The VALOR study demonstrated a mean TIS improvement of 46.5 with brepocitinib 30 mg versus 31.2 for placebo (p=0.0006) at week 52. How clinically meaningful is this 15-point differential, and what does it reveal about brepocitinib’s overall impact on disease activity across domains?

This was the first-ever 52-week placebo-controlled study to achieve a positive outcome in dermatomyositis. Why is the duration and robustness of this trial critical in validating efficacy and durability of benefit for a chronic autoimmune condition like DM?

Brepocitinib achieved statistically significant improvements across all nine key secondary endpoints, including CDASI and MMT-8. How important is this breadth of benefit across both cutaneous and muscular components in establishing comprehensive disease control?

Over 60% of patients on brepocitinib 30 mg reduced corticosteroid doses to ≤2.5 mg/day, and 42% discontinued steroids entirely. How do these results shape the conversation around steroid-sparing strategies and long-term toxicity management in DM?

Significant separation from placebo was observed as early as week 4, with median time to moderate response (TIS≥40) at eight weeks. What does this rapid onset suggest about the drug’s mechanism of action and potential to improve early quality of life outcomes?

A clear dose-response was observed, establishing 30 mg as the optimal dose. How do you interpret this differentiation, and how might it inform individualized dosing strategies or future label considerations?

The safety profile was consistent with prior brepocitinib studies, with no excess in malignancy, cardiovascular, or thromboembolic events. How reassuring are these data for long-term use, given the safety concerns often associated with JAK and TYK2 pathway inhibitors?

With NDA submission planned for the first half of 2026, what are the key regulatory and clinical milestones ahead, and how could brepocitinib reshape the current treatment paradigm for dermatomyositis, where no targeted therapies are yet approved?