The latest startup innovations in drugs and devices to ease the sting of dry eyes, increase opportunities for profit and pioneering a continuum of DED care.
Dry eye disease (DED) is sometimes taken as seriously as chapped lips. Yet, while 42% of eye care patients or up to 80 million Americans have complained of symptoms that indicate DED, only 16 million were ever diagnosed with DED and only 1.6 million are being treated. This means only 5-6% of the U.S. population gets any DED treatment, representing a great opportunity for DED therapeutics. “We’re in the infancy of this,” said Dr. Paul Karpecki, director of cornea services and external disease in the Kentucky Eye Institute, as he moderated the session.
Not only that, but Dr. Karpecki also said what was thought of as an elderly disease is now changing due to factors like the increasing time spent on digital devices. The Beaver Dam Offspring Study (BOSS) showed us that the prevalence of dry eye in children now matches that of their parents. Women over the age of 65 suffer from DED twice as much as men. However, there doesn’t seem to be a large statistical difference between men and women aged 21-34 when it comes to DED.
Dr. Karpecki also revealed that many specialty clinics that treat DED have been doing well with 100% return to profitability, especially during the COVID-19 pandemic. “Because their quality of life is affected, they’re more likely to come in,” he said.
With much room to make a difference, the Dry Eye Innovation Showcase (by the Ophthalmology Innovation Source) featuring eight startups gave the audience a glimpse into exciting developments in this growing area of treatment in ophthalmology. What is more fascinating is that innovations are arising from the latest understanding of the disease.
What the Market Offers
The first presentation showcased Novaliq’s unique water-free technology EyeSol® which overcomes water-based limitations in eye drops. Out of this technology, Novaliq (Heidelberg, Germany) was able to develop CyclASol®. Its Vice President of Preclinical and Clinical Development Dr. Sonja Krosser revealed CyclASol® has been able to improve cornea damage significantly over Restasis™ by reducing blurred vision and frequency of dryness. One highlight was that the trial’s subjects reported reading speed improvement with their corneal staining reduction. The technology’s increased residual time on the eye’s surface, from minutes to hours, has positive effects on its bioavailability. CyclASol® may just fill the gap of 60% of patients abandoning their treatment due to discomfort. “Its excellent tolerability profile is key for compliance,” she said.
In the area of imaging, Ra’anan Gefen, the managing director of AdOM Advanced Optical Technologies, an Israeli med-tech company, presented a singular device that comprehensively diagnoses dry eye disease. The Tear Film Imager (TFI) is currently deemed as the only device that measures muco-aqueous and lipid sublayers simultaneously in nanometer resolution. “A single 40-second automatic non-invasive test provides objective and quantified parameters,” he said. The technology was developed as a result of the understanding that mucus is a barrier for topical ophthalmic drug delivery. Besides its ability to capture measurements in 40 seconds, it has a high frame of more than 10 hertz to capture tear film dynamics (the first in the market to do so) with artificial intelligence capabilities to analyze captured images.
The Role of Therapeutics
Stepping in to combat the mucus barrier for topical ophthalmic drug delivery is Kala Pharmaceuticals (Massachusetts, USA) with its AMPPLIFY® Technology drug delivery system. Its Chief Medical Officer Dr. Kim Brazzell explained how AMPPLIFY® delivers drugs using nanoparticles with its proprietary coating to avoid interaction of the drug particles with the mucus. “In the eye, it avoids adhesion to the eye’s tear film mucins, thus enabling rapid penetration through the tear film and enhancing diffusion in the ocular tissues,” Dr. Brazzell said. Significant improvements were seen in both signs and symptoms in the same population in their four trials of this system (primary for phase 2, STRIDE 1, STRIDE 2 and secondary for STRIDE 3). Also, less than 1% reported any IOP elevation with no serious adverse events observed. AMPPLIFY® is targeted for a Q4 2020 launch with the potential to become the first-line therapy for the short-term treatment of DED, including the treatment of dry eye flares, which occur with the vast majority of dry eye patients.
OptimEyes Technologies (Ontario, Canada) sees potential in its patented platform technology using a high dose of cyclosporine. The Micelle technology comprises small polymeric spheres that are able to encapsulate drugs in their core. “Unique to our formulation, the surface of Micelles are adhesive, allowing them to bind to the ocular surface,” OptimEyes’s Chief Executive Officer Dr. Frances Lasowski said. The value Micelle proposes to bring is that it significantly reduces the dosing needed with enhanced efficacy. In animal trials comparing Micelle (0.075% cyclosporine A) with Restasis (0.05% cyclosporine A), Micelle’s dose of once every three days was equal to Restasis’ twice-daily dose. It was also shown to help tear volume and staining return to baseline.
