Evaluation of a First-in-Class Proteasome Inhibitor in Patients With Moderate to Severe Rosacea

June 2021 | Volume 20 | Issue 6 | Original Article | 660 | Copyright © June 2021


Published online May 28, 2021

J. Mark Jackson MDa, Rick Coulon b, Jack L. Arbiser MD PhDc

aUniversity of Louisville, Division of Dermatology, Louisville, KY
bForefront Dermatology, Louisville, KY
cDepartment of Dermatology, Emory University School of Medicine; Accuitis LLC, Atlanta, GA;
Atlanta Veterans Administration Medical Center, Atlanta, GA; Winship Cancer Institute of Emory University; Atlanta, GA

Abstract
Background: Novel, effective, affordable therapies for rosacea are needed. Innovative methods of assessing response for rosacea treatments are needed as well. This trial was designed to evaluate efficacy and safety of ACU-D1, a novel inhibitor of the 26S protea-some for the treatment of moderate to severe rosacea in a first in human pilot study. In addition, this is the first trial to our knowledge to use Canfield imaging to quantitatively assess responses.
Methods: This was a 14-week, randomized, double-blinded, placebo-controlled study, performed at two well established rosacea clini-cal trial sites, which randomized 40 adult subjects with moderate to severe rosacea (Investigator’s Global Assessment [IGA]=3/4) to either ACU-D1 (27) or comparator vehicle (13) twice daily. In addition, Canfield imaging was used to assess responses both qualitatively and quantitatively
Results: A total of 39 subjects participated, with 38 completing the study. ACU-D1 displayed efficacy in 92% (25 of 27) of patients in reducing inflammatory lesions and a 2 plus grade IGA reduction of clear to near clear in 27% of patients. There was a trend toward improvement in erythema as well in the active arm.
Conclusion: This study demonstrates that topical ACU-D1 is safe and well-tolerated by patients in the study and demonstrates efficacy in reducing inflammatory lesions and erythema in patients with rosacea. Improvement was also noted on Canfield imaging, and this modality is likely to be used as an objective measure in the future. Further studies are warranted based on these initial positive results.
ClinicalTrials.gov Identifier: NCT03064438

J Drugs Dermatol. 2021;20(6):660-664. doi:10.36849/JDD.5925

INTRODUCTION

Rosacea is a common inflammatory disorder of the facial skin and eyes. It is a disease that may progress with age, and has previously been associated epidemiologically with Northern European descent and environmental factors including dietary factors, alcohol, photo damage, and neurologic stressors.1-3 Rosacea is being increasingly recognized in East Asia as well4 and may occur in patient with darker skin types. From an inflammatory standpoint, it shares some features with acne vulgaris, but tends to affect an older population.5 Clinically, rosacea has traditionally been subdivided into four subtypes. Type 1 rosacea is the most common and is characterized by facial erythema. Type 2 is usually more severe than type 1 and is characterized by papules and pustules. Type 3 is known as rhinophymatous rosacea and may represent the endpoint of chronic type 1 and type 2 rosacea and is often disfiguring. Type 4 rosacea involves the eyes, and is commonly treated concurrently with topical agents and with oral antibiotics such as doxycycline.6 Most patients manifest with more than one subtype and we are moving more to a phenotypic description of the disease.

There is an unmet need for rosacea treatments and especially ones that target more than one manifestation. The most common therapies include topical metronidazole, azelaic acid, ivermectin, and vasoconstrictors such as brimonidine, as well as oral tetracyclines.3,7-9 Each of these treatments is complicated by factors such as low efficacy, rebound, antibiotic resistance, and high pricing for drugs with modest efficacy. Oral antibiotics for non-infectious disorders are coming under increasing scrutiny due to newly discovered effects on the gut and skin microbiome.2 Thus, there is a pressing need for novel therapies for rosacea that impact all components of the disease.

In this report, we evaluate the efficacy and safety of ACU-D1 (Pentaerythritol tetrakis (3-(3, 5-di-tert-butyl-4-hydroxyphenyl) propionate), a novel proteasome inhibitor in a first in human