Copyright Dickinson FDA Webview at www.fdaweb.com. Republished by permission.

2/24/2015

Avedro Inc. CEO David Muller was verbally battered by several injured LASIK patients during public presentations 2/24 at a joint meeting of two FDA advisory committees as he led his company’s efforts to win an approval recommendation for a new drug/device combination to treat eye disorders progressive kerataconus and ectasia. Muller, the presenters charged, headed Summit Technology in the 1990s when it won a corrupt approval for the first LASIK-indicated excimer laser that permanently damaged their eyesight and “ruined” their lives.

Now he’s seeking approval for an “orphan”-designated NDA for riboflavin ophthalmic solutions with UVA irradiation by Avedro’s KXL System for use in corneal collagen cross linking for the treatment of the conditions underlying progressive keratoconus and corneal ectasia following refractive surgery. Despite its unapproved status in the U.S., the combination is already being promoted on Avedro’s Web site as an integrated enhancement of LASIK surgery outcomes, restoration of corneal strength, halting progression of keratoconus and ectasia, and slowing or eliminating the development of acute keratoconus.

Before they voted 10-4 with one abstention to recommend approval for the keratoconus indication and 6-4 with four abstentions for the ectasia following refractive surgery (LASIK) indication, the Dermatologic and Ophthalmic Drugs Advisory Committee and Ophthalmic Devices Panel of the Medical Devices Advisory Committee heard 14 public commenters give four-minute presentations. The first four urged approval, citing worldwide successful use of the new technology outside the U.S., and the suffering of an estimated 2 million keratoconus American victims who are without access to the therapy.

There were 1,268 corneal transplants performed in the U.S. in 2013, the Cornea Society’s David Glasser told the panel. “I couldn’t be happier if your votes today mean I will have performed my last corneal transplant,” he said.

But the remaining 10 public presenters, while frequently conceding the case for keratoconus victims in Avedro’s new technology, delivered a relentless stream of condemnations of the refractive surgery medical-industrial-FDA collaboration that they complained had ruined their lives, led to depression and suicide through an “epidemic” of dry eye, blurred vision, starbursts, haloes, night-driving difficulties and other vision problems.

The panel also heard a presentation, delivered in his absence, by former CDRH ophthalmic devices branch chief Morris Waxler, who led the team that approved the first Summit Technology LASIK device and has since recanted. Delivering for him, injured LASIK activist Paula Cofer slammed Muller’s role as Summit Technology CEO in introducing the first LASIK lasers through a corrupt FDA evaluation process. She alleged that he was responsible for “thousands, perhaps tens of thousands of LASIK patients who developed ectasia as a result of their trust” in the process. LASIK surgeons, she said, don’t report the ectasia cases they cause, and are complicit in an industry-wide cover-up. If FDA approves Avedro’s combination product, she predicted it will lead to off-label use of Avedro’s next enhancement, LasikExtra, already being promoted on its Web site and in the marketplace.

Then it came Matt Kotsovolos’ turn [speaking for Dean Kantis] to lambaste Muller for “ruining” his vision through “huge” (reportedly $1 million) contributions to the late Sen. Edward Kennedy’s 1994 re-election campaign “in exchange for political FDA access” that led to the Summit device’s approval in October 1995. Kotsovolos also read from what he said was a transcript of a presentation to a professional group by the Cleveland Clinic Foundation’s Cole Eye Institute eye surgeon Ronald R. Krueger, in which he admitted that LASIK-caused ectasia occurred much more frequently than the procedure’s FDA-accepted 1% total adverse event rate.

Muller, who has long bragged about the closeness of his FDA relationships, took to the podium several times during the panel discussions, but he did not respond to his critics. In one appearance he explained that deficiencies in the clinical data supporting the KXL System application, pointed out by many panel members, resulted from data prepared by an unnamed “small German company” that developed the technology and ran out of money before it could complete the studies and Avedro acquired them as-is.

Among the Avedro data deficiencies mentioned by panelists were the NDA’s lack of patient satisfaction surveys, which CDRH ophthalmic devices director Malvina Eydelman told the meeting FDA was “committed to,” and the complete lack of any data from studies done with the KXL device itself ─ instead the panelists were forced to accept Avedro’s contentions that this device was to all important extents, identical to a different device, the UVX which was used in all the studies.

Despite these and other deficiencies, the panel voted with barely muted misgivings for the primary indication, progressive keratoconus, and much more reluctantly for the second ─ and reputedly far more profitable ─ ectasia after LASIK indication.