Addressing dry eyes from a different angle, Tarsus Pharmaceuticals’ Chief Executive Officer Dr. Bobak Azamian announced its development of the first drug for Demodex blepharitis. In uncovering this disease which also causes dry eyes, Dr. Azamian also highlighted the key role that collarettes play in Demodex infestations. Collarettes are mite waste products and eggs, a pathognomonic sign of the infestation. It is found in 100% of Demodex blepharitis patients’ lashes. Dr. Azamian added that blepharitis is a large, unserved market in ophthalmology. He said that Tarsus Pharmaceuticals (California, USA) has completed four phase 2 clinical trials including randomized control trials with very strong and consistent results with phase 3 trials underway and phase 2 trials for the pipeline in 2021.
EyeDetec Medical (California, USA) President and Chief Executive Officer Dr. Barry Linder explained that dry eye is a lipid problem, and not so much a lack of tears. “Lipids prevent the evaporation from the tear film and that’s critical,” he said. Based on this, they have introduced the Eye Lipid Mobilizer (ELM), a medical device that aims to improve the eye’s oil layer and thus decrease tear evaporation and normalize the ocular surface. Combining several mechanisms, the ELM would give heat to lower the viscosity of the oil. Next, it induces resonant frequency stimulation (vibration at certain frequencies to induce liquefaction and mobilization of the oil). “Finally, there’s an activation of the lacrimal functional unit through neuromodulation to induce expression from the meibomian glands of the oil,” he explained. These would be conducted through the device worn over patients’ closed eyelids. The ELM has a strong patent portfolio, he said. EyeDetec has also to date accomplished $3 million in convertible notes with several products. The most notable is the EyeGiene® Insta-Warmth™ product, which is a reusable eye mask with single-use warming disposable vapors. The product has been validated clinically by a Singapore Eye Research Institute (SERI) published study and is a US FDA Class 1 exempt product with early sales in the United States.
What Technology Contributes
Neurostimulation influences key aspects of dry eye. Enter the iTEAR100 Neurostimulator™ from Dr. Laura Periman who is the founder and director of Dry Eye Services & Clinical Research at Periman Eye Institute (Washington, USA). The electromechanical neurostimulator device is indicated for temporary use for up to 30 days to increase tear production. Dr. Periman said, “the holy grail is the number of meibomian glands yielding liquid secretions (or MGYLS in literature)”, where the iTEAR100 was able to induce a higher yield of the clear liquid fluid in test subjects. In their 6-month trial, there was also a reported decrease in corneal staining. After the neurostimulation, although patients were advised to maintain their treatment regimen, 44% reported being able to decrease their dependence on artificial tears and a quarter of them were able to get off artificial tears altogether.
Another niche segment with potential is the diabetic dry eye market. Startup Ocunova’s Chief Executive Officer Michael Shine presented on how his company’s product OCU001 has been shown to improve corneal sensitivity, increase tear production and rapidly improve dry eye symptoms. OCU001, he said, is a novel, patented ocular dry eye treatment. This potentially unique mechanism is a corneal receptor modulator. OCU001’s multiple pre-clinical trials (animal models) have demonstrated normal tear secretions, improved corneal sensitivity and corneal surface health. Its phase 1 study has shown safety intolerance levels with a successful development through its phase 2a proof of concept trial with no serious adverse events or tolerability issues with dry eye relief experienced within two weeks. Mr. Shine said Ocunova (Pennsylvania, USA) is currently seeking investors for OCU001 in order to complete its phase 2b clinical trials.
Panel Take Home Message
The presentations were followed by Dry Eye Outlook panel featuring Dr. Karpecki and an esteemed and experienced panel of physicians, namely Dr. Whitney Hauser, Dr. Marguerite McDonald, Dr. Joseph Tauber, and Dr. William Tattler. They discussed the reasons behind the small numbers (3-5%) being treated for DED, collarettes in blepharitis, the difference between dry eye disease and meibomian gland dysfunction, the use of steroids for treating dry eyes, the current opportunity to specialize in diabetic dry eyes treatments, and the value of treating with on label therapeutics.
“There are so many causes to meibomian gland dysfunction (MGD) and dry eyes so to find one single treatment is pretty unlikely. I think there still will always going to be a poly-therapy concept. As new products come around, we’ll find new ways for them to be symbiotic together,” Dr. Hauser said.
Editor’s Note: The OIS @Dry Eye Innovation Showcase was held on 20th August 2020, 1-4 PM EDT. Reporting for this story also took place during the event.