AMD drug issues linked to one practice

February 22, 2012

Since its November commercial launch, use of aflibercept (Eylea, Regeneron Pharmaceuticals) has elicited reports of post-injection sterile intraocular inflammation at a rate of 0.05% per injection, the company informed the FDA in a Feb. 13 letter. Most of the cases, however, appear to be tied to one group practice.

Tarrytown, NY-Since its November commercial launch, use of aflibercept (Eylea, Regeneron Pharmaceuticals) has elicited reports of post-injection sterile intraocular inflammation at a rate of 0.05% per injection, the company informed the FDA in a Feb. 13 letter. Most of the cases, however, appear to be tied to one group practice.

The 0.05% incidence rate is within the range reported in the literature with the intravitreal injection of other anti-vascular endothelial growth factor (anti-VEGF) agents and other drugs. The rate, however, appears to be “driven primarily by a cluster of events occurring at a single practice,” according to a report to the Securities and Exchange Commission filed Feb. 13 by Joseph J. LaRosa, Regeneron senior vice president, general counsel, and secretary. The overall rate when that medical practice is excluded from calculations is about 0.01% per injection.

William G. Roberts, MD, Regeneron vice president for regulatory development and medical safety, said in the letter to the FDA that about 30,000 doses of the neovascular age-related macular degeneration drug have been administered in the United States since November. In that time, 14 cases of post-injection sterile intraocular inflammation have been reported, as well as one case of culture-positive endophthalmitis, one case of corneal decompensation/toxic endotheliitis, and one case of corneal decompensation with no evidence of inflammation in a patient with a history of Fuchs’ corneal dystrophy.

One group practice of six physicians has administered about 700 of the doses and reported 11 cases of sterile intraocular inflammation, with one of the doctors accounting for 9 of the 11 cases, according to Dr. Roberts. The practice received multiple shipments of different lots of the drug, and the inflammation could not be traced to a single lot or a single delivery of commercial vials.

“Vials from the same lots have been widely used throughout the country. Review of drug manufacturing quality records did not reveal any product quality issues,” Dr. Roberts wrote. “We continue to work with this practice to try to define any potential cause for this cluster of cases.”

After receiving the reports of inflammation, Regeneron contacted other large practices that collectively have administered 3,500 doses of the drug, Dr. Roberts said. “These inquiries identified one potential additional case of sterile inflammation for which we have requested, but not received information,” he added.

The company has follow-up information on 9 of the 14 reported cases of inflammation; those cases either have resolved or improved, Dr. Roberts said.

“The lack of association of these adverse events with a single lot of drug product further leads us to conclude that factors other than the drug are likely to be responsible for the occurrence of these events,” he said.

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