Effect of NFX-179 MEK inhibitor on cutaneous neurofibromas in persons with neurofibromatosis type 1.

This phase 2a trial investigated the efficacy of NFX-179 Topical Gel, a metabolically labile MEK inhibitor, in the treatment of cutaneous neurofibromas (cNFs) in neurofibromatosis type 1. Forty-eight participants were randomized to four treatment arms: NFX-179 Topical Gel 0.05%, 0.15%, and 0.5% or vehicle applied once daily to five target cNFs for 28 days. Treatment with NFX-179 Topical Gel resulted in a dose-dependent reduction in p-ERK levels in cNFs at day 28, with a 47% decrease in the 0.5% NFX-179 group compared to the vehicle (P = 0.0001). No local or systemic toxicities were observed during the treatment period, and systemic concentrations of NFX-179 remained below 1 ng/ml. In addition, 20% of cNFs treated with 0.5% NFX-179 Topical Gel showed a ≥50% reduction in volume compared to 6% in the vehicle group by ruler measurement with calculated volume (P = 0.021). Thus, NFX-179 Topical Gel demonstrated significant inhibition of MEK in cNF with excellent safety and potential therapeutic benefit.

The Use of a Novel Artificial Intelligence Platform for the Evaluation of Rhytids.

BACKGROUND: Artificial intelligence (AI) platforms are increasingly being utilized in various healthcare applications. There are few platforms that provide quantifiable assessments of dermatologic or aesthetic conditions by employing industry established scales. OBJECTIVES: The authors sought to report the results of a pilot study that evaluated the utilization and functionality of an AI engine to measure and monitor rhytids (fine lines). For this study, glabellar frown lines were employed as the clinical model. METHODS: Seventy-one patients were enrolled and monitored remotely employing current high-quality mobile phone cameras over a 14-day period. The patients were prompted to take photographs employing this platform at preset intervals, and these photographs were then rated by the AI platform and qualified raters experienced in the field of facial aesthetics. RESULTS: The AI platform had concordance with 2 qualified raters of 46% to 68%, and the inter-rater concordance between 2 rates ranged from 44% to 66%. The intra-rater concordance for the raters was between 57% and 84%, whereas the AI platform had a 100% concordance with itself. The participant and investigator satisfaction ratings of the platform were high on multiple dimensions of the platform. CONCLUSIONS: This AI platform evaluated photos on a comparable level of accuracy as the qualified raters, and it evaluated more consistently than the qualified raters. This platform may have high utility in clinical research and development, including the management of clinical trials, and efficient management of patient care at the clinical practices.

DaxibotulinumtoxinA for Injection for the Treatment of Glabellar Lines: Efficacy Results From SAKURA 3, a Large, Open-Label, Phase 3 Safety Study.

BACKGROUND: DaxibotulinumtoxinA for Injection (DAXI) is botulinum toxin Type A formulated with a novel peptide excipient. Two pivotal, single-treatment, placebo-controlled trials demonstrated efficacy and safety for moderate or severe glabellar lines. OBJECTIVE: To further evaluate DAXI in a large, open-label, repeat-treatment study. METHODS: Subjects (n = 2,691) were enrolled from the preceding pivotal trials or de novo and received 40U DAXI. Those who received repeat treatments could be retreated when they returned to baseline on the Investigator Global Assessment-Frown Wrinkle Severity (IGA-FWS) and Patient FWS (PFWS) scales at/after 12 weeks and up to 36 weeks after treatment. RESULTS: High (>96%) response rates (none or mild severity) on the IGA-FWS scale were seen after each of the 3 treatments, with peak response between Weeks 2 to 4. At Week 24, ≥32% had a response of none or mild severity. Peak response rates of ≥92% were observed at Weeks 2 to 4 on the PFWS scale. The median duration for return to moderate or severe severity was 24 weeks. The safety profile was favorable and consistent with previous trials. CONCLUSION: DaxibotulinumtoxinA for Injection efficacy was highly consistent across treatment cycles. These results confirm the previously observed efficacy rates and duration of response.

Safety and Efficacy of EB-001, a Novel Type E Botulinum Toxin, in Subjects with Glabellar Frown Lines: Results of a Phase 2, Randomized, Placebo-Controlled, Ascending-Dose Study.

BACKGROUND: Botulinum neurotoxins, which are widely used commercially for therapeutic and cosmetic applications, have historically belonged to serotypes A and B. Serotype E has a distinct profile with a faster onset and shorter duration of effect. EB-001 is a proprietary formulation of serotype E in development for aesthetic (cosmetic) and therapeutic uses. METHODS: This first-in-human, randomized, double-blinded, placebo-controlled, ascending-dose cohort study enrolled 42 subjects who received EB-001 (n = 35) or placebo (n = 7). The efficacy primary outcome was the proportion of subjects with a two-grade investigator-rated improvement in glabellar frown line severity at maximum frown. Safety evaluations included adverse events, laboratory tests, and physical examinations. RESULTS: A two-grade investigator-rated response was observed starting in the third cohort (EB-001), with increased rates observed at higher doses. Onset of clinical effect was within 24 hours, with a duration ranging between 14 and 30 days for the highest doses. Adverse event incidence was low, with the most common being mild to moderate headache. There were no serious adverse events or ptosis, and there were no clinically significant changes in other safety assessments. CONCLUSIONS: In this clinical study in glabellar frown lines, EB-001 showed favorable safety, tolerability, and dose-dependent efficacy, with an 80 percent response rate at the highest dose. The maximum clinical effect of EB-001 was seen within 24 hours and lasted between 14 and 30 days. This differentiated EB-001 profile supports its development for aesthetic and therapeutic applications where fast onset and short duration of effect are desirable. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

Clinically Relevant Reduction in Persistent Facial Erythema of Rosacea on the First Day of Treatment With Oxymetazoline Cream 1.0.

BACKGROUND: Persistent facial erythema is a clinically challenging feature of rosacea. OBJECTIVE: To evaluate persistent erythema reduction on the first day of treatment from pooled data from two pivotal trials of topical oxymetazoline cream 1.0% (oxymetazoline) in persistent facial erythema of rosacea. METHODS: In two identically designed, phase 3, multicenter trials, adults with moderate to severe persistent facial erythema of rosacea (Clinician Erythema Assessment [CEA] grade ≥3 and Subject Self-Assessment [SSA] grade ≥3) were randomized 1:1 to once-daily topical oxymetazoline or vehicle; the primary efficacy endpoint was ≥2-grade composite CEA and SSA improvement from baseline on day 29. This post hoc analysis evaluated the proportion of patients achieving ≥1-grade composite and individual CEA and SSA improvement at 1, 3, 6, 9, and 12 hours postdose on day 1 (N=885). RESULTS: Significantly more patients achieved ≥1-grade composite and individual CEA and SSA improvement with the first application of oxymetazoline than with vehicle (P less than 0.001) at all postdose time points, beginning with hour 1. Day 1 safety assessments were similar between treatments. LIMITATIONS: Short-term, post hoc analysis. CONCLUSIONS: A ≥1-grade improvement in persistent erythema achieved after the first dose of once-daily topical oxymetazoline demonstrated clinically meaningful improvement from the beginning of therapy. J Drugs Dermatol. 2018;17(6):621-626.

Novel combination regimens: biologics and acitretin for the treatment of psoriasis-- a case series.

Combination therapy has long been a mainstay of psoriasis treatment, particularly for those that suffer from moderate-to-severe disease. The biologics represent a new and exciting approach to psoriasis treatment though their use in combination regimens has not been adequately examined. This brief series reports on the combination of biologics with acitretin in the treatment of psoriasis.