OMLONTI- omidenepag isopropyl_solution/ drops

Omidenepag is a relatively selective EP2 receptor agonist which decreases intraocular pressure (IOP). The exact mechanism of action is unknown at this time. Elevated IOP represents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Absorption Omlonti is absorbed through the cornea where prodrug omidenepag isopropyl is hydrolyzed to become biologically active metabolite, omidenepag. After once daily ocular administration of one drop of omidenepag isopropyl 0. 0025% eye drops to both eyes in humans for 7 days, plasma concentrations of omidenepag reached C max Elimination Metabolism After topical ocular administration, omidenepag isopropyl is rapidly metabolized in the eye to omidenepag (active moiety) by carboxylesterase-1. The pharmacologically active form, omidenepag is further metabolized by liver through oxidation, N Excretion In rats, 0.

Omlonti (omidenepag isopropyl ophthalmic solution) 0. 002%, is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. 002%, is a relatively selective prostaglandin E2 (EP2) receptor agonist, indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

The recommended dosage is one drop in the affected eye(s) once daily in the evening. 1 The recommended dosage is one drop in the affected eye(s) once daily in the evening. Gently shake the bottle prior to administration. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Contact lenses should be removed prior to the administration of Omlonti, and may be reinserted 15 minutes after administration [see Patient Counseling Information (17).

The following clinically significant adverse reactions are described elsewhere in the labeling: Pigmentation [see Warnings and Precautions (5. 1) Eyelash Changes [see Warnings and Precautions (5. 2) Ocular Inflammation [see Warnings and Precautions (5. 3) Macular Edema [see Warnings and Precautions (5. 4) The most common adverse reactions with incidence >= 1% are conjunctival hyperemia (9%), photophobia (5%), vision blurred (4%), dry eye (3%), instillation site pain (3%), eye pain (2%), ocular hyperemia (2%), punctate keratitis (2%), headache (2%), eye irritation (1%), and visual impairment (1%). 1 To report SUSPECTED ADVERSE REACTIONS, contact Ocuvex at 1-877-622-9326 or FDA at 1-800-FDA-1088 or www. gov/medwatch Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Omlonti in 600 patients for up to 3 months.

Risk Summary There are no available data on the use of Omlonti in pregnant women. In animal reproduction studies, subcutaneous administration of omidenepag isopropyl to pregnant rabbits throughout the period of organogenesis produced fetal skeletal anomalies at a dose of 24 times the clinical dose, based on estimated plasma C max max (see Data Data Animal Data An embryofetal development study was conducted in pregnant rabbits administered omidenepag isopropyl once daily by subcutaneous injection at 0. 8 mg/kg/day from gestation Day 6 to 18, a period which covers implantation and the period of organogenesis in rabbits. Fetal skeletal anomalies (thoracic misaligned centrum and hemivertebra, fused sternebra, absent rib) were observed at 0. 008 mg/kg/day (24 times the maximum recommended human ocular dose [MRHOD], based on estimated plasma C max max An embryofetal development study was conducted in pregnant rats administered omidenepag isopropyl once daily by subcutaneous injection at 0. 1, or 1 mg/kg/day from gestation Day 6 to 17, to target the period of organogenesis. Omidenepag isopropyl was not found to have any effect on embryo-fetal development in rats at up to 1 mg/kg/day (2,452 times the MRHOD based on estimated plasma C max max Risk Summary There are no data on the presence of Omlonti in human milk, the effects on the breastfed infant, or the effects on milk production. However, systemic exposure to omidenepag following topical ocular administration is low [see Clinical Pharmacology (12. 3) Infertility There are no data on the effects of Omlonti on human fertility. No impairment of fertility has been reported in animals receiving omidenepag isopropyl subcutaneously at doses up to 2,452 times the clinical dose based on estimated plasma C max [see Nonclinical Toxicology (13. 1) The safety and effectiveness of Omlonti have not been established in pediatric patients. No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

NONCLINICAL TOXICOLOGY
Carcinogenesis Lifetime rodent studies have not been performed to evaluate the carcinogenic potential of omidenepag isopropyl or omidenepag. In rats dosed by subcutaneous injection daily for 26 weeks, nephroblastoma and a spermatic cord tumor were found at 0. 003 mg/kg/day (33 times the RHOD based on the estimated area under the curve [AUC]). Mammary adenocarcinoma and pituitary pars distalis adenomas were observed at 0. 03 mg/kg/day (319 fold the RHOD based on the estimated AUC). Mutagenesis Omidenepag was not mutagenic in the bacterial reverse mutation (Ames) test and the in vivo in vitro [see Clinical Pharmacology (12. 3) Impairment of Fertility In a rat fertility and early embryonic development study, daily subcutaneous doses of omidenepag isopropyl did not affect male or female fertility at doses up to 1 mg/kg/day (2,452 times the MRHOD based on estimated plasma C max The rabbit embryofetal development study administered omidenepag isopropyl to pregnant rabbits beginning on gestation day 6, covering the period of implantation [see Use in Specific Populations (8. 1) max max [see Use in Specific Populations (8. 1) Nasal cavity respiratory epithelium metaplasia was observed in cynomolgus monkeys receiving unilateral topical ocular instillations of omidenepag isopropyl at 0. 9 mcg/eye) [1. 07 fold the MRHOD, based on ocular dose comparison]. In a 13-week monkey study, the 0. 9 mcg/eye dose was associated with nasal cavity respiratory epithelial metaplasia, and increased nasal cavity goblet cell respiratory epithelium mucosa. In a 39-week monkey study, the 0. 9 mcg/eye dose was associated with increased incidence and severity of nasal cavity respiratory epithelium metaplasia. These findings were present in both the treated side and untreated contralateral side, and they were also observed in the vehicle group [see Adverse Reactions (6).
CLINICAL STUDIES
Omlonti was evaluated in three randomized and controlled clinical trials in subjects with open-angle glaucoma or ocular hypertension with average baseline IOP of 24-26 mm Hg. The double-masked treatment duration was 3 months in all 3 studies. The third study included a 9-month open-label treatment period following the 3-month double-masked treatment period. In the three studies, IOP reductions were observed for all treatment arms. In the Omlonti arm, the reduction in IOP ranged from 5-7 mm Hg across all three studies. The corresponding reductions for the timolol and latanoprost arms were 5-7 mm Hg and 6-8 mm Hg, respectively.

Ocuvex Therapeutics, Inc.

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