FDA approves bepotastine for ocular itching

Key Points

St. Louis-The FDA has approved bepotastine besilate ophthalmic solution 1.5% (Bepreve, ISTA Pharmaceuticals) as a twice-daily prescription eye drop treatment for ocular itching associated with allergic conjunctivitis in patients aged 2 or more years.

The approval was based in part on single- and multicenter clinical studies using the conjunctival allergen challenge (CAC) clinical model of allergic conjunctivitis. These studies showed both statistical and clinical significance of the drug compared with placebo, said Gregg J. Berdy, MD, FACS, assistant professor of clinical ophthalmology, Washington University in St. Louis.

Although he is not an investigator in the FDA studies of bepotastine, Dr. Berdy presented as an outside clinician on behalf of ISTA to the FDA Advisory Panel.

Bepotastine joins several other medications available by prescription or over-the-counter for the treatment of ocular itching associated with allergic conjunctivitis, and the addition is welcomed, he said, explaining that most patients will use multiple medications over time for various reasons.

"Having another choice is always a good thing. Not all drugs work for all patients, and that's why we need more choices," Dr. Berdy said.

He added that seasonal allergic conjunctivitis affects about 20% to 30% of the general population, which translates to approximately 60 million to 90 million individuals in the United States, and many of them are miserable when allergens trigger a flare-up of their symptoms. The availability of another proven topical agent increases the likelihood that a patient will experience relief, even if more than one product has to be tried before the most clinically effective and comfortable agent is found.

Well evaluated

Bepotastine also performed well in evaluations of ocular comfort, Dr. Berdy said. In a study in a pediatric population, no clinically or statistically significant difference was found in the ocular comfort of bepotastine or placebo either immediately upon instillation or 5 minutes afterward.

"Bepotastine is a comfortable agent as well as an effective one that could be used in a broad base of patients," he said, noting its approval for use in children as well as adults and its efficacy in reducing tearing and total nonocular symptoms.

Bepotastine is a non-sedating, highly selective antagonist of the histamine H1 receptor, with negligible affinity for histamine H2 or H3 receptors. It has a stabilizing effect on mast cells and has been shown in guinea pig experiments to suppress the migration of eosinophils into inflamed conjunctival tissues. Other experiments have shown bepotastine to inhibit the activity of various cytokines and leukotrienes such as IL-5, TNF-alpha, and leukotriene B4 (LTB4) that are active in eliciting an allergic response.

Clinical trials

During the testing required for FDA approval, the effectiveness and safety of the investigational drug in reducing ocular itching were studied in a single-center, double-masked, randomized, placebo-controlled, 7-week clinical trial using the CAC model.

Eligible subjects were randomly assigned to receive either bepotastine (n = 35) or placebo (n = 36). They were tested approximately 14 days after confirmatory CAC was performed, and then again approximately 28 days and 42 days after the confirmatory test. At the first of these visits, the CAC was performed 16 hours after instillation of a single drop of bepotastine or placebo; the challenge was performed 8 hours after instillation in the subsequent visit and 15 minutes afterward in the third visit. An ocular itching grading scale of 0 to 4 with increments of 0.5 was used to evaluate the subjects' response.

Bepotastine was statistically superior to placebo at all study visit observation time points for reducing CAC-induced ocular itching. The drug achieved ≥ 1 unit clinical improvement in ocular itching on the scale of 0 to 4 at all time points in both pivotal trials following the CAC tests given 15 minutes and 8 hours after ophthalmic dosing (p ≤ 0.0001). A statistically significant benefit was seen for bepotastine compared with placebo (p ≤ 0.005) 16 hours after ophthalmic dosing at all time points in both trials, but there was not ≥ 1 unit clinical improvement at a majority of time points in itching, as required for clinical significance.

In another CAC study, bepotastine was shown to reduce tearing at 8 hours following instillation. The study was a multicenter, double-masked, randomized, placebo-controlled, 7-week clinical trial; 43 subjects each were randomly assigned to receive the active drug or placebo. Ocular tearing was graded as absent or present.

Bepotastine was statistically superior to placebo (p = 0.016) in reducing tearing in the CAC model of allergic conjunctivitis for at least 8 hours after ophthalmic dosing.

According to Vicente Anido Jr., PhD, president and chief executive officer of ISTA, bepotastine is a safe and effective way to treat the itching caused by ocular allergies because of its multiple mechanisms of action and rapid onset of action. He also said that plans for the launch of the product are proceeding rapidly.