Rx Perspectives

Bepreve: Winner by a Nose

By René Luthe, Senior Associate Editor

US physicians and allergy sufferers got another option for the treatment of ocular itching associated with allergic conjunctivitis when bepotastine besilate ophthalmic solution 1.5% (Bepreve, Ista Pharmaceuticals) was approved by the FDA in September. Perhaps just as importantly, researchers say, they got a medication that also addresses the nasal symptoms that often accompany allergic conjunctivitis.

Selective and Effective

What makes Bepreve effective, according to one of its clinical investigators, is that it is a highly selective H-1 antagonist. While Tom Macejko, MD, of Eyecare Associates of Greater Cincinnati concedes that the phrase "highly selective" is thrown out a lot at pharmaceutical presentations, he emphasizes that in this case, it means that this drug will make a difference to patients who find side effects of antihistamines problematic.

"Bepreve hits the most important histamine site while affecting the other sites to a much lesser degree," he claims.

Results from two seven-week phase 3 conjunctival allergen challenge studies of Bepreve showed it to be "as effective in suppressing ocular itching in patients with more severe itching as in patients with all grades of ocular itching," according to the company.

One hundred and fifty-seven patients were enrolled in the masked, randomized, placebo-controlled clinical studies. Of that number, 113 exhibited bilateral ocular itching grades of at least 3 at study visit two. Subjects were assessed at 15 minutes, eight hours or 16 hours after instillation of the drops at study visits spaced two weeks apart during the enrollment period.

Ista reports that the difference in mean itching grades (placebo-active) for the more severely affected subjects was within plus or minus 0.1 unit of the differences for the entire intent-to-treat population.

Treating Nasal Symptoms

As for the nasal symptoms that bother so many ocular allergy sufferers, Terry Kim, MD, associate professor of ophthalmology, cornea and refractive surgery at Duke University Eye Center, points out that secondary endpoints for those phase 3 trials show a significant reduction in total nonocular composite symptoms (TNSS) including rhinorrhea. The total TNSS score was a 77% reduction from baseline within seven minutes after the dose. And at eight hours after instillation, researchers found an 84% reduction in TNSS.

"This is really exciting because I would say that about 75-90% of these patients have both ocular and nasal symptoms," says Dr. Kim. He adds that Bepreve is not only an antihistamine, but also a mast cell stabilizer.

The drug also demonstrated efficacy in the trials on other allergy symptoms such as excessive tearing. Ninety percent of patients had no excessive tearing with one drop of Bepreve vs. placebo. There was a 76% reduction in eyelid swelling from baseline within three minutes vs. placebo.

Safe for Pediatric Patients

Another advantage, Dr. Macejko noted, is that Bepreve is approved for patients as young as two years. "Some of the over-the-counter medicines you shouldn't use in children, because of possible cardiovascular effect," he says.

A poster presented at this year's Association for Research in Vision & Ophthalmology annual meeting presented subpopulation data from the six-week, placebo-controlled, parallel-group safety study. The number of patients in the 10 to 17 years of age group who reported an adverse event after instilling Bepreve was very similar to the number who instilled placebo (22% vs. 20%).

Dr. Macejko points out that the drug's record of safety, for even pediatric patients and during its previous nine years on the market in Japan, make it particularly well-suited to allergy patients.

"I find people who have allergies, regardless of what drop you give them, are going to use it when their eyes are bothering them," he says. "If they feel the need to use the drop more frequently, they are going to use it more frequently."

Bepreve is indicated for twicedaily use. It is packaged in a 10 ml bottle, providing 60 days of therapy for one co-pay, the company says, making it an economical choice for patients. OM