P8436Severe HaileyeHailey disease treated with cyclosporine

Yahya Argobi, MD, Tufts Medical Center, Boston, MA, United States

Background: HaileyeHailey (gamilial benign chronic pemphigus) is a familialdisease characterized by chronic recurrent macerated plaques and erosions. It isan autosomal dominant disease caused by a genetic defect in a calcium ATPase(ATP2C1). It usually manifests in early twenties by bullous and vesicular dermatitison the intertriginous areas. It can be localized or widespread and secondarilyinfected.

Case report: We are reporting a severe case of HaileyeHailey disease responding tocyclosporine. The patient has HaileyeHailey for[20 years, failed topical steroids,Carac, systemic antibiotics, Accutane, Soriatane, prednisone, and Enbrel. Patientreported good result with cyclosporine and 50% of the lesions cleared up within thefirst month of cyclosporine.

Conclusion: In conclusion, cyclosporine could be helpful in control of severerecalcitrant HaileyeHailey disease.

AB88

cial support: None identified.

Commer

P8402Unusual large deletion of ABHD5 gene responsible of DorfmaneChanarinsyndrome in a Moroccan patient

Benjamin Roussel, Li2P EA4222, Bobigny, France; Catherine Prost-Squarcioni,MD, PhD, Laboratory of Histology, Bobigny, France; Felipe Nery, MD, Departmentof Hepatology, Clichy, France; Frederic Caux, MD, PhD, Li2P EA4222, Bobigny,France; Liliane Laroche, MD, PhD, Department of Dermatology, Bobigny, France;Olivier Schischmanoff, PhD, Laboratory of Biochemistry, Bobigny, France

DorfmaneChanarin syndrome (DCS) is a rare recessive storage disease character-ized by nonbullous congenital ichthyosiform erythroderma (NCIE), liver steatosis,cataract, and deafness. DCS is associated with diffuse intracellular accumulation oftriglycerides related to mutation of a 7 exons gene, ABHD5. We report a new DCSpatient with an original alteration of ABHD5. A 16-year-old Moroccan male bornfrom a consanguineousmarriage presentedwith NCIE. Family history revealed that amaternal cousin had NCIE. Skin examination showed NCIE with diffuse fine greyscales, dark grey scales on the knees, elbows and dorsal aspect of the hands andbilateral ectropion. Ocular examination found small lens opacities. Numerouscytoplasmic lipid droplets were seen in leukocytes on blood smears. Blood testsrevealed raised ASAT, ALAT, ALP, CK, and LDH levels. Liver biopsy demonstratedsteatohepatitis and centrilobular and septal fibrosis without cirrhosis. Cutaneousbiopsy revealed mild acanthosis, orthokeratotic hyperkeratosis and areas ofparakeratosis. Electron microscopy of skin showed cytoplasmic large vacuoles inkeratinocytes, melanocytes, fibroblasts, mastocytes, and smooth myocytes, in favorof typical DCS. Analysis of patient ABHD5 mRNA demonstrated no amplicon by RT-PCR using primers covering the complete transcript and by RT-qPCR. PCR andsequencing using genomic DNA revealed normal exons 3 to 7 but no amplicons forexons 1 and 2. A large genomic deletion was suspected. To evaluate the borders ofthis deletion, we designed regularly distributed primer pairs from intron 2 to -40,391bp before the start codon of ABHD5. The limits of the deletion are in progress butthey were around between the middle of intron 2 and -7,079 bp before the ATG,suggesting the deletion is approximatively 13,000 bp. Currently, 32 mutations ofABHD5 have been reported including only 2 deletions. The first removed 1,058 bpand the second 1,487 bp, both at the distal part of the gene. To date, the deletion ofour patient is the largest described in the literature. It deletes the promoter region ofABHD5 and it is noteworthy that complete absence of ABHD5 expression results in atypical DCS phenotype similar to other DCS patients with point mutations. Insummary, we reported a novel case of DCS presenting a large deletion of ABHD5.Dermatologists have to be aware of DCS diagnosis, to be confirmed by blood smearsand ABHD5 analysis and to detect systemic involvement of this serious disorder.

cial support: None identified.

Commer

J AM ACAD DERMATOL

HAIR AND NAIL DISORDERS

P8213A blinded review of the ongoing SOLUTION study, a phase 2b/3 study of 2dosing regimens of a novel 10% luliconazole solution in patients withonychomycosis

Linda Stein, MD, Henry Ford Health Systems, Detroit, MI, United States; AmirTavakkol, PhD, Topica Pharmaceuticals, Inc, Los Altos, CA, United States; HectorWiltz, MD, FXM Research Corp, Miami, FL, United States; Michael Noss, MD,Radiant Research, Inc, Cincinnati, OH, United States; Richard Pollak, DPM, MS,Endeavor Clinical Trials, San Antonio, TX, United States; Steve Kempers, MD,Minnesota Clinical Study Center, Fridley, Minnesota, United States

Background: Luliconazole is a novel imidazole, and one of the most potent antifungalagents against Trichophyton rubrum and Trichophyton mentagrophytes. It ismarketed as 1% cream and 1% solution in Japan for the treatment of superficialmycosis of skin.A10%luliconazole solution (LS) isbeingdeveloped foronychomycosis(OM). In in vitro and in vivo studies, LS is shown to fully penetrate and exhibit potentactivity in healthy and fungus infected human toenail models. In addition, in a phase 1PK and safety trial LS exhibited low systemic absorption and high nail bioavailability inpatients with moderate to severe OM. A phase 2b/3 dose-finding trial is beingconducted to assess efficacy and safety of this novel formulation in OM patients.

