A new era in dry eye therapy: the semifluorinated alkane-based cyclosporine A eye drop, VEVYE®
The contents of this article are informational only and are not intended to be a substitute for professional medical advice, diagnosis, or treatment recommendations. This editorial presents the views and experiences of the author and does not reflect the opinions or recommendations of the publisher of Ophthalmology 360.
By Priyanka Agarwal, PhD
Dry eye disease (DED) continues to be one of the most prevalent ocular surface disorders impacting millions of patients worldwide. While several therapeutic strategies—from artificial tears to anti-inflammatory agents—are currently available for DED therapy, effective management of this chronic disorder remains an ongoing challenge. DED is a chronic multifactorial disorder in which the different causative factors tend to augment and exacerbate each other, forming a “vicious circle.”1
Semifluorinated Alkanes: A Breakthrough Eye Drop Platform
The semifluorinated alkane (SFA) technology is a breakthrough eye drop platform that is completely devoid of water, eliminating the need for preservatives. The SFAs, perfluorobutylpentane (F4H5) and perfluorohexyloctane (F6H8), are chemically inert, non-toxic, and non-immunogenic biocompatible molecules that possess unique physicochemical properties, making them ideal carriers for ocular drug delivery and tear film stabilization.
F6H8 has been available over the counter since 2013, commercialized as EvoTears™ (Ursapharm) in Europe and as NovaTears® (AFT Pharmaceuticals) in Europe, Australia, and New Zealand. It has shown clinical efficacy in managing the signs and symptoms of dry eye disease. In the US, it is currently being marketed as MIEBO® (perfluorohexyloctane ophthalmic solution; Bausch + Lomb) to treat the signs and symptoms of DED.
Another emerging innovation in this therapeutic area is VEVYE® (cyclosporine ophthalmic solution 0.1%; Harrow Inc.), which combines the tear film stabilizing effect of SFAs with their ability to enhance ocular drug delivery of the anti-inflammatory agent cyclosporine A, which is commonly used to treat DED. VEVYE is based on F4H5 and has the potential to simultaneously target multiple underlying pathophysiologies of DED to halt its vicious circle.
The Mechanism Behind the Breakthrough of VEVYE
The distinctive feature of VEVYE is the F4H5 vehicle, which is relatively less viscous than F6H8, allowing it to spread more easily on the hydrophobic corneal surface and forming a thin hydrophobic emollient layer.2
Preclinical studies have shown a statistically significant improvement in tear lipid layer grade 30 minutes after administration of a single dose of F4H5, suggesting that F4H5 can reinforce and stabilize the tear lipid layer, potentially minimizing tear evaporation, the hallmark feature of evaporative DED. No statistically significant difference between F4H5 and F6H8 was observed up to 90 minutes after instillation.
In the longer term, both semifluorinated alkanes showed a sustained improvement in tear lipid layer grade on administration twice a day for 1 week. Again, no statistically significant difference was observed between F4H5 and F6H8 at any point during the 7-day test period, demonstrating that the ability of F4H5 to reinforce the tear film and influence the tear lipid layer grade and tear evaporation rate was comparable to that of F6H8.2
These studies explain the excellent clinical efficacy of VEVYE in the management of DED.
Clinical Impact of VEVYE in DED
Clinical studies have shown that VEVYE provides immediate relief from symptoms like burning, itching, and foreign body sensation, while also contributing to long-term improvement by stabilizing the tear film. In clinical trials, significant improvements in objective measures, such as corneal and conjunctival staining scores, were reported.3 Furthermore, in the phase 2, dose-ranging study of VEVYE, RESTASIS® (cyclosporine ophthalmic emulsion 0.05%; Allergan) was used as an open-label comparator. F4H5 alone showed no statistically significant differences compared to RESTASIS at all measured time points in both signs and symptoms.4
Most importantly, compared to other marketed cyclosporine A products, VEVYE had a faster onset of action, which has been attributed to the tear film stabilizing effects seen with F4H5 in addition to its penetration enhancing effect, which improves the local bioavailability of cyclosporine A, with the majority of treated subjects seeing clinically and statistically significant improvements by week 2.3
Beyond Relief: A Revolution in DED Management
Perhaps the most exciting aspect of VEVYE is the paradigm shift it represents in DED management. While most treatments target individual aspects of the disease, VEVYE reinforces the tear film lipid layer, potentially reducing tear evaporation and providing immediate relief while simultaneously delivering the anti-inflammatory drug cyclosporine A to address the underlying inflammatory mediators, providing a 2-pronged approach to break the vicious circle of DED.
What Does This Mean for the Future?
For years, topical eye drops have inherently been an optimal compromise between safety and efficacy. Dry eye therapies have typically focused on addressing the signs and symptoms of DED in isolation and have failed to address the multifactorial nature of chronic DED. VEVYE is among the first treatments to focus on providing immediate relief by reinforcing and stabilizing the tear film while delivering the anti-inflammatory agent cyclosporine A to address the inflammatory etiology, which plays a causal role in the manifestation of DED.
In conclusion, VEVYE embodies a disruptive innovation in the field of ophthalmology by providing optimum therapeutic efficacy without compromising safety. By offering a preservative-free, long-lasting, and safe solution to tear film instability, this SFA-based formulation provides significant improvements over conventional treatments.
As more clinicians begin to integrate VEVYE into their therapeutic arsenal, a remarkable transformation in the management and outcomes of DED will become apparent.
Priyanka Agarwal, PhD, is a pharmaceutical scientist based in the Department of Ophthalmology at The University of Auckland. Dr. Agarwal has extensive experience in translational medicine for the management of ocular surface disorders. Her PhD thesis focused on the “application of semifluorinated alkanes in dry eye therapy,” and her research has been instrumental in understanding the mechanism by which semifluorinated alkane eye drops influence ocular surface dynamics to stabilize the tear film and enhance ocular bioavailability. She is currently the Director of Research and Operations at TheiaNova Ltd. Disclosures: Dr. Agarwal is a consultant for Harrow.
References
- Baudouin C, Messmer EM, Aragona P, et al. Revisiting the vicious circle of dry eye disease: a focus on the pathophysiology of meibomian gland dysfunction. Br J Ophthalmol. 2016;100(3):300-306. doi:10.1135/bjophthalmol-2015-307415
- Agarwal P Khun D, Krösser S, et al. Preclinical studies evaluating the effect of semifluorinated alkanes on ocular surface and tear fluid dynamics. Ocul Surf. 2019;17(2):241-249. doi:10.1016/j.jtos.2019.02.010
- Sheppard JD, Wirta Dl, McLaurin E, et al. A water-free 0.1% cyclosporine A solution for treatment of dry eye disease: results of the randomized phase 2b/3 ESSENCE study. Cornea. 2021;40(10):1290-1297. doi:10.1097/ICO.0000000000002633
- Wirta D, Torkildsen GL, Moreira HR, et al. A clinical phase II study to assess the efficacy, safety, and tolerability of waterfree cyclosporine formulation for treatment of dry eye disease. Ophthalmology. 2019;126(6):792-800. doi:10.1016/j.ophtha.2019.01.024
- Agarwal P, Scherer D, Günther B, Rupenthal ID. Semifluorinated alkane based systems for enhanced corneal penetration of poorly soluble drugs. Int J Pharm. 2018;538(1):119-129. doi:10.1016/j.ijpharm.2018.01.019
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