The dry eye disease (DED) market is expected to have an annual compound growth rate of 4.5% between 2017 and 2025, which should help it reach $7.7 billion by 2025. The North American market valuation by 2025 is expected to be close to $3 billion. Needless to say, at the recent OIS@AAO, the Dry Eye – Game Changer Technologies of Today and Tomorrow was a popular and timely breakfast breakout.
Moderator Kendall Donaldson, MD, along with fellow panelists Caroline Blackie, OD, PhD; Kim Brazzell, MD, PhD; Robert Kissling; Cynthia Matossian, MD; Adam Szaronos; Joseph Tauber, MD; and William Trattler, MD, noted diagnosing patients with dry eye is not necessarily difficult — but providing treatments that will “cure” the symptoms is not necessarily simple, either.
Three companies are hoping to change how clinicians manage and treat dry eye:
AxeroVision recently completely a clinical proof of concept study for its lead asset, AXR-159, and was preparing to file an IND for its second asset, AXR-270 in Q4 of 2019, said CEO and president Achim Krauss, PhD.
Pre-clinical data shows AXR-159, an integrin antagonist, not only works on the ocular surface directly but has shown a multi-point interruption of the immune cycle in DED. In a phase 2 study where the researchers identified a responder population, the drug not only impacts and benefits one area or one quadrant in the cornea but has a global impact on ocular surface staining, Dr. Krauss said. This particular integrin agonist is fast-acting as well—a substantial effect was seen after two weeks of treatment. In comparing AXR-159 data for corneal staining with data that has been previously reported for lifitegrast (Xiidra, Novartis), another integrin, the researchers found AXR-159 has similar activity but with earlier onset.
Novaliq GmbH’s non-traditional approach of treating DED centers around its 100% water-free drug-delivery technology, EyeSol, said Christian Roesky, CEO and managing director. EyeSol is the basis for two of the company’s assets in late stage clinical trials, NOV03 (perfluorohexyloctane) and CyclASol. (Editor’s note: At the end of 2019, Bausch Health acquired an exclusive license to commercialize and develop NOV03 in the U.S. and Canada.)
NOV03 is in development for the treatment of patients with evaporative dry eye with signs and symptoms driven by meibomian gland dysfunction (MGD). The drug stabilizes the lipid layer to reduce evaporation, and has the ability to penetrate the meibomian glands, Mr. Roesky said. In testing, NOV03 showed greater reduction in corneal staining at all time points when compared with saline, with the QID treatment group having greater response than the BID treatment group. Symptoms were also greatly reduced with NOV03 vs. saline, with the same dose response in the treatment groups. The researchers also analyzed their data in subgroups of patients who had used artificial tears, vs. those who hadn’t, and found no difference; the drug worked on both subgroups the same.
CyclASol is cyclosporine in the EyeSol technology. In the ESSENCE trial, CyclASol showed clinically significant improvement in both signs and symptoms from baseline as compared with a vehicle known to be active on dry eye disease.
Olympic Ophthalmics’ neuromodulation device, the ITEAR, is a drug free method used by patients at home, with fast onset of action. It’s externally applied and CEO Michael Gertner said “it’s probably easier to use than a drop after about 15 seconds of training.” A broad array of positive endpoints has been seen, reflecting the expected mechanism of action for neuromodulation, and it’s working in both aqueous tear deficiency and meibomian gland dysfunction, he added. The novelty of the product is that “it stimulates the nasolacrimal reflex from outside the nose, activating the reflex pathway.”
The TEAR1 study included a 180-day PRN phase following a 30-day static treatment phase to learn how patients would use the product in the real world, Mr. Gertner said. The study found a very high response at the beginning of the treatment period, and during the PRN phase the result is reduced as patients use the treatment less frequently. Improvement was seen in both symptoms and signs.
For Dr. Tauber, diagnosing patients with DED involves a traditional eye exam, meibography, and a study of the tears including volume and osmolarity. Dr. Blackie added “it’s not difficult to identify a dry eye patient in an advanced state of disease.” She said pre-surgical patients are the “tricky ones,” and discussed moving from a reactive to a proactive stance such as following the new ASCRS clinical guidelines about clearing up ocular surface disease prior to performing cataract or refractive surgery.
At Kala Pharmaceuticals, Dr. Brazzell said its mucus penetrating particle technology may be approved in 2020, which will help treat an underserved subset of patients. In August 2019, the company received a Complete Response Letter from the Food and Drug Administration noting it needed additional efficacy data on KPI-121, which Kala believes its STRIDE 3 study accomplishes.
“It’s good to see that we’re starting to get a bit away from anti-inflammatories,” Dr. Brazzell said. Mr. Kissling agreed (perhaps foretelling of his company’s recent acquisition of integrin agonist NOV03).
According to Dr. Trattler, more attention is being paid to the eyelid now than previously, and said BlephEx is “a great technology” that allows the clinician to take an active role in treating blepharitis through an in-office procedure. Dr. Matossian added clinicians will continue to need to evaluate other external variables, such as makeup wear, lash extensions, and permanent eyeliner, all of which can impact the tear film.
Other areas of interest included the overall reimbursement landscape and determining where in the clinicians’ armamentarium a novel drug or device may fit. Finding alternative delivery methods that are easy for patients to use will continue to be an aspect of DED management, the panelists said. Finally, for companies involved in clinical trials identifying appropriate clinical end points that will be acceptable to the FDA while still producing objective outcomes is important.