Injection lowers IOP

Future use of drug may help stabilize patients’ medication regimens

Early primary open-angle glaucoma.
Source: Pfizer Inc.

Using an anterior juxtascleral depot (AJD) of anecortave acetate in open-angle glaucoma (OAG) patients may help reduce problems with medication compliance and persistence, said Alan L. Robin, M.D., associate professor of ophthalmology and associate professor of international health, Bloomberg School of Public Health, Johns Hopkins University, Baltimore.
Dr. Robin is leading a controlled study on the use of anecortave acetate administered as an anterior juxtascleral depot in the sub-Tenon’s space. The investigators concluded that a single injection of anecortave acetate has the potential to reduce IOP for at least three months.
Dr. Robin, his co-investigators, and Alcon (Fort Worth, Texas) released the study results at the World Glaucoma Congress in Singapore this past July.
Full clinical assessment will continue through a six-month period. This study and subsequent research may provide a basis to file a new drug application for anecortave acetate with the U.S. Food and Drug Administration in 2009, according to an Alcon press release.
Anecortave acetate via an injection every three months could avoid many of the compliance and adherence problems seen in patients, Dr. Robin said.
“One thing this offers is a way for the patient to forget about taking a drug regularly and getting the drop in the eye, because the physician does administers the drug,” he said.
An AJD every three months is within the reasonable realm of time between visits to the eye physician for glaucoma patients—usually every three to six months, Dr. Robin said.

Study details

Anecortave acetate, currently prescribed to some age-related macular degeneration (AMD) patients as the drug Retaane (anecortave acetate suspension, Alcon), is a steroid derivative, Dr. Robin said. However, anecortave acetate does not have any of the usual side effects that steroids have, and it actually obviates some of the effects of steroids.
The interim results with the use of anecortave acetate were from a three-month period. All patients had OAG without pseudoexfoliation or pigment dispersion. There were no patients with ocular hypertension. For inclusion in the study, patients had to have an IOP of 24 mm Hg to 36 mm Hg in the study eye. The mean patient age was 64.5 years old; 57% of the patients were female.
Eighty-five patients were randomly assigned to receive 3 mg, 15 mg, or 30 mg of anecortave acetate or 0.5 mL of anecortave acetate vehicle. Under topical anesthesia, the drug was placed 3 mm to 5 mm from the limbus, inferiorly and injected slowly with a 30-gauge needle.
Patients were evaluated at two weeks, six weeks, and then at three months. Beginning at week six, if the patient had an IOP of 21 mm Hg or higher for two consecutive visits within one week of each other, additional IOP-lowering medications were added.
The study required patients to maintain an IOP of less than 21 mm Hg, which led some patients to exit the study because their IOPs remained above 21 mm Hg—even though their IOP had actually lowered compared with when they began the study.
Thirty-eight percent of patients from all three injection groups were classified as a treatment success at three months, compared with 24% in the vehicle arm. Fifty percent of patients with the highest dose (30 mg) were considered a success.
The mean IOP reduction in the three active arms was 7.2 mm Hg at three months, compared with 1.4 mm Hg for the vehicle arm. “Because the study included a vehicle treatment group, strict and conservative study criteria were used to protect and ensure patient safety,” Dr. Robin and co-investigators wrote. As a result, a patient with a significant IOP reduction (e.g., 34 mm Hg to 22 mm Hg) would not be considered a success under these criteria.”
The most common side effects were eye pain, foreign-body sensation, and blurred vision, according to presented data. Sixty-four percent of the patients who experienced eye pain said that it was related to the injection procedure.
If anecortave’s duration is actually as long as these initial studies shows, possibly up to 6 to 12 months, it would be a welcome addition to the field, said Douglas J. Rhee, M.D., assistant professor of ophthalmology, Department of Ophthalmology, Glaucoma Section, Massachusetts Eye & Ear Infirmary, Boston.
“An alternative dosing strategy might greatly enhance compliance since it does not require the patient to administer it themselves on a daily basis. Anecortave would be a welcome addition to our therapeutic armamentarium if effectiveness and duration are confirmed,” Dr. Rhee said.

Editors’ note: The research conducted by Dr. Robin and co-investigators is sponsored by Alcon (Fort Worth, Texas). Dr. Robin has financial interests with Alcon, Ista (Irvine, Calif.), and Merck (Whitehouse Station, N.J.). Dr. Rhee has no financial interests related to his comments.

Contact Information
Rhee: 617-573-3670, DougRhee@aol.com
Robin: 410-377-2422, arobin@glaucomaexpert.com