Psoriasis topicals continue to fill pipeline

Development of new topical therapies for psoriasis remains an area of active research that addresses an ongoing need considering that topical treatment continues to be a cornerstone of patient care, says Linda Stein Gold, M.D.

“With all of the excitement surrounding new biologics, it is sometimes overlooked that about 80% of patients with psoriasis are being managed with a topical agent, and even patients with more extensive disease use topicals to treat lesions that are resistant lesions,” says Dr. Gold, head, division of dermatology, Henry Ford Hospital, Detroit, Mich.

“Having new treatment options is important and always welcome for enabling better patient care,” he notes.

The two most recent topical product introductions are aerosol foam formulations of older drugs in novel vehicles that are cosmetically elegant and designed to enhance drug delivery.

“Traditional thinking was that drugs had to be occlusive in order to get the best penetration and efficacy. Newer vehicles demonstrate benefits that have changed our mindset, and so clinicians should not overlook the potential for changing vehicles rather than molecules to achieve better outcomes,” Dr. Stein says.

One of the new products exemplifying this concept is betamethasone dipropionate emollient spray, 0.05% (Sernivo, Promius Pharma). Unpublished data from pharmacokinetics studies demonstrate that the aerosol foam spray vehicle optimizes concentration of the active ingredient in the epidermal layers that are affected by psoriasis by promoting penetration of the corticosteroid through the epidermis and limiting its permeation into the circulation.¹

Results of a four-week head-to-head clinical trial showed the treatment success rate [clear or almost clear and at least a two-grade improvement from baseline in the Investigator’s Global Assessment (IGA)] was similar in the group randomized to betamethasone dipropionate emollient spray compared with active controls treated with augmented betamethasone dipropionate 0.05% lotion (Diprolene AF, Merck Sharp Dohme).²

“This vehicle creates a depot-like drug delivery effect. Consequently, although betamethasone dipropionate is classified as a mid-potency corticosteroid based on the vasoconstriction test, its clinical activity in this formulation is more like that of a high potency corticosteroid,” Dr. Gold says.   

A new aerosol foam formulation that is a fixed combination of calcipotriene 0.005% and betamethasone dipropionate 0.064% (Enstilar, Leo Pharma) also provides enhanced penetration and prolonged retention of its active ingredients, according to results of a study conducted in an animal model.³

Its clinical benefit was shown in a head-to-head study where significantly more patients using the fixed combination foam achieved treatment success after four weeks compared with controls who used an ointment formulation of the fixed combination, 54.6% versus 43.0%.⁴ The new foam formulation was associated with an almost identical success rate when investigated in a phase 3 study; only 4.8% of vehicle-treated controls, however, achieved treatment success.⁵

Dr. Gold notes that even with increased penetration of the corticosteroid into the skin, the fixed combination has been safe. In a maximum use study that included 35 patients with widespread disease (total body surface area 15% to 30%), there was no evidence that the fixed combination caused hypothalamic-pituitary axis suppression or adversely affected calcium homeostasis.⁶

“We know that the combination of a topical corticosteroid and a vitamin D analogue works well for improving psoriasis, and there is also evidence from preclinical and clinical studies that show topical vitamin D analogues can offset local adverse effects of corticosteroids, including skin atrophy,” Dr. Gold explains.

Topical treatment pipeline

Although topical tazarotene (0.1% and 0.05% cream and gel; Tazorac, Allergan) has an approved indication for psoriasis, the vitamin A derivative is not often used because of its potential to cause local side effects. There is evidence that adding a corticosteroid to tazarotene improves its efficacy and minimizes side effects. Now, a fixed combination of tazarotene 0.045% with halobetasol propionate 0.01% in a lotion formulation (IDP-118, Sadick Research Group) is being investigated for treatment of adults with moderate to severe plaque psoriasis in phase 3 clinical trial.   

A phosphodiesterase-4 inhibitor (AN2728, Anacor Pharmaceuticals) is also in development as a topical treatment for plaque psoriasis and for atopic dermatitis. Other nonsteroidal molecules under investigation in phase 2 trials as topical treatments for psoriasis are targeting inhibition of integrin, janus-associated kinase 1/2, tyrosine kinase and dihydrofolate reductase.

Disclosure: Dr. Gold is a consultant, investigator, and lecturer for several companies that market and/or are developing topical therapies for psoriasis.

References

1. Kircik L, Okumu F, Kandavilli S. Permeation analysis of novel steroid vehicles to deliver and retain steroid in the layers of skin associated with psoriasis. Abstract at Winter Clinical, Koloa, Hawaii, Jan 15–20, 2016.

2. Fowler JF, Hebert AA, Sugarman J. DFD-01, a novel medium potency betamethasond dipropionate 0.05% emollient spray, demonstrates similar efficacy to augmented betamethasone dipropionate 0.05% lotion for the treatment of moderate plaque psoriasis. J Drugs Dermatol. 2016;15(2):154-162.

3. Basse LH, Olesen M, Lacour J, Queille-Roussel C. Enhanced in vitro skin penetration and antipsoriatic effect of fixed combination calcipotriol plus betamethasone dipropionate in an innovative foam vehicle. J Investig Dermatol. 2014;134:S30-38.

4. Koo J J, Tyring S, Werschler WP, et al. Superior efficacy of calcipotriene and betamethasone dipropionate aerosol foam versus ointment in patients with psoriasis vulgarais – a randomized phase II study. J Dermatolog Treat. 2016;27(2):120-127.

5. Leonardi C, Bagel J, Yamauchi P, et al. Efficacy and safety of calcipotriene plus betamethasone dipropionate aerosol foam in patients with psoriasis vulgaris – a randomized phase III study (PSO-FAST). J Drugs Dermatol. 2015;14(12):1468-1477.

6. Taraska V, Tuppal R, Olesen M, et al. A novel aerosol foam formulation of calcipotriol and betamethasone has no impact on HPA axis and calcium homeostasis in subjects with extensive psoriasis vulgaris: an open, non-controlled, 8-week trial. J Drugs Dermatol. 2013;12(8):882-887.