Dry eye syndrome (DES) is an indication whose mainstay treatment has been dominated by Allergan’s Restasis (cyclosporine ophthalmic emulsion 0.05%) ever since its launch in 2003 in the US. While a handful of therapies have launched since then, late-stage pipeline therapies that are currently in development reveal that drug developers are exploring a broad set of mechanisms of action (MOAs), many of which are innovative, to tackle DES.

Current treatment options for DES are dominated by a mix of prescription and over-the-counter (OTC) products. Competing against Restasis are Novartis’ Xiidra (lifitegrast ophthalmic solution 5%), which launched in the US in 2016, and Sun Pharma’s Cequa (cyclosporine ophthalmic solution 0.09%), which launched in the US in 2019. While both of these therapies compete directly against Restasis, Kala Pharmaceuticals’ Eysuvis (loteprednol etabonate suspension 0.25%), which was sold to Alcon in July 2022, is a corticosteroid used for short term treatment of the signs and symptoms of DES. Artificial tears are also used extensively in conjunction with prescription therapies for symptomatic relief. While Restasis and Xiidra have been in use in the US market for a long time, 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 (0.1% cyclosporine A) is currently at pre-registration stage with the 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 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. 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. The most common approach is to address the inflammatory components of DES. For example, Aldeyra Therapeutics’ reproxalap inhibits the production of toxic metabolites that accumulate in the back of the eye. Clinical trial data were 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 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.

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.