Investigational drugs targeting prostaglandin receptors for the treatment of glaucoma

ABSTRACT

Introduction: Prostaglandin F2α analogs were the first prostaglandin agonists introduced for glaucoma treatment. Thanks to their efficacy and favorable tolerability they set a high bar in competition, with a resultant paucity in new hypotensive drug development for many years. However, the scientific community has shown recently a new interest in exploring new options for glaucoma treatment, generating a remarkable incentive in the marketplace for new drugs.

Areas covered: This article reviews agents targeting prostaglandin receptors that are currently being investigated for glaucoma treatment. We searched published literature for agonists targeting all subtypes of prostaglandin receptors found in ocular tissues. EP and FP receptor agonists are currently in the spotlight of clinical research, while less attention is paid in DP receptor agonists.

Expert opinion: Prostaglandin analogs, targeting different and combinations of receptor subtypes and compounds that exhibit additivity to commonly prescribed medications seem to be highly promising options. New treatments need to be safe, more effective, superior to existing therapies, tolerable and cost-effective. New generation compounds with multiple mechanisms of action or multiagent formulations are vigorously being investigated and generated in laboratories around the world.

KEYWORDS:

• Prostaglandin receptors
• prostaglandin analogs (PGAs)
• primary open angle glaucoma (POAG)
• intraocular pressure (IOP)
• ocular hypertension (OHT)
• aqueous humor
• trabecular meshwork
• uveoscleral tract
• omidenepag isopropyl
• latanoprostene bunod
• EP receptor agonists
• FP receptor agonists

Article highlights

• IOP remains the principal and only modifiable risk factor for glaucoma and adequate IOP control is the main mechanism to slow progression of the disease.

• A strong incentive exists for the development of novel pharmacotherapies with enhanced efficacy, longer lasting hypotensive effect and improved safety profile.

• New generation compounds with multiple mechanisms of action or multi-agent formulations are vigorously being investigated and generated in laboratories around the world.

• EP receptor agonists, particularly omidenepag isopropyl (OMDI; development code: DE-117, Santen, and Ube Industries) is showing encouraging results in upcoming phase II and III trials. In Japan, OMDI is a step before being launched in the market as it has been filed for manufacturing and marketing approval.

• ONO 9054, targeting both FP and EP3 receptors, has proven superior to latanoprost in phase II clinical trials.

• A novel FP receptor agonist with a dual mechanism of action, latanoprostene bunod, has recently gained FDA approval, adding on to available options in glaucoma treatment.

• Innovative formulations offering sustainable and adequate IOP lowering effect with less dosing requirements, as well less local side effects or even reversal of the iatrogenic inherent local toxicity of prostaglandins will be much more eagerly welcomed by patients and treating ophthalmologists.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This article was not funded.