294 Berdazimer 10.3% gel, a nitric oxide-releasing topical medication for molluscum contagiosum, triggers BOTE (Beginning Of The End) inflammation and accelerates resolution

Abstract

The beginning-of-the-end “BOTE” sign describes the inflammation (with intense erythema and variable crust, pustule, scale) that predicts imminent resolution of molluscum contagiosum (MC). Posthoc analyses of 2 phase 3, 12-week, randomized, double-blind vehicle-controlled studies, B-Simple1&2, provided initial evidence that SB206 (berdazimer 10.3% gel) may trigger BOTE and shorten MC duration. We conducted a similar, larger phase 3 study, B-Simple4, and prospectively stratified patients based on baseline (BL) BOTE status (BOTE+ vs BOTE-). A pre-defined analysis of the association between the presence of BL BOTE+ lesion and MC lesion reduction including complete clearance is presented. Treatment assignment was well balanced within BL BOTE status: of 447 patients randomized to vehicle, 50.3% were BOTE+ and 49.7% were BOTE-; of 444 patients randomized to berdazimer (active), 49.3% were BOTE+ and 50.7% were BOTE-. MC lesion counts at Week 12 decreased from BL in both treatment groups at a higher level for BOTE+ vs BOTE- patients (mean±SE); vehicle arm: 44.5±4.5% BOTE+ vs 21.2±4.6% BOTE- (p<0.0001), active arm: 65.6±4.2% BOTE+ vs 59.9±4.2% BOTE- (p=0.2325). At Week 12, a similar pattern was observed for patients achieving complete clearance; vehicle arm: 56 (25.0%) BOTE+ vs 32 (14.3%) BOTE- (p=0.0043), active arm: 85 (38.8%) BOTE+ vs 59 (26.2%) BOTE- (p=0.0043). Of all patients that were BOTE- at BL, a higher proportion of patients in the active arm became BOTE+ by Week 2 vs the vehicle arm: 141 (33.8%) vs 75 (18%). Further, a higher proportion of patients failed to initiate BOTE during the study in the vehicle arm vs the active arm; 73 (16.3%) vs 33 (7.4%). Median Kaplan-Meier estimates of time to complete clearance (days) was 93 (active) vs 100 (vehicle) (p<0.0001). This study suggests that BOTE is an indicator of MC resolution and that berdazimer 10.3% gel promotes earlier BOTE initiation, resulting in faster MC resolution. ClinicalTrials.gov: NCTNCT04535531