EyeWorld Asia-Pacific September 2014 Issue

September 2014 29 EWAP GLAUCOMA Reason for the meeting The MIGS workshop was co- sponsored by the FDA and AGS. “My division worked with AGS members to develop the agenda as well as the discussion topics,” Dr. Eydelman said. “CDRH is committed to facilitating innovation in the ophthalmic arena, and the clinical trial topics discussed at this workshop will aid in this goal.” The meeting was held to explore how FDA approval of MIGS devices can be further clarified and streamlined, Dr. Kahook said. The FDA does not currently have firm guidance documents to help with pivotal trials for these devices. “Each company must ‘recreate the wheel’ when they meet with the FDA,” Dr. Kahook said. “The FDA is burdened by the added work that comes with so many new MIGS devices seeking regulatory approval.” He said that a unified guidance that addresses many of the vague aspects of pivotal trials in the MIGS space could help the FDA. “One of the key purposes of this important meeting was to facilitate good communication between the FDA team and physicians who are participating in these new minimally invasive glaucoma surgery device trials,” Dr. Vold said. “By meeting together, both physicians and the FDA can hopefully better understand how to successfully conduct these pivotal MIGS trials, and ultimately better serve glaucoma patients across the country.” What was discussed Dr. Eydelman’s discussion focused on the increase in MIGS devices being developed. She also highlighted the importance of better descriptions of clinical trial components to evaluate the safety and effectiveness of MIGS devices. Dr. Kahook discussed efficacy endpoints for MIGS device trials. He clarified when “efficacy” and “safety” can be combined to achieve composite metrics and how efficacy with MIGS devices should not be held to the same standards as more invasive devices that treat glaucoma. “I recommended (and the participants appeared to agree) that we should also look at what percentage of patients in the MIGS treatment group (with any device) achieved significant IOP lowering (20% lower) compared to the control group independent of what the final overall mean IOP was for the entire treatment cohort,” he said, indicating that participants believed it would be significant if 20% to 50% of patients in the MIGS group achieved an additional 20% IOP lowering beyond that achieved from the control group. Dr. Vold’s presentation focused on suprachoroidal outflow as a surgical target for the treatment of glaucoma. He discussed how the current paths for aqueous outflow and suprachoroidal outflow should be a therapeutic target. Suprachoroidal outflow would offer a robust pressure gradient, a continuous and absorptive reservoir, and a pharmacologic precedent, he said. The presentation also discussed the way that supraciliary stenting could create a conduit to the suprachoroidal space. Dr. Vold said suprachoroidal outflow could be a promising MIGS target because preliminary safety results seem to be similar to other MIGS devices; the anatomical approach could help create a more elegant procedure; and it has potential for the best IOP-lowering efficacy. Important issues One of the important issues with MIGS devices is to clarify what the “significance” bar is for IOP lowering using these devices that are safer than traditional devices but might have lower efficacy compared to more invasive approaches, Dr. Kahook said. “An important concept is that it might be very significant if only a small percent of the MIGS group achieves IOP lowering beyond that achieved by the control because the downside is insignificant.” One of the topics that came up at the meeting was the specifics of the MIGS device studies and the definitions pertaining to glaucoma.“We should have some reproducibility among the studies,” Dr. Vold said, citing the first Glaukos trial for the iStent, which was a 1-year trial with no washouts, and explaining that there is not necessarily uniformity in studies for MIGS devices. Dr. Eydelman said the design of the trial is important for future approval of these devices. “One must clearly determine the subjects that should be enrolled and what endpoints would demonstrate device safety and effectiveness,” she said. “There was quite a debate about how advanced the glaucoma should be to be a part of these trials,” Dr. Vold said. “The one thing that was very clear to me is that the people who had the most experience in the clinical trials had a different perspective than those who were less experienced.” These studies can be difficult to enroll, Dr. Vold said, and this is an aspect that needs to be addressed. He added that enrolling patients earlier in the spectrum of glaucomatous disease could potentially be advantageous for patients. Dr. Eydelman said that the CDRH is planning to develop guidance that will detail what patients should be enrolled in these trials. Approval for other MIGS de- vices Dr. Kahook said that over the next 6 months to 3 years there will likely be other MIGS devices approved for use in the U.S. “There are MIGS devices that are closer to being marketed in the U.S. that do not require the PMA route for approval,” he said. Dr. Kahook said that he believes the next devices going through the PMA route will likely make it to market in the next 3 years. EWAP Editors’ note: Dr. Vold has financial interests with AqueSys, Glaukos, Ivantis, Transcend Medical, and NeoMedix. Dr. Kahook has financial interests with Aerie Pharmaceuticals (Bedminster, NJ, U.S.), Alcon (Fort Worth, Texas, U.S.), ClarVista Medical (Aliso Viejo, Calif., U.S.), Allergan (Irvine, Calif., U.S.), Glaukos, Oasis Medical (Glendora, Calif., U.S.), New World Medical (Rancho Cucamonga, Calif., U.S.), Mile High Ophthalmics, OcuTherix (Stillwater, Minn., U.S.), ShapeTech (Colorado Spring, Colo., U.S.), and Shape Ophthalmics (Denver, Colo., U.S.). Contact information Eydelman: malvina.eydelman@fda.hhs.gov Kahook: malik.kahook@ucdenver.edu Vold: svold@cox.net