麻豆传媒

CHICAGO -- Almost a third of patients with adenoviral conjunctivitis had clinical resolution within 6 days when treated with dexamethasone/povidone-iodine ophthalmic suspension (SHP640) and almost 80% had viral eradication, according to a randomized trial reported here.

Virus eradication occurred as early as 3 days among patients treated with povidone-iodine, with or without dexamethasone. Treatment-emergent adverse events occurred more often with SHP640 compared with a vehicle solution administered to a control group, Abhijit Narvekar, MBBS, DPM, of Shire Pharmaceuticals in Lexington Massachusetts, reported at the (AAOpt) meeting here.

"No medications are currently approved in the U.S. for adenoviral conjunctivitis, and infected patients can easily transmit the disease to others," Narvekar said at an AAOpt press briefing.

"Results of this phase II study showed that SHP640 had significantly better outcomes, in terms of clinical resolution and adenoviral eradication, than with vehicle. They support its continued investigation for the treatment of acute adenoviral conjunctivitis and the continued evaluation of the results on duration of illness."

SHP640 is being evaluated for the treatment of both adenoviral and bacterial conjunctivitis in adults and children. The primary active ingredient is povidone-iodine, a broad-spectrum antiseptic, combined with the steroid dexamethasone.

"If approved, SHP640 could be a single treatment option for both adenoviral and bacterial conjunctivitis, which are challenging to differentiate clinically," Narvekar said.

Phase III clinical trials of SHP640 have begun, including studies of patients with adenoviral and bacterial conjunctivitis.

A highly contagious infection of the ocular surface, acute conjunctivitis (often called "pink eye") produces symptoms that include redness, discharge, and pain, which can lead to significant patient discomfort and lost productivity. Adenovirus accounts for most cases of acute conjunctivitis in adults, whereas bacterial conjunctivitis predominates in children.

To evaluate the safety and efficacy of SHP640, investigators conducted a randomized, double-blind, multicenter phase II trial in Asian adults with adenovirus-positive acute conjunctivitis. Study participants were randomized to SHP640, povidone-iodine without dexamethasone, or to vehicle.

Data analysis included 176 patients who had a mean age of 34.5, and men accounted for 66% of the study population. Patients received a single drop of randomized study treatment in each eye four times daily for 5 days. The primary efficacy endpoints were clinical resolution (defined as absence of watery conjunctival discharge and bulbar conjunctival redness) and adenoviral eradication (negative by cell culture immunofluorescence assay), both assessed at 3, 6, and 12 days.

Safety outcomes included slit lamp biomicroscopy (including nondilated fundus exam), best clinical visual acuity, and adverse events.

The results showed that patients treated with SHP640 had a significantly higher rate of clinical resolution on day 6 as compared with the control group (31.3% versus 10.9%, P<0.05) and a numerically higher clearance rate than the patients who received povidine-iodine without dexamethasone (18%). Both components of the composite endpoint were significantly higher with SHP640, Narvekar.

The SHP640 group also had a significantly higher rate of virus eradication day 6 compared with the control group (79.2% versus 56.5%, P<0.05). The eradication rate was numerically higher as compared with the group that received povidine-iodine without the steroid (62%).

By day 12, 95.8% of patients in the SHP640 group attained virus-free status as compared with 76.1% of the vehicle control group (P=0.0056) and 84% of the patients assigned to povidine-iodine without dexamethasone. Narvekar pointed out that SHP640 and povidine-iodine without dexamethasone led to eradication rates of 35.4% and 32%, respectively, as compared with 8.7% of the vehicle group.

No serious adverse events were reported. Treatment-emergent adverse events (TEAEs) occurred in 69% of the SHP640 group, 62.7% of patients who received povidine-iodine without dexamethasone, and 53.4% of patients assigned to vehicle. Most TEAEs were mild, and none was considered related to study treatment, said Narvekar. The common TEAEs were corneal infiltrates, punctate keratitis, and eyelid edema, all of which occurred more frequently in the comparator arms.

If results with SHP640 are borne out in the phase III trial, the therapy could represent a new standard of care for acute conjunctivitis, said press briefing moderator Edward Chu, OD, of the Long Beach VA Medical Center in California.

"Currently, conjunctivitis is essentially treated like the common cold," Chu said. "You can use lubricants, but that's not exactly treating the underlying condition. This study, along with some smaller studies and anecdotal reports, suggests that this treatment can speed the resolution of conjunctivitis."

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