What’s new in ocular allergy?

The ocular allergy treatment market will experience expansion over the next several months. New ocular allergy drugs have been approved.

Issue: April 15, 2000

Approximately 20% of the U.S. population suffer from allergy, with an estimated 50% of those allergy sufferers requiring ocular medication for relief of symptoms. During the past year, three new medications have been approved for marketing: Alamast (pemirolast potassium ophthalmic solution 0.1%) from Santen Inc. (Napa, CA); Alocril (nedocromil sodium ophthalmic solution, 2%) from Allergan Inc. (Irvine, CA); and Zaditor (ketotifen fumarate ophthalmic solution, 0.025%) from CIBA Vision (Duluth, GA).

As the ocular allergy market continues to expand, it may become more difficult for ophthalmologists to choose a treatment for their patients. As these most recently approved therapeutic interventions for ocular allergy penetrate the U.S. market, ophthalmologists will have 10 ocular allergy medications to choose from. Therapy choices will be based on efficacy, safety and convenience of dosing, in addition to comfort of administration for the patient. The aim of treatment includes decreased irritation, minimum dosing, ease of compliance and few or no side effects.

Alamast

Alamast ophthalmic solution received Food and Drug Administration (FDA) approval for the temporary prevention of itching of the eye due to allergic conjunctivitis. Symptomatic response to therapy may be evident within a few days, but frequently requires longer treatment.

“Alamast is the only mast cell stabilizer that has been approved for the prevention of the itch associated with allergies and allergic conjunctivitis,” Gregg J. Berdy, MD, a cornea/external disease specialist, told Ocular Surgery News. “Mast cell stabilizers work very well. When these drugs work to stabilize the mast cell, there is no degranulation of the mast cell and, therefore, the allergic cascade of mediators is eliminated.” Mast cell stabilizers work by preventing the allergic system from turning on, he said.

In vitro and in vivo studies have confirmed that Alamast hinders the antigen-induced release of inflammatory mediators from human mast cells. In addition, Alamast may prevent the chemotaxis of eosinophils into ocular tissue and blocks the release of mediators from human eosinophils.

In a study by Graves, Amdahl and Abelson, presented at the 12th Congress of the European Society of Ophthalmology in Stockholm, Sweden, Alamast-treated patients reported significantly more days without ocular itching when compared with placebo-treated patients. The study was conducted during the ragweed allergy season. Patients began dosing prophylactically with Alamast or placebo, four times per day, starting about 1 to 2 weeks before the historical onset of the ragweed allergy season.

Statistically significant differences were observed as early as the first week of allergy season. A post-season conjunctival allergen challenge (CAC) model confirmed that the mean itching at 3 minutes after challenge and worst itching during the first 10 minutes after challenge were both significantly lower in Alamast-treated patients than in placebo-treated patients. The study additionally confirmed that Alamast is safe with respect to adverse events, visual acuity and intraocular pressure (IOP). There were no notable differences between treatment groups in biomicroscopy or ophthalmoscopy. The drops were well tolerated when administered four times per day up to 4 months.

Alamast’s indication is for the prevention of itching of the eye due to allergic conjunctivitis. Additionally, decreased itching may be obvious within a few days after treatment is initiated, but longer treatment may be needed in some patients who required up to 4 weeks. In clinical studies lasting up to 17 weeks with Alamast, adverse reactions included headache, rhinitis and cold/flu symptoms at an incidence of 10% to 25%, which were consistent with the underlying course of the disorder. The occurrences of these events were generally mild and were similar to those found in the placebo group.

Alocril

“The new trend today for allergy is dual action or multiple action drugs,” Stefan D. Trocme, MD, cornea/external disease specialist, told Ocular Surgery News. “Alocril stabilizes and prevents actions from eosinophils and neutrophils and it prevents neuronal actions.” Alocril additionally prevents other surface cells from secreting inflammatory mediators and decreases chemotaxis. According to Dr. Trocme, Alocril is the first ocular allergy drug to have more than three multiple actions.

