, MD, an ophthalmic surgeon at Baylor College of Medicine in Houston, Texas, said earlier in the meeting that she routinely sutures her cataract patients and expressed skepticism that the sealant actually is superior to suturing. Nonetheless, she voted "yes" to all 3 questions.
"If I were voting purely based on a scientific viewpoint, I would have abstained on questions 2 and 3, but I think the vast majority of cataract surgeons do not suture their wound.... If there's a small leak, they hydrate and then they're done. So, if they use [the sealant] in addition to hydration, there will be a benefit," Dr. Matoba said.
Neil M. Bressler, MD, from the Wilmer Eye Institute at Johns Hopkins Hospital in Baltimore, Maryland, abstained on all 3 questions "because the proposed indication includes prevention of postoperative fluid egress. I did not see any evidence that it does indeed prevent it effectively, and therefore I can't balance the benefits and risks. Had the indication been limited to the first half, I do think it was shown to be safe and effective, and I think the benefits outweigh the risks."
Jayne S. Weiss, MD, from the Louisiana State University Health Science Center in New Orleans, who had earlier expressed concern regarding the transience of the sealant's effect and the fact that it should not be used for copious leaks, said she voted yes for 1 and 3, but no for 2. "I would like to see this approved, with changes and wordsmithing in the proposed indication for use.... I voted no on question 2, but easily if a few words were put in there, my vote would have been yes."
FDA advisory committee members are vetted for conflicts of interest and waivers are granted for participation if necessary. No waivers were granted for this meeting.
FDA Medical Devices Advisory Committee, Ophthalmic Devices Panel. September 19, 2013.
Medscape Medical News © 2013 WebMD, LLC
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Cite this: FDA Panel Endorses ReSure Sealant, With Provisos - Medscape - Sep 20, 2013.