PracticeUpdate: Dermatology - Winter 2018

CONFERENCE COVERAGE 26

Results of Two Studies Point to Potential Treatments for Alopecia Areata The selective interleukin 2/9/15 inhibitor BNZ-1 has shown promise as a therapy for alopecia areata, reports a preclinical and a clinical study presented at IID 2018.

BNZ-1 P aul Frohna, MD, PhD, PharmD, of Bioniz in Irvine, California, explained that immune pathways required for autoreactive T cell activation in alo- pecia areata have been recently proposed to involve the common γ chain cytokines interleukins 2, 9, and 15. These interleukins have been shown to be upregu- lated in animal models of alopecia areata and in human biopsies of alopecia areata lesions. BNZ-1 is a PEGylated peptide that binds to the γ chain receptor and selectively inhibits interleukin 2, 9, and 15 signaling. This inhibition shuts off the JAK-STAT/P13K/ Akt/mTOR and Raf/ERK/MAPK pathways. BNZ-1 has exhibited efficacy in reversing hair loss in a humanized mouse model of alopecia areata. BNZ-1 has undergone extensive preclinical safety testing to initiate an investigational new drug application with the FDA. BNZ1-CT-102 was a randomized, single-blind, placebo-controlled, multiple-dose study that characterized the safety, pharmacokinetics, and pharmacodynamics of intravenous BNZ-1 administered to healthy adults (n=5 per dose) once weekly at 0.5, 1, or 1.5 mg per kilogram of body weight. Overall safety was good, with no serious or severe adverse effects, infusion reactions, or dose-lim- iting toxicity observed. In all, 11 of 24 patients (46%) who received BNZ-1 experienced at least 1 adverse effect. A total of 19 adverse effects were reported. A total of 3 of 7 (43%) patients admin- istered placebo experienced at least 1 adverse effect, with 9 adverse effects reported. Adverse effects that occurred in more than 1 BNZ- 1-treated subject were sore throat, headache, and rhinorrhea. Exposure increased dose proportionally with an accumulation of approximately 40–60% and approximately 10–20% with once weekly and once every other week dosing, respectively. BNZ-1 elimination half-life was approximately 4–5 days. BNZ-1 was associated with exposure-dependent decreases in Tregs (interleukin 2), natural killer cells (interleukins 2 and 15), and CD8-positive central memory T cells (interleukin 15) as measured by flow cytometry of peripheral blood mononuclear cells. Tregs and central memory T cells reached maximum reduction at day 29. Natural killer cells dropped initially and tended to recover by day 29 except in the 1.5 mg once-weekly and 3 mg every-other-week cohorts. T cells, B cells, and monocytes were unaffected. Dr. Frohna concluded that the favorable safety and potent pharmacodynamic activity of BNZ-1 support the planned phase II trial in patients with moderate to severe alopecia areata.

Alopecia areata carries a substantial mental health burden V ivek Singam, BLA, of the Feinberg School of Medicine at Northwestern University in Chi- cago, explained that alopecia areata can be distressing psychologically and can impair quality of life. Studies of mental health comorbidities of alopecia areata, however, are limited. Dr. Singam and colleagues sought to identify men- tal health disorders and emergencies associated with alopecia areata. They examined data from the National Inpatient Sam- ple, which includes an approximately 20% sample of all US hospitalizations (n=87,053,155 admissions). They constructed multivariable logistic regression models with each mental health condition as the depend- ent variable and alopecia areata, as well as age, sex, race/ethnicity, and insurance status as independent variables. Overall, 1167 children and adults were identified with an inpatient diagnosis of alopecia areata. Alopecia areata was significantly associated with any mental health disorder (adjusted odds ratio 2.292, 95% CI 1.974–2.661). These disorders included: • Attention deficit hyperactivity disorder and conduct disorders (8.109, 95% CI 5.162–12.739) • Impulse control disorders (4.946, 95%CI 1.601–15.275) • Adjustment disorders (4.795, 95% CI 2.586–8.889) • Developmental disorders (4.345, 95% CI 2.748–6.869) • Personality disorders (3.815, 95% CI 2.282–6.370) • Suicide or intentional self-inflicted injury (2.773, 95% CI 1.659–4.634) • Substance abuse (2.585, 95% CI 1.973–3.385) • Anxiety disorders (2.456, 95% CI 1.905–3.165) • Mood disorders (2.178, 95% CI 1.805–2.628) • Psychotic disorders (2.063, 95 % CI 1.375–3.097) • History of mental health disorder or substance abuse (1.718, 95% CI 1.415–2.085) • Alcohol abuse (1.479, 95% CI 1.052–2.080) • Other mental health disorders (2.914, 95% CI 1.717–4.946) Alopecia areata was not associated with cognitive or pediatric mental health disorders. Dr. Singam concluded that strong associations were shown between alopecia areata and mental health dis- orders and emergencies in this cohort of hospitalized patients. Studies are needed to address the causes and ideal interventions for mental health disorders surround- ing alopecia areata. www.practiceupdate.com/c/68647

Dr. Paul Frohna

" …strong

associations were shown between alopecia areata and mental health disorders and emergencies in this cohort of hospitalized patients. "

PRACTICEUPDATE DERMATOLOGY