CO9 - Efficacy and Safety of Brepocitinib in Patients with Cutaneous Sarcoidosis: Results from a Randomized, Double-Blind, Multicenter, Placebo-Controlled, Phase II (BEACON) Trial
Misha Rosenbach (United States)1; Bridget Shields (United States)2; Margaret Coates (United States)3; Ogugua Ndili Obi (United States)4; Anne L. Marano (United States)5; Aaron Mangold (United States)6; Oluwakemi Onajin (United States)7; Anna Haemel (United States)8; David Fivenson (United States)9; Daniel A. Culver (United States)10; Marc A. Judson (United States)11; Claire Hannah (United States)1; Craig Smuda (United States)7; Samantha Polly (United States)5; Rashmi Unwala (United States)12; Logan Harper (United States)10; Manuel Ribeiro Neto (United States)10; Paras Vakharia (United States)13; Cuong Nguyen (United States)13; Galen Foulke (United States)14; Matthew Helm (United States)14; Sylvia Hsu (United States)15; Rohit Gupta (United States)15; Donna A. Culton (United States)3; Robert Pariser (United States)16; Jordan Talia (United States)17; Katharina S. Shaw (United States)18; Brendan Johnson (United States)18; Lauren Graham (United States)19; Joseph Barney (United States)20; Sotonye Imadojemu (United States)21; Avrom S. Caplan (United States)22; William Damsky (United States)23;
1 - Department of Dermatology, Perelman School of Medicine, Philadelphia, Pennsylvania; 2 - Department of Dermatology, The School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin; 3 - Department of Dermatology, The University of North Carolina Chapel Hill, Chapel Hill, North Carolina; 4 - Department of Internal Medicine, East Carolina University, Greenville, North Carolina; 5 - Department of Dermatology, Duke University School of Medicine, Durham, North Carolina; 6 - Department of Dermatology, Mayo Clinic, Scottsdale, Arizona; 7 - Division of Biological Sciences, University of Chicago, Chicago, Illinois; 8 - Department of Dermatology, University of California San Francisco School of Medicine, San Francisco, California; 9 - Fivenson Dermatology, Ann Arbor, Michigan; 10 - Department of Pulmonary Medicine, Cleveland Clinic, Cleveland, Ohio; 11 - Pulmonary & Critical Care Medicine, Albany Med Health System, Albany, New York; 12 - Department of Dermatology, Cleveland Clinic, Cleveland, Ohio; 13 - Department of Dermatology, Feinberg School of Medicine, Northwestern Medicine, Chicago, Illinois; 14 - Department of Dermatology, PennState College of Medicine, Hershey, Pennsylvania; 15 - Department of Dermatology, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania; 16 - Pariser Dermatology, Norfolk, Virginia; 17 - Kimberly and Eric J. Waldman Department of Dermatology at Mount Sinai, New York City, New York; 18 - Priovant Therapeutics, Durham, North Carolina; 19 - Department of Dermatology, The University of Alabama at Birmingham, Birmingham, Alabama; 20 - Department of Pulmonary, Allergy, & Critical Care Medicine, The University of Alabama at Birmingham, Birmingham, Alabama; 21 - Department of Dermatology, Brigham and Women's Hospital, Boston, Massachusetts; 22 - Ronald O. Perelman Department of Dermatology, New York University Grossman School of Medicine, New York City, New York; 23 - Department of Dermatology, Yale School of Medicine, New Haven, Connecticut;
Keywords: Cutaneous Sarcoidosis; Randomized, Placebo-Controlled Clinical Trial; Brepocitinib;
Select the theme: Special Topics in Extrathoracic Sarcoidosis
Type: Original Papers
Presentation: Oral Communication
Introduction: Cutaneous sarcoidosis (CS) is a chronic, serious condition with no approved therapies. Proinflammatory cytokines signaling through TYK2 and JAK1 are implicated in its pathogenesis.
Objectives: To evaluate the efficacy and safety of two doses of brepocitinib, an oral TYK2/JAK1 inhibitor, in adults with CS.
Materials and Methods: BEACON (NCT06978725) was a multicenter, randomized, double-blind, placebo-controlled trial enrolling adults with active CS (Cutaneous Sarcoidosis Activity and Morphology Instrument-Activity [CSAMI-A] ≥10). Participants were randomized 3:2:2 to brepocitinib 45mg, brepocitinib 15mg, or placebo once daily for 16 weeks, with continuation of stable background therapies. For participants receiving oral corticosteroids (OCS) at baseline, a mandatory taper was implemented. The primary endpoint was change from baseline in CSAMI-A at Week 16 (minimal clinically important difference: ≥5-point reduction). Secondary endpoints included achievement of “Clear”/“Almost Clear” on Investigator’s Global Assessment (CSA-IGA), functional skin remission (CSAMI-A <5), patient-reported outcomes, and safety.
Results: Thirty-one participants (58% female; mean age, 53.3 years) with highly active disease (mean [SD] CSAMI-A, 33.6 [17.6]) were enrolled. Brepocitinib 45mg significantly improved CS disease activity, separating from placebo by Week 4 and achieving a mean CSAMI-A reduction of 22.3 points at Week 16 versus 0.7 with placebo (p<0.0001). Higher proportions of brepocitinib 45mg-treated participants also achieved CSA-IGA “Clear”/“Almost Clear” with ≥2-grade improvement (69% vs 0%; p=0.0047) and functional skin remission (62% vs 0%; p=0.0147) by Week 16. Similar improvements in patient-reported outcomes supported clinical benefit. Brepocitinib 15mg was also associated with clinical improvements, and dose response was observed. Brepocitinib was generally well-tolerated, with a safety profile consistent with approved JAK inhibitors; no serious adverse events were reported.
Conclusions: BEACON represents the first positive, randomized, placebo-controlled trial of a targeted oral therapeutic in CS. Brepocitinib 45mg achieved rapid, significant, and clinically meaningful improvements in skin disease activity and QOL with a potentially favorable benefit:risk profile.