Scalp psoriasis affects most patients with psoriasis but can be difficult to treat. To evaluate efficacy and safety of once-daily roflumilast foam 0.3% on scalp and body psoriasis. In a phase 2b, randomized controlled trial, adults and adolescents ≥12 years old with scalp and body psoriasis were randomized (2:1) to roflumilast foam 0.3% or vehicle for 8 weeks. The primary efficacy endpoint was scalp-Investigator Global Assessment (IGA) Success (score of Clear or Almost Clear plus 2-grade improvement from baseline) at Week 8. Safety and tolerability were also evaluated. Significantly more roflumilast-treated patients (59.1%) than vehicle-treated patients (11.4%) achieved scalp-IGA Success at Week 8 (P < 0.0001); differences favored roflumilast as early as the first postbaseline visit at Week 2 (P = 0.0009). Significant improvements also occurred for secondary endpoints, including body-IGA Success, Scalp Itch-Numeric Rating Scale, and Psoriasis Scalp Severity Index. The safety of roflumilast was generally similar to vehicle. Patients treated with roflumilast experienced low rates of treatment-emergent adverse events (AEs) with few discontinuations due to an AE. Few patients from skin of color backgrounds (11% non-White) and adolescents (0.7%) were included. These results support further development of roflumilast foam for treating scalp and body psoriasis. NCT04128007.

Gusacitinib is an oral inhibitor of Janus and Spleen tyrosine kinases. The efficacy and safety of gusacitinib were evaluated in a double-blind, placebo-controlled, multicenter, phase 2 study in 97 chronic hand eczema patients randomized (1:1:1) to placebo or gusacitinib (40 or 80mg) for 12weeks (part A). Then, in part B (through week 32), the patients received gusacitinib. At week 16, patients receiving 80mg gusacitinib showed a 69.5% (P <.005) decrease in the modified total lesion-symptom score versus 49.0% for 40mg(P =.132), and 33.5% for placebo. Considerable improvement in Physician's Global Assessment was seen in 31.3% of patients receiving 80mg versus 6.3% of placebo (P <.05). A 73.3% decrease in the hand eczema severity index versus placebo (21.7%) occurred in patients receiving 80mg(P <.001). Patients receiving 80mg experienced a considerable decrease in hand pain (P <.05). As early as week 2, considerable reductions over placebo in modified total lesion-symptom score (P <.005), Physician's Global Assessment (P =.04), and hand eczema severity index (P <.01) were observed (80mg gusacitinib). Adverse events included upper respiratory infection, headache, nausea, and nasopharyngitis. Gusacitinib showed rapid improvement in chronic hand eczema patients and was well tolerated, warranting further investigations.

BackgroundTherapies for children with atopic dermatitis (AD) have safety and tolerability concerns that may limit long-term use. Ruxolitinib cream, a Janus kinase (JAK) inhibitor, is effective and well tolerated in adolescents and adults with AD. ObjectiveTo analyze the safety and tolerability of ruxolitinib cream in pediatric patients. Pharmacokinetics and efficacy were also evaluated in this phase 1 study (NCT03257644). MethodsPatients aged 2 to 17 years with AD (affected body surface area 8%-20%; Investigator's Global Assessment score ≥2) were enrolled stepwise in 6 age-descending, strength-increasing cohorts to apply 0.5%, 0.75%, or 1.5% ruxolitinib cream twice daily for 28 days. Safety, pharmacokinetics, and efficacy were analyzed at baseline, week 2 (day 10), and week 4 (day 29). ResultsAmong 71 patients, 44 (62.0%) had a baseline Investigator's Global Assessment score of 3; median (range) body surface area affected at baseline was 12.2% (1.7%-20.4%). Ruxolitinib cream was well tolerated, with 4 patients (5.6%) experiencing treatment-related adverse events (all grades 1/2). No clinically meaningful changes in mean chemistry or hematology values were observed, and no consistent pattern of change in bone biomarkers was detected. Mean plasma ruxolitinib levels within each cohort (range, 23.1-97.9 nM) were well below the half-maximal inhibitory concentration for thrombopoietin phosphorylation of STAT3 (281 nM). All cohorts experienced improvements in exploratory efficacy end points. ConclusionRuxolitinib cream was well tolerated in pediatric patients with AD, with no effect on blood counts or bone biomarkers. Mean plasma concentration was low. Efficacy was consistent with data from previous studies in adolescents and adults. Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT03257644

Interleukin 17C (IL-17C) modulates epithelial inflammation and has a possible role in atopic dermatitis (AD) pathology. Four randomized clinical studies (Phase 1 and 2) investigated the safety, tolerability, efficacy, and pharmacokinetic profile of the anti-IL-17C monoclonal antibody MOR106 for up to 12 weeks (NCT03568071: n = 207 adults with moderate-severe AD; NCT03689829 Part 1: n = 32 healthy males; NCT03689829 Part 2: n = 44 adults with moderate-severe AD; and NCT03864627: n = 76 adults with moderate-severe AD). In these studies, MOR106 was either administered intravenously (i.v.) every 2 or 4 weeks at doses between 1-10 mg/kg, or subcutaneously (s.c.), either as a single dose or doses every 2 weeks at 320 mg. Overall, MOR106 was well-tolerated, and the safety profile was consistent with monoclonal antibodies approved for AD. Bioavailability following s.c. dosing was 55%, and steady-state drug levels were reached at 2-4 weeks. Ongoing studies were terminated following a futility analysis of the Phase 2 placebo-controlled dose-finding study (NCT03568071) due to a low probability for achieving the primary efficacy endpoint. Cumulatively, MOR106 demonstrated ineffectiveness for the treatment of AD, but its safety and pharmacokinetic characteristics warrant further drug development in other indications. Funding: sponsored by Galapagos NV; funded by Novartis AG.

