VRTX Week: CAH deep dive on atumelnant

Atumelnant could address residual unmet need in CAH. We review the CAH treatment landscape and clinical program for atumelnant, acquired by VRTX through CRNX. The once-daily oral MC2R antagonist blocks ACTH signaling directly at the adