Late-stage pipeline therapies that are currently in development for treating dry eye syndrome (DES) reveal that drug developers are exploring a broad set of mechanisms of action (MOAs), many of which are innovative, says GlobalData, According to the leading data and analytics company, the global sales value of the DES market was $4.0 billion in 2018 across the seven major markets (7MM*) and this is expected to grow to $14.8 billion in 2028 at a compound annual growth rate (CAGR) of 13.8%.

Vinie Varkey, Healthcare Analyst at GlobalData, comments: “Current treatment options for DES are dominated by a mix of prescription and over-the-counter (OTC) products. While Allergan’s Restasis and Novartis’ Xiidra have been in use in the US market for a while, both treatments have been associated with patient satisfaction issues such as a non-favorable tolerability profile and a slow onset of action. This gap in the market is what the late-stage pipeline therapies are currently targeting.”

Novaliq’s CyclASol is currently at the pre-registration stage with the Food and Drug Administration (FDA), following results from late-stage clinical trials that demonstrated CyclASol significantly reduced corneal and conjunctival staining, and improved ocular dryness compared with vehicle. Novaliq/Bausch + Lomb’s NOV-3 (perfluorohexyloctane) is also currently at the pre-registration stage with the FDA. As a first-in-class therapy for evaporative DES associated with meibomian gland dysfunction (MGD), late-stage trials demonstrated that NOV-03 statistically improved total corneal fluorescein staining (tCFS) and dryness score when compared to hypotonic saline eye drops.

Varkey continues: “If both of these therapies go on to win FDA approvals, Novaliq and Bausch + Lomb will likely be in a strong position to compete against the current market players. GlobalData anticipates CyclASol to be positioned as the superior cyclosporine due to its favorable tolerability profile and better bioavailability, with the potential to capture market share from other cyclosporine-based therapies. NOV-03 is also likely to be well-received by physicians and patients due to its favorable clinical and tolerability profile.”

The other late-stage pipeline therapies have shown multiple MOAs to tackle DES, with the most common approach addressing the inflammatory components of DES. For example, Aldeyra Therapeutics’s reproxalap inhibits the production of toxic metabolites that accumulate in the back of the eye. Clinical trial data was able to demonstrate a favorable profile in improving the signs and symptoms of DES including ocular dryness, ocular redness, Schirmer test, and Schirmer test responder proportions. Based on this data, the company plans to submit a new drug application (NDA) with the FDA in Q4 2022.

The stimulation of ocular surface wound healing and the cornea repair process is another approach observed among late-stage pipeline therapies. Examples of such therapies include BRIM Biotechnology’s BRM-421 and Dompe Farmaceutici’s cenegermin. Aerie Pharmaceuticals/Alcon’s AR-15512 is a TRPM8 agonist that showed statistically significant, dose-dependent improvements in tear production and Symptom Assessment Questionnaire iN Dry Eye (SANDE) score in a Phase IIb trial. TRPM8 receptors are associated with the detection of ocular surface dryness and are activated by evaporative cooling and hyperosmolarity, which can lead to tear production.

Varkey concludes: “As late-stage therapies for DES progress through clinical development, physicians and patients within this space grow increasingly excited, particularly as late-stage clinical trials are able to validate the use of therapies with new MOAs in an indication that has historically seen low levels of drug approvals.”

*7MM: US, France, Germany, Italy, Spain, UK, Japan