BackgroundRuxolitinib cream is a topical formulation of ruxolitinib, an inhibitor of Janus kinase 1 and Janus kinase 2.ObjectiveWe aimed to determine the safety, tolerability, and bioavailability of 1.5% ruxolitinib cream under maximum-use conditions in patients with atopic dermatitis. Efficacy was evaluated as an exploratory objective.MethodsEligible patients aged ≥ 12–65 years with atopic dermatitis, an Investigator’s Global Assessment score ≥ 2, and ≥ 25% affected body surface area were enrolled in an open-label, maximum-use phase I study conducted in the USA and Canada. Patients applied 1.5% ruxolitinib cream twice daily to lesions identified at baseline for the first 28 days and continued use only on active lesions for an additional 28 days (extension period). Safety was assessed by frequency, duration, and severity of treatment-emergent adverse events. Plasma concentrations of ruxolitinib and pharmacokinetic parameters were assessed as secondary endpoints.ResultsOverall, 41 patients (median age, 17 years; 51% male) were enrolled and 37 (90.2%) entered the extension period, all of whom completed the study. Treatment-emergent adverse events were reported in 13 patients (31.7%). Treatment-related adverse events were reported in four patients (9.8%). The mean (standard deviation) steady-state plasma concentration was 104 (309) nM during the first 28 days, well below the half-maximal inhibitory concentration of Janus kinase-mediated myelosuppression in the bone marrow (281 nM), and decreased further during the extension period. Higher plasma concentrations were detected in a few patients who were treated for a very high affected body surface area. At day 56, 94.6% of patients achieved ≥ 75% improvement in the Eczema Area and Severity Index.ConclusionsUnder maximum-use conditions, ruxolitinib cream was generally well tolerated, with approximately one-third of patients experiencing treatment-emergent adverse events and few treatment-related adverse events. The mean steady-state plasma concentration of ruxolitinib was well below the level expected to affect bone marrow production of blood cells, with a small number of patients exhibiting higher plasma concentrations. In addition, ruxolitinib cream showed a high level of efficacy in patients with atopic dermatitis involving ≥ 25% affected body surface area.ClinicalTrials.gov IdentifierNCT03920852.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-022-00690-3.

BackgroundTapinarof is a novel topical therapeutic aryl hydrocarbon receptor modulating agent in development for the treatment of psoriasis and atopic dermatitis.ObjectiveThis multicenter, open-label trial assessed the safety, tolerability, pharmacokinetics (PK), and efficacy of tapinarof cream 1% once daily (QD) under maximal use conditions in extensive plaque psoriasis.MethodsAdults with a baseline Physician Global Assessment (PGA) score of ≥ 3 and body surface area (BSA) involvement ≥ 20% received tapinarof cream 1% QD for 29 days. Safety and tolerability assessments included adverse events (AEs) and local tolerability scales. PK parameters were calculated using non-compartmental analysis. Efficacy assessments included change in PGA, Psoriasis Area and Severity Index score, and %BSA affected.ResultsTwenty-one patients were enrolled. Common AEs were folliculitis, headache, back pain, and pruritus (none led to discontinuation). Tapinarof plasma exposure was low, with the majority of concentrations being below detectable limits. At day 29, 14 patients (73.7%) had a ≥ 1-grade improvement in PGA score and six patients (31.6%) had a ≥ 2-grade improvement; four patients (21.1%) achieved treatment success (PGA 0 or 1 and ≥ 2-grade improvement).ConclusionTapinarof cream 1% QD was well tolerated, with limited systemic exposure and significant efficacy at 4 weeks in patients with extensive plaque psoriasis.ClinicalTrials.gov Identifier NCT04042103.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40257-021-00641-4.

Objectives: The Vaginal pH Modulator (VPM; PhexxiⓇ) is a vaginal gel of lactic acid, citric acid, and potassium bitartrate, which maintains an acidic environment even in the presence of alkaline semen. VPM was recently approved for prevention of pregnancy. The objective of the current analysis is to report pooled safety data from the two pivotal phase 3 studies (AMPOWER and AMP001).

Atopic dermatitis (AD) affects ∼10%–20% of children and ∼5%–10% of adults worldwide, with rates varying geographically. Here, medical history including prior therapy at screening in adolescent and adult patients enrolled in two randomized phase 3 studies of ruxolitinib cream for patients with AD (TRuE-AD1 [NCT03745638], TRuE-AD2 [NCT03745651]) is reported to assess disease burden in this population.

Abstract not available.