Methods: Subjects, 18-70 years old of any sex and race have been randomized into 4groups in the US. The first treatment regimen is once a day application for 48 weeks,and the second is a once a day application for 12 weeks followed by once weeklyapplication for 36 weeks, and 2 matching vehicle arms (2:2:1:1). Subjects hadclinical diagnosis of mild to moderate distal subungual OM, affecting 25% to 50% ofthe nail, and a positive KOH and positive culture. Before subject enrollment, targettoenail screening photographswere reviewed by an independent review committeeof 3 OM experts for adherence to specific protocol entry criteria. All subjects will befollowed for an additional 4 weeks off drug to assess the primary endpoint ofcomplete cure at week 52. An IRB approved ClinCard program was implemented toprovide subjects with text reminders and educational messages to enhanceretention and compliance with protocol.

Results: Three hundred thirty-four patients have been randomized with 50% havingcompleted 6 months of treatment. Currently, across study visits, all the tolerabilityassessments have indicated no clinically significant findings or AEs. There has beenno pattern of laboratory changes and no serious AE events related to the LS studymedication. We will present demographics, baseline characteristics including age,sex, and race; percent nail involvement; nail thickness at entry; and otherinformation. In addition, aggregate, blinded local tolerability, safety data andcomparative susceptibility testing of OM clinical isolates will be presented.

Conclusions: Luliconazole solution 10% is well tolerated by all subjects. Enrolledsubjects have disease severity and demographics similar to recently reported OMtrials.

d by Topica Pharmaceuticals.

Supporte

P8592An innovative terbinafine transungual solution (P-3058): A phase 2b dosefinding study in patients with mild to moderate onychomycosis

Robert Baran, MD, Dermatology, Nail Disease Centre, Cannes, France; FedericoMailland, MD, Polichem SA, Lugano, Switzerland; Linda Frisenda, ScD, PolichemSA, Lugano, Switzerland; Maurizio Caserini, MD, Polichem SA, Lugano, Switzerland

P-3058, an innovative transungual solution containing terbinafine HCl as activeingredient and the novel excipient hydroxypropyl chitosan as film-forming agent,has been developed for the topical treatment of onychomycosis. Mild to moderateonychomycosis patients (25-60% nail involvement, matrix uninvolved) were ran-domized to receive 1 out of 5 treatment arms for 52 weeks: P-3058 5% and 10% o.d.,P-3058 10% o.w., vehicle o.d.or o.w. in a phase 2b dose finding, multicenter,randomized, double blind, vehicle controlled, parallel-group study. Primaryendpoint was responder rate at 6-month follow up. Secondary endpoints werecomplete cure, mycological outcomes, safety, and local tolerability. Overall, 588were randomized and 370 patients were included in the efficacy analysis: 93 (25.2%)in 10% o.d., 94 (25.4%) in 5% o.d., 91 (24.5%) in 10% o.w., and 92 (24.9%) in thevehicle group. Demographic and baseline characteristics were homogenous amongall treatment groups. Patients were predominantly female (60%) and at baseline, theaffected target toenail area was in average 40.7% with overall 6 affected nails. Theresponder and cure rates with P-3058 o.w. was definitely clinically relevant being23.08% and 10.99% achieved after 3 months of follow-up andmaintained for another3months. Subgroup analysis suggests that age (70) and severity at baseline (50%) areimportant prognostic factors increasing the responder and cure rates up to 26.7%and 12%, respectively. The largest proportion of conversion to negative wasachieved, as expected, by the highest dose regimen, P-3058 10% o.d. (68.82% atweek 64 and 72.13% at week 76). A higher rate of negative culture was recorded inall groups along treatment course and follow-up. Nevertheless, the differenceamong groups was statistically significant at almost all time points during treatment.As expected, no drug-related adverse events were reported for all treatment groups.No difference in vital signs and clinical chemistry occurred. In particular, no signs ofhepatotoxicity were noticed. Local irritation was recorded very rarely (0.01%)during the treatment. Results of this study show that P-3058 10% o.w. is efficaciousfor topical treatment of onychomycosis. Despite the limited sample size of this phase2b, a trend of superiority versus vehicle was evident. Statistical significance wouldhave been achieved 3 months after end of treatment, slightly increasing the samplesize from 92 to 123 per treatment group.

d 100% by Polichem SA.

Sponsore

MAY 2014