AAO/SOE 2008: Ganciclovir Gel Allows Fewer Relapses in Patients With Herpetic Keratitis

Emma P Hitt, PhD

November 10, 2008

November 10, 2008 (Atlanta, Georgia) — Pooled data from 3 phase 2 trials and 1 phase 3 trial in patients with herpetic keratitis suggest that 0.15% ganciclovir ophthalmic gel is better tolerated and has a lower relapse rate than 3% acyclovir ophthalmic ointment.

Herbert E. Kaufman, MD, a former professor of ophthalmology, pharmacology, and microbiology at Louisiana State University Medical School, in New Orleans, presented the findings in a poster session here at the 2008 Joint Meeting of the American Academy of Ophthalmology and the European Society of Ophthalmology.

Acyclovir and ganciclovir are both potent nucleoside analogs that function as virustatic agents, suppressing the replication of herpes simplex virus. According to the researchers, intracellular ganciclovir triphosphate concentrations are approximately 10 times higher than those of acyclovir, and decline more slowly, with a half-life of more than 24 hours.

Dr. Kaufman and colleagues assessed data from 4 randomized clinical studies conducted in over 200 patients in Europe, Asia, and Africa, comparing the efficacy and tolerability of 0.15% ganciclovir ophthalmic gel and 3% acyclovir ophthalmic ointment. Patients had dendritic or geographic ulcers. The primary end point was healing of the ulcer.

In addition, a small case series of 18 patients with adenoviral keratoconjunctivitis was conducted to compare the ganciclovir gel with preservative-free artificial tears.

Findings in patients with herpetic keratitis were consistent across the 4 studies. Ganciclovir was associated with a lower relapse rate than acyclovir. Healing rates ranged from 83% to 89% for ganciclovir and 71% to 92% for acyclovir, which was not significantly different. However, a pooled intention-to-treat analysis of the 3 studies revealed a statistically significant difference in the primary end point of ulcer resolution between the groups (85% vs 71% for acyclovir vs ganciclovir; = .04).

Relapse rates were 0% to 4% for ganciclovir and 0% to 14% for acyclovir. Investigator-assessed efficacy determined a high degree of patient satisfaction in 66.8% of ganciclovir-treated patients, compared with 54.9% of the acyclovir-treated patients.

Overall tolerability was better with ganciclovir than with acyclovir, although some measures were similar among the groups. One study showed that the incidence of stinging/burning was much higher with acyclovir ointment than with ganciclovir gel.

The case series of 18 subjects with adenoviral keratoconjunctivitis found that ganciclovir may accelerate recovery, compared with preservative-free artificial tears.

"Several studies summarized in this poster from around the world showed that ganciclovir is more effective and better tolerated than acyclovir, Dr. Kaufman told Medscape Ophthalmology. "Because the ganciclovir preparation is a gel, it may be better tolerated than acyclovir," he added.

In a phone interview with Medscape Ophthalmology, Penny Asbell, MD, noted that, overall, patients tend to prefer a gel to an ointment: "It's definitely easier to use and tolerate, and this may result in the advantage of increased compliance with treatment," she said. Dr. Asbell is professor in the Department of Ophthalmology and director of the Cornea Service and Refractive Surgery Center at Mount Sinai School of Medicine in New York City.

According to Dr. Asbell, in the case series of patients with adenoviral keratoconjunctivitis, ganciclovir appeared to have efficacy. "This needs to be explored and, if it does turn out to be effective, it would certainly be a great opportunity," she said. "At the present time, at least in the United States, there is nothing available to treat adenovirus infections, which are a significant cause of keratoconjunctivitis and can cause a severe infection and loss of vision; effective treatments would definitely be welcome."

The studies were supported by Laboratoires Théa. Dr. Kaufman is an employee of Sirion Therapeutics, which has an exclusive licensing agreement with Laboratoires Théa of France for the American rights to develop and market ganciclovir ophthalmic gel. Dr. Asbell has disclosed no relevant financial relationships.

2008 Joint Meeting of the American Academy of Ophthalmology (AAO) and the European Society of Ophthalmology (SOE): Scientific Session PA015. Presented November 9, 2008.

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