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A phase II study investigating a novel topical cyclosporine product (CyclASol, Novaliq) formulated in a semifluorinated alkane (SFA) vehicle showed promising efficacy, safety, and tolerability. Planning is ongoing for the phase III trial of cyclosporine in the SFA technology.
Reviewed by Claus Cursiefen, MD, PhD
Topline results from a phase 2 study investigating a novel topical cyclosporine product (CyclASol, Novaliq) are encouraging about its potential to provide effective, well-tolerated immunomodulatory treatment for dry eye disease (DED).
The investigational product is a preservative-free, water-free, multidose preparation that formulates the active ingredient in a proprietary semifluorinated alkane (SFA) vehicle (EyeSol Platform Technology). The SFA vehicle itself is marketed outside of the United States as an over-the-counter ocular lubricant for lipid deficiency DED (EvoTears, Ursapharm), and it is attractive as a carrier for cyclosporine because of its ability to dissolve the lipophilic molecule and increase its stability and bioavailability.
The phase 2 multicenter, double-masked study investigated two concentrations of the novel cyclosporine-0.05% and 0.1%-and compared it with the SFA vehicle itself and cyclosporine emulsion 0.05% (Restasis, Allergan). A total of 207 patients were randomly assigned equally into the four study groups and used their assigned treatment twice daily.
Both patient groups using the investigational cyclosporine product achieved significant improvement in corneal fluorescein staining (primary endpoint) compared with vehicle over the 4-month treatment period. The greatest benefit was seen in central corneal staining. Patients using the investigational cyclosporine product also achieved symptomatic improvement.
Most noteworthy, treatment with the investigational cyclosporine formulations was associated with significant reductions in corneal and conjunctival staining by day 14 and excellent tolerability. Ninety-eight percent of patients in both investigational cyclosporine groups completed the 4-month study.
“There is a huge unmet need for a better tolerated formulation of topical cyclosporine to treat inflammation in DED. The early data from this phase 2 trial indicate that cyclosporine in the SFA vehicle may address that need, and the results also show it has the potential for rapid onset of action,” said Claus Cursiefen, MD, PhD, Chairman and Professor, Department of Ophthalmology, University of Cologne. “We look forward to the release of more data from the phase 2 trial and to these very promising results being corroborated in larger, phase 3 studies.”
Currently available topical cyclosporine products, both the 0.05% emulsion available in the United States and the 0.1% cationic emulsion (Ikervis, Santen) that is marketed in Europe, have proven efficacy for the treatment of DED based on results of the registration trials. However, discomfort on instillation, especially in the early period after treatment initiation, is a known problem for both preparations, Dr. Cursiefen told Ophthalmology Times.
“These products can cause severe symptoms, including burning, itching, and foreign body sensation, that leads to treatment cessation by a not insignificant proportion of patients,” he said.
“Formulating cyclosporine in the SFA platform, which has high biocompatibility, seems to an effective strategy for improving tolerability.”
The SFA technology also enables rapid spreading of the dispensed drop over the ocular surface without blinking, thereby minimizing spillover and enabling increased drug delivery.
Data from ex vivo studies confirm a benefit for increasing the delivery of cyclosporine into ocular tissues compared with the commercially available cyclosporine 0.05% emulsion.
“Increased bioavailability would be expected to translate into faster onset of action, and so it was interesting that in the phase 2 trial, significant improvements in ocular surface staining were achieved by day 14. In contrast, it generally takes 3 to 6 weeks to see benefit in this objective sign when using other topical cyclosporine formulations,” Dr. Cursiefen said.
Planning is ongoing for the phase 3 clinical trial program of cyclosporine in the SFA technology.
Claus Cursiefen, MD, PhD
Dr. Cursiefen is a member of Novaliq’s scientific advisory board and an advisor to Allergan and Santen.