(Image credit: AdobeStock/wladimir1804)
Novaliq GmbH announced that the US Food and Drug Administration (FDA) has approved cyclosporine (Vevye) 0.1% ophthalmic solution for the treatment of the signs and symptoms of dry eye disease.
According to the company, cyclosporine ophthalmic solution, which had the development name CyclASol, is the first and only cyclosporine solution indicated for the treatment of signs and symptoms of dry eye disease with demonstrated efficacy after 4 weeks of treatment. The water-insoluble active pharmaceutical ingredient cyclosporine is solubilized in the new excipient perfluorobutylpentane. Cyclosporine ophthalmic solution is preservative-free and contains no oils or surfactants, which can be irritating and irritating to the tear film.
“We are proud that the FDA has approved VEVYE. The safety and efficacy of VEVYE were evaluated in a total of 1369 patients with dry eye disease, of whom 738 received VEVYE. VEVYE and its new vehicle were safe , well tolerated and demonstrated early, consistent and durable therapeutic effects,” said Sonja Krösser, PhD, Vice President of Medical Science and Regulatory Affairs at Novaliq, in a press release. “It’s an exciting time that you’ve followed the science that ultimately led to a new category of nonaqueous eye therapies that address unmet medical needs for patients with dry eye disease.”
John D. Sheppard, MD, MMSc, FACS, professor of ophthalmology at Eastern Virginia Medical School and Mid-Atlantic medical director for Eye Care Partners and development program investigator, said in a press release that cyclosporine ophthalmic solution addresses the well-documented underlying. inflammatory root cause of dry eye disease, repeatedly demonstrating early and clinically significant efficacy in both signs and symptoms.
“Clinical trials consistently showed significant therapeutic improvements in ocular surface damage and associated symptoms, while pioneering the analysis of improvement in visual function,” he said in a statement. “VEVYE is an exceptionally well-tolerated formulation, combining a novel first-in-class vehicle delivery system with the most established and safe topical active pharmaceutical ingredient, cyclosporine, providing a major breakthrough for our patients.”
Christian Roesky, PhD, CEO of Novaliq, praised the approval in the press release.
“The US FDA’s approval of VEVYE marks a milestone for patients and caregivers in addressing an important unmet need for millions of people living with this disease,” Roesky said in a statement. “With two EyeSol®-based, waterless dry eye drug therapies now FDA-cleared, Novaliq has established a new category of non-aqueous, non-preserved ophthalmic drugs with the opportunity to become a standard ophthalmology care in the future. We will continue to execute on our mission to transform eye therapies by developing new EyeSol® therapies well beyond dry eye disease.”
Neda Shamie, MD, a cataract, LASIK and corneal surgeon at the Maloney-Shamie Vision Institute in Los Angeles, and co-chief medical editor of Ophthalmology Times, noted that the approval was another piece of welcome news for ophthalmologists and their patients diagnosed with dry eye. illness
“The FDA approval of CyclaSol 0.1% brings us and our dry eye patients the first non-aqueous anti-inflammatory and immunomodulatory topical ophthalmic solution containing 0.1% cyclosporine,” said Shamie. The highest concentration of the active ingredient solubilized in the new excipient. perfluorobutylpentane, and has no preservatives or surfactants. This could offer a powerful anti-inflammatory treatment option aimed at treating the signs and symptoms of chronic dry eye disease.”
According to Laura M. Periman, MD, director of Dry Eye Services and Clinical Research at the Periman Eye Institute in Seattle, Washington, the immunomodulatory benefits of cyclosporine in addressing ocular surface inflammation are well established.
“However, the cyclosporine molecule is highly hydrophobic, which creates challenges with drug formulation and delivery,” he said.
Periman added that the approval now offers dry eye patients a new option for efficacy and tolerability.
“Alkanes are important in medicine and come in different configurations that impart various attributes,” he added. “Perfluorobutylpentane, the preservative-free vehicle for cyclosporine in VEVYE is unique in its ability to transport and deliver the benefits of cyclosporine to the ocular surface with an excellent safety, tolerability and efficacy profile.”
Clinical trials
In clinical trials, researchers led by Esen Akpek, MD, of the Wilmer Eye Institute, Johns Hopkins University, Baltimore, and colleagues reported clinically significant results from the use of cyclosporine topical solution at 0, 1% without water to treat patients with severe dry eye disease. The study group saw a significantly greater reduction in total corneal fluorescein staining (tCFS) score compared to vehicle.1
A treatment that provides a rapid onset of action and is well tolerated could fill an important gap in this patient population, the researchers noted.
The ESSENCE-2 study was a randomized, double-masked, vehicle-controlled clinical trial that evaluated the efficacy, safety, and tolerability of an aqueous cyclosporine ophthalmic solution. The study included 834 patients with moderate to severe DED who were randomized to active treatment (n=423) or vehicle (n=411) after a 14-day run-in period during which they instilled an artificial tear twice a day Patients instilled ciclosporin or vehicle twice daily for 29 days and the results were compared.
The study period runs from December 5, 2020 to October 8, 2021 at 27 US sites. Primary endpoints were changes in tCFS (0-15 [best to worst] on the National Eye Institute scale) and the dryness score (0-100 [best to worst] on the visual analog scale) on day 29 compared to baseline. The researchers also evaluated conjunctival staining, central corneal fluorescein staining, and tCFS responders.
ESSENCE-2 results
Patients had a mean age of 57.1 years and almost three quarters were women. Participants had a mean age of 57.1 years and 609 (73.0%) were women.
The authors reported that cyclosporine instillation provided a greater improvement in tCFS compared with vehicle, i.e., -4.0 degrees versus -3.6 degrees, respectively, on day 29, a difference that became significant (P = 0.03). The dryness score improved compared to baseline in both groups, ie -12.2 points for cyclosporine and -13.6 points for vehicle; the difference between the groups was not significant (P=0.38).
“In the cyclosporine group, 293 participants (71.6%) achieved clinically meaningful reductions of 3 grades or more in tCFS compared with 236 participants (59.7%) in the vehicle group (change, 12.6%; 95% confidence interval [CI], 6.0%-19.3%; P<0.001). These responders showed greater improvement in symptoms at day 29, including dryness (change, -4.6; 95% CI, -8.0 to -1.2; P = .007) and blurred vision (change, - 3.5; 95% CI, -6.6 to --). 4.0; P = 0.03), compared with non-responders," the researchers reported.
An important point of the study was that the total and central corneal staining score showed improvements after only 2 weeks of treatment, with persistent efficacy up to day 29. The rapid onset and magnitude of the improvements in corneal epithelial damage are potential differentiators from existing therapies, the authors emphasized.
Akpek and study investigator David Wirta, MD, presented papers at the American Society of Cataract and Refractive Surgery (ASCRS) annual meeting earlier this year in San Diego about the results of the extension study open-label 12-month ESSENCE-2 and the pooled analysis of ESSENCE-1 and ESSENCE-2, the two pivotal studies, looking at subgroups with and without cataracts.
“The long-term data confirm the excellent safety and tolerability profile of CyclASol,” Wirta said in a statement ahead of ASCRS. “Notably, all dry eye symptom scores studied showed a consistent reduction that reached a minimum after 1 year of treatment combined with high rates of patient satisfaction. If approved, this treatment will address the important needs of the patient”.
