The topical ocular hypotensive agent omidenepag isopropyl (OMDI) may be an acceptable first-line treatment and an alternative to F-prostanoid receptor agonists for patients with glaucoma and ocular hypertension, according to research published in Clinical Ophthalmology.
Although F-prostanoid receptor agonists are highly efficacious and tolerable in most patients with glaucoma and ocular hypertension, the team highlights unmet needs in this patient population. Local side effects of F-prostanoid receptor agonists may include prostaglandin-associated periorbitopathy, which comprises hyperpigmentation in the iris and around the eyelids, eyelash growth, blepharochalasis involution, periorbital fat loss, enophthalmos, deepening of the upper eyelid sulcus, and hardening of eyelids and ptosis. These side effects may impact long-term management of glaucoma, making intraocular pressure (IOP) measurements difficult, increasing ophthalmic surgical failures of trabeculectomy, and reducing treatment adherence. They also highlight that some patients do not respond to F-prostanoid receptor agonists (non-/poor responders).
After topical administration, OMDI is metabolized into omidenepag (OMD), which acts as a non-prostaglandin, selective E-prostanoid subtype 2 receptor agonist, and reduces IOP by enhancing both trabecular and uveoscleral outflow. Studies in Japan have demonstrated that topical administration of 0.002% OMDI once daily yields a 20-35% IOP-lowering effect. A direct comparison demonstrated noninferiority in lowering IOP of OMDI compared with latanoprost. OMDI was also effective and well-tolerated in patients who were non-/poor responders to F-prostanoid receptor agonists, and concomitant use of OMDI with timolol enhanced the IOP-lowering effect. As of January 11, 2022, the researchers identified 12 clinical trials registered in the US National Library of Medicine for the OMDI ophthalmic solution (DE-117), and 7 of these are phase 3 clinical trials for the 0.002% OMDI ophthalmic solution.
The safety profile of OMDI is different from those of F-prostanoid receptor agonists. Adverse events observed in patients treated with OMDI included conjunctival hyperemia, corneal thickening, macular edema/cystoid macular edema, and ocular inflammation. The researchers also note that OMDI is contraindicated in patients who are allergic to the product, in those with aphakic or pseudophakic eyes, and in those using tafluprost eye drops. Complications of prostaglandin-associated periorbitopathy have not been observed with OMDI.
The researchers explain, “If used appropriately in the right patients, OMDI could be an effective treatment option for glaucoma and [ocular hypertension] as a first-line alternative to [F-prostanoid receptor] agonists.”
Disclosure: Santen Pharmaceutical Co., Ltd. provided information on the status of clinical trials of OMDI and assisted in the preparation of figures.
Matsuo M, Matsuoka Y, Tanito M. Efficacy and patient tolerability of omidenepag isopropyl in the treatment of glaucoma and ocular hypertension. Clin Ophthalmol. 2022;16:1261-1279. Published 2022 Apr 26. doi:10.2147/OPTH.S340386