Phase 3 Lumigan results: first report says effective, safe

Early clinical trials show the new prostamide compares well with timolol in lowering IOP.

Issue: March 1, 2001

DALLAS — Clinical investigators of Lumigan have announced the drug has proven safe and efficacious in lowering intraocular pressure in early human clinical testing.

According to presenters in a press conference held during the annual meeting of the American Academy of Ophthalmology (AAO), Lumigan (AGN 192024, Allergan) significantly lowered intraocular pressure (IOP) when compared to timolol maleate 0.5% at the 3-month point in a 12-month randomized, double-masked study. Allergan filed a new drug application for Lumigan in September and it has been accepted for a 6-month priority review by the FDA.

Lumigan belongs to a new class of IOP-lowering drugs called prostamides.

“Prostamides occur naturally in ocular tissue,” said James Brandt, MD, a clinical investigator of the drug and director of the glaucoma service at the University of California–Davis. “It is believed to be involved in the endogeneous or the intrinsic regulation of intraocular pressure in the normal eye. Lumigan represents an analogue of these compounds and as such mimics their effects internally and lowers intraocular pressure.”

Phase 3 trials

Data from the trials showed patients receiving Lumigan once a day achieved greater IOP lowering than those receiving timolol twice a day. The average IOP lowering with Lumigan was 9.2 mm Hg (35%) as compared to 6.7 mm (26%) with timolol twice a day.

To qualify for the trial, the patients had to be diagnosed with glaucoma or ocular hypertension, with an IOP between 24 mm Hg and 34 mm Hg in both eyes. Any patient who had recently had surgery or had any contraindication to beta-blockers was not allowed to participate in the study.

In all, 596 patients were randomized into three different treatment groups. The first group received Lumigan once a day, while the second received it twice a day. The third group received timolol twice a day.

There were no significant differences in patient characteristics among the groups, said Dr. Brandt. The patients averaged 62 years of age and were mostly Caucasian. Slightly less than 20% of each of the groups was African-American. Most of the patients were diagnosed with glaucoma, but a few had ocular hypertension.

According to Dr. Brandt, the once-a-day dosing regimen was more effective than both the timolol and Lumigan twice-a-day regimens. The observation that once-daily dosing of Lumigan was more effective than twice daily dosing was addressed by Larry Wheeler, PhD, Allergan’s vice president of biological sciences and new products. “The first dose results in a maximal response. The second dose is over the top of the dose-response curve,” Dr. Wheeler said.

“Baseline pressure was comparable among the groups throughout the day and was approximately 26 mm Hg at eight in the morning at baseline,” Dr. Brandt said. “Lumigan given once daily provided clinically and statistically superior pressure lowering compared with timolol at every follow-up at eight in the morning. The difference between mean pressure in the once daily group and the timolol group was 2 to 3 mm.”

Safety

According to the investigators, Lumigan proved to be safe and well-tolerated during the trials. Most adverse events were mild ocular or periocular reactions. A total of 2.6% of the patients in the Lumigan groups and 2.5% in the timolol group discontinued use due to adverse reactions.

The most common adverse results, seen in more than 5% of the Lumigan once-a-day group, were conjunctival hyperemia, eyelash growth and eye pruritus. Though the incidence of pruritus was equivalent in the timolol group, 39.7% of the Lumigan once-daily patients reported mild conjunctival hyperemia at some point during the study. Six patients in the Lumigan once-daily group had more than a mild increase in conjunctival hyperemia at month 3 of the study.

“Biomicroscopic findings show that hyperemia was present at baseline in approximately 20% of the Lumigan once-daily group,” Dr. Brandt said. “So in this case, to put it simply, randomization failed to properly distribute people with slightly red eyes among the different groups, and so there was that difference at baseline.”

For Your Information:

James D. Brandt, MD, can be reached at the University of California–Davis, Department of Ophthalmology, 4860 Y St., Ste. 2400, Sacramento, CA 95817; (916) 734-6676; fax: (916) 734-6992; e-mail: jdbrandt@ucdavis.edu. Dr. Brandt has no direct financial interest in the products mentioned in this article, nor is he a paid consultant for any companies mentioned.

Larry Wheeler, PhD, vice president of biological sciences and new products at Allergan Pharmaceuticals, can be reached at fax (714) 246-5578.