NEW ORLEANS, Louisiana — An experimental new drug for glaucoma and ocular hypertension is as effective as latanoprost but causes different adverse events, the results of a phase 3 clinical trial suggest.
Approved in Japan in 2018 and under review by the US Food and Drug Administration (FDA), omidenepag isopropyl (Eybelis) would offer an alternative for patients whose intraocular pressure (IOP) is not sufficiently lowered, or who experience side effects, from prostaglandin analogs, said Jacob Brubaker, MD, a glaucoma specialist at Sacramento Eye Consultants in Sacramento, California.
“Here, we have no pigmentation, no eyelash growth, nothing in that category, whereas with latanoprost, you see a little bit of that,” he said.
Brubaker presented the results of the PEONY trial here at the American Academy of Ophthalmology (AAO) 2021 annual meeting.
Omidenepag isopropyl’s mechanism of action is different from any other medication for glaucoma. It is hydrolyzed in the eye to its active form, omidenepag, a selective agonist for the prostanoid receptor EP2. In contrast, latanoprost acts on the FP receptor, Brubaker said.
Omidenepag increases the aqueous-humor drainage through the trabecular and uveoscleral outflow pathways, while prostaglandin analogs are thought to increase drainage through the uveoscleral outflow pathway only, according to Santen and Ube, its manufacturer and distributor.
To compare the two drugs, the researchers recruited people with open-angle glaucoma or ocular hypertension in India, Korea, Singapore, and Taiwan.
The groups were similar in age: 54.6 years for the omidenepag group, 52.6 years for the latanoprost group. The omidenepag group was 42.4% female, while the latanoprost group was 52.4% female. About two thirds of each group had a diagnosis of open-angle glaucoma, and one third had a diagnosis of ocular hypertension. Patients had used a wide variety of IOP-lowering medications before enrolling in the study.
After a washout period of 54 weeks, the researchers randomly assigned 184 people to receive omidenepag isopropyl 0.002% and 185 to receive latanoprost 0.005%. Both groups took the drops once per day.
The researchers measured the subjects’ IOP at 9:00 a.m., 1:00 p.m., and 5:00 p.m. at baseline, week 1, week 6, and month 3.
Both drugs lowered the patients’ IOPs within the first week. By the end of the third month, the latanoprost had lowered IOP slightly more, with a mean difference in diurnal IOP between the two groups of 0.64 mmHg. The difference was statistically significant (P = .0366), but its 95% CI (0.4 – 1.24) was within the margin of 1.5 mmHg that the study designers had specified to show noninferiority.
Forty percent of the people in the omidenepag group experienced adverse events, compared with 29.7% of those in the latanoprost group, and ocular adverse events affected 36.8% of the people taking omidenepag compared with 21.1% of those taking latanoprost. Ocular adverse drug reactions were higher as well with omidenepag: 23.2% vs 11.9% for latanoprost.
Drilling into this data, Brubaker noted more conjunctival hyperemia and photophobia in the omidenepag group. Two of the latanoprost patients had blepharal pigmentation, and one each had growth of eyelashes and thickening of eyelashes, compared to zero of the omidenepag patients. However, a couple of the omidenepag patients had corneal pigmentation, and none of the latanoprost patients did.
The study results did not overwhelm session moderator Luis Vasquez, MD, PhD, an assistant professor of ophthalmology at Bascom Palmer Eye Institute in Miami, Florida. “Latanoprost is a first-line therapy for most glaucoma specialists for anybody diagnosed with glaucoma,” he told Medscape Medical News. “It’s probably the most popular or most widely used medication. It’s really well tolerated. It’s safe. To beat a medication like a prostaglandin analog is a tough challenge.”
Omidenepag isopropyl didn’t meet that challenge in this study, he said. Still, it could have a role in treating glaucoma patients who don’t respond to latanoprost. Because it has a different mechanism of action, it might also be combined with prostaglandin analogs, he speculated. And he said it would be worthwhile to research whether the side effects could be reduced with lower doses.
The FDA set November 19 as the date to complete its review of omidenepag, according to Santen and Ube.
The study was funded by Santen. Brubaker reported relationships to Aerie Pharmaceuticals, Allergan/AbbVie, Equinox, Glaukos, Iridex, Ivantis, New World Medical, Nicox, and Twenty Therapeutics in addition to Santen. Vasquez has disclosed no relevant financial relationships.
American Academy of Ophthalmology (AAO) 2021 Annual Meeting: Abstract PA041. Presented November 14, 2021.
Laird Harrison writes about science, health, and culture. His work has appeared in national magazines, in newspapers, on public radio, and on websites. He is at work on a novel about alternate realities in physics. Harrison teaches writing at the Writers Grotto. Visit him at www.lairdharrison.com or follow him on Twitter: @LairdH.
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