Alocril is to be used twice per day — once in the morning and once at night. It has a rapid onset of action. “You don’t have to wait for days [for Alocril to work] like you do with traditional mast cell stabilizers,” Dr. Trocme said. “Alocril will act within minutes of application.” While some ocular allergy medication are infamous for their stinging upon instillation in the eye, this is not true with Alocril, he said. There is little stinging associated with Alocril use, making it a comfortable therapy for ocular allergy sufferers.

Alocril was approved by the FDA for the treatment of itch associated with allergic conjunctivitis. The drug’s safety profile allows it to be used in children 3 years and older. Recommended dosing is one or two drops in each eye twice per day until the pollen season is over or exposure to the offending allergen is terminated. The most frequently reported adverse event was headache, which occurred in about 40% of patients studied, about the same as in patients receiving placebo.

Zaditor

“Zaditor is unique because of its mechanism of action,” Michael Raizman, MD, cornea/external disease specialist from the New England Eye Center and Ophthalmic Consultants of Boston, told Ocular Surgery News. “It is a powerful antihistamine and also stabilizes mast cells and inhibits eosinophils.”

In clinical trials, Zaditor was found to inhibit the release of chemical mediators like histamine and leukotrienes from sensitized mast cells and to inhibit the binding of histamine to the H₁ receptor. This drug additionally decreases eosinophil chemotaxis and activation. Zaditor is indicated for the temporary prevention of itching of the eye due to allergic conjunctivitis.

As a selective, noncompetitive histamine receptor antagonist, Zaditor inhibits the activity of a major chemical mediator involved in type 1 hypersensitivity reactions. As a mast cell stabilizer, Zaditor calms the major cellular component of the allergic cascade, preventing the mast cell from releasing the various chemical mediators that are responsible for both the immediate hypersensitivity and the late phase allergic reactions.

In clinical trials, Zaditor proved statistically and clinically significant efficacy in the prevention of itching at grading intervals ranging from 15 minutes to 12 hours after dosing. The beginning of the preventive effect of Zaditor is rapid and occurs within minutes of treatment. The duration of this effect is 8 to 12 hours.

In three CAC studies, Zaditor showed to be significantly more effective than vehicle in preventing the development of ocular itching. The drug had a rapid onset of action that occurs within minutes of the drug being instilled. Additionally, Zaditor has been proven effective when administered up to 12 hours prior to allergen exposure. This drug is safe and well tolerated in adults and in children ages 3 and 11 years.

In controlled clinical trials, the incidence of adverse events (ocular and non-ocular) were similar in vehicle in placebo and ketotifen-treated groups.

For Your Information:

Gregg J. Berdy, MD, can be reached at 456 N. New Ballas Road, Ste. 386, Creve Coeur, MO 63141; (314) 993-5000; fax: (314) 993-5558. Dr. Berdy has no direct financial interest in any of the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Michael Raizman, MD, can be reached at 750 Washington St., Boston, MA 02111; (617) 636-7625; fax: (617) 636-4866. Dr. Raizman has no direct financial interest in any of the products mentioned in this article. He is a clinical investigator or a paid consultant to Santen, CIBA and Allergan.

Stefan D. Trocme, MD, can be reached at Department of Ophthalmology UTMB, Clinical Sciences Bldg., Room 340, Galveston, TX 77550-0787; (409) 772-8104; fax: (409) 772-8106. Dr. Trocme has received research grants from Allergan.

Allergan Inc. can be reached at 2525 Dupont Drive, P.O. Box 19534, Irvine, CA 92713-9534; (714) 246-4242; fax (714) 246-5499.

CIBA Vision can be reached at 11460 Johns Creek Parkway, Duluth, GA 30097; (800) 533-1676; fax: (678) 415-3592.

Santen Inc. can be reached at 555 Gateway Drive, Napa, CA 94558; (707) 254-1750; fax: (707) 254-1769.

Reference:

Kjellman NIM, Stevens MT. Clinical experience with Tilavist: an overview of efficacy and safety. Allergy. 1995;50(suppl 21):14-22.