PARIS – A first-of-its-kind Ana M. Giménez-Arnau, MD, reported at the annual congress of the European Academy of Dermatology and Venereology.
The 5% cyclosporine topical spray, known as Cyclatop, showed significantly better results across the board than its vehicle, even during the first week of treatment in the 4-week, multicenter, Spanish, double-blind, randomized, which included 44 patients with mild or moderate atopic dermatitis (AD), according to , a dermatologist at Hospital del Mar and the Autonomous University of Barcelona.
“Besides the clinical efficacy, the study also demonstrated that, when cyclosporine was detectable in the blood, the highest blood level was at least 200-fold less than after systemic administration of cyclosporine at therapeutic doses,” she noted.
The motivation to develop a topical formulation of cyclosporine stemmed from the need to find substitutes for topical corticosteroids, especially in the pediatric population, where steroid phobia is rampant among parents. And while systemic cyclosporine is approved by European regulators for treatment of difficult cases of AD and is widely utilized off label for this purpose in the United States, the fact is that it is an immunosuppressant that paints with a broad brush and is best utilized for a matter of weeks as induction therapy.
But developing a topical formulation of cyclosporine suitable for long-term use posed many challenges. Lack of stability in cream and ointment formulations was a recurring issue. “Cyclosporine is a very big molecule, which is not easy to work with topically,” she explained. “The challenge was to find a stable formulation with good skin penetration, but without systemic absorption.”
Indeed, researchers at Barcelona-based Spherium Biomed evaluated more than 100 prototype compounds in animal models before settling on a proprietary oil emulsion formulation of 5% cyclosporine delivered via a spray without propellant gas.
Key study findings
The 44 study participants had a mean baseline of 8.3% body surface area involvement. As a condition of participation, they needed to have similar lesional areas bilaterally. They treated involved areas on one side of the body twice daily with Cyclatop, while they sprayed those on the opposite side with its vehicle.
From a mean baseline Eczema Area and Severity Index (EASI) score of 5.5, EASI scores improved by an average of 3.2 points after 28 days of cyclosporine spray, compared with 1.7 points with vehicle. Atopic Dermatitis Area and Severity Index (ADSI) scores improved from a mean baseline of 6.5 by 3.6 points with topical cyclosporine versus 2.4 points with vehicle.
At week 3, an EASI 75 response – that is, at least a 75% reduction from baseline EASI scores – was achieved at 44.4% of actively treated sites, compared with 25.9% of control sites. ADSI 75 rates at 3 weeks were 33.3% and 11.1%, respectively. An Investigator’s Global Assessment of clear or almost clear was reached at week 4 at 61.5% of active treatment sites, compared with 42.3% of vehicle-treated sites.
Itching responded dramatically to topical cyclosporine. From a mean baseline score of 3.3 on a standard 10-point pruritus visual analog scale, cyclosporine spray–treated areas showed a mean 1.2-point decrease at week 4, compared with a 0.4-point reduction at vehicle-treated areas. About 50% of the reduction in pruritus scores was achieved within the first week of active treatment. Moreover, among patients with moderate as opposed to mild itching scores at baseline, who had a mean pruritus score of 5.6, topical cyclosporine spray resulted in a mean 3.3-point reduction at week 4, Dr. Giménez-Arnau continued.
No safety signals emerged in this initial study. Side effects associated with the cyclosporine spray were the same as with its vehicle, and in exit interviews, more than 85% of patients indicated they were satisfied with the comfort and practicality of topical cyclosporine.
Session chair, professor of dermatology at the University of New South Wales, Sydney, noted that the study was restricted to patients with less than 10% body surface area of involvement.
“Are you concerned that if you use this product over widespread areas, as is quite common in eczema, that you might get positive blood levels?” she asked.
“We don’t know. We should check that,” Dr. Giménez-Arnau replied. She added that more studies need to be done before cyclosporine spray is ready for the market. These studies will need to address the optimal dosing schedule and duration, the spectrum of disease severity where the topical spray works best, and other key issues.
Cyclatop is being developed by Spherium Biomed, which sponsored the study. Dr. Giménez-Arnau reported receiving research grants from and/or serving as a consultant to roughly half a dozen pharmaceutical companies.