Brepocitinib BEACON Phase 2: Topline Efficacy and Safety in Cutaneous Sarcoidosis

BEACON Phase 2 evaluated brepocitinib in cutaneous sarcoidosis and found a rapid improvement signal in lesion activity that is informing pivotal planning. By Week 16, mean CSAMI-A change from baseline was −22.3 with brepocitinib 45 mg versus −0.7 with placebo (between-group difference 21.6 points; P<0.0001) in a small randomized cohort (N=31), yielding clear statistical separation with estimates still limited by sample size. The Week 16 readout supports Phase 3 planning in cutaneous sarcoidosis, while durability of response and uncommon safety events remain outside what this short trial can define.

Trial design matters for interpreting the Week 16 CSAMI-A signal. BEACON Phase 2 enrolled 31 patients across 15 US sites and randomized participants 3:2:2 to once-daily brepocitinib 45 mg (n=13), brepocitinib 15 mg (n=11), or placebo (n=7) for a 16-week treatment period. CSAMI-A is an activity-focused clinician assessment for cutaneous sarcoidosis, capturing inflammatory lesion activity rather than mechanism. Week 16 is also a practical planning horizon for registrational development, pairing a feasible controlled-treatment window with an interpretable skin activity endpoint.

The efficacy separation at Week 16 was large in absolute terms and appeared early for the higher dose. In BEACON Phase 2 results, mean CSAMI-A change at Week 16 was −22.3 for brepocitinib 45 mg compared with −0.7 for placebo (Δ21.6; P<0.0001), with separation reported as early as Week 4 and maintained through Week 16. Placebo change remained small, so the between-group difference largely reflected improvement on active therapy. For dose selection, the topline findings position 45 mg as the clearest signal-bearing dose for a pivotal program anchored to Week 16 skin activity change.

Responder thresholds on CSAMI-A aligned with the mean change and added a clinically intuitive view of treatment effect. At Week 16, 100% of patients receiving brepocitinib 45 mg achieved a ≥10-point CSAMI-A improvement versus 14% on placebo (P=0.0002), and 62% reached CSAMI-A <5 (“functional remission”) versus 0% on placebo (P=0.0147). Other clinician- and patient-facing measures moved in the same direction: 69% of the 45 mg arm achieved a two-step Investigator’s Global Assessment improvement to Clear/Almost Clear versus 0% on placebo (P=0.0047), and 100% of the 45 mg arm reported improvement on the Patient’s Global Impression of Change versus 29% on placebo (P=0.0014); skin-related quality-of-life instruments (KSQ Skin Domain and Skindex-16) were also reported to favor 45 mg. The convergence across clinician-rated activity, patient-perceived change, and skin QoL supports a pattern consistent with patient-relevant benefit, with confirmation still needed in larger cohorts to tighten effect-size estimates.

Safety reporting over 16 weeks was described as favorable, though the available information is best viewed as an initial topline snapshot rather than a fully characterizable profile. No serious adverse events were reported in the brepocitinib 45 mg arm, and adverse events during the study period were described as mild or moderate. The summary does not include granular treatment-emergent adverse event tables, discontinuation counts, or laboratory abnormality detail, which limits cross-arm comparisons and assessment of dose-related tolerability beyond broad severity categories. In that context, short-term tolerability appears encouraging at Week 16 while remaining incompletely defined on the basis of topline results alone.

Pivotal planning now turns on whether the Week 16 CSAMI-A signal and responder profile can be translated into a package with adequate duration, endpoint hierarchy, and prospective safety monitoring. The sponsor described an intent to initiate a pivotal Phase 3 program in cutaneous sarcoidosis in calendar 2026 following FDA engagement, and separately noted New Drug Application activity for brepocitinib in dermatomyositis as context for cross-indication development. These timelines are forward-looking, but they clarify the next decision points: how CSAMI-A will be positioned relative to global and patient-reported measures, how long controlled treatment will extend beyond Week 16, and how safety reporting will be expanded with transparent discontinuation accounting and prespecified monitoring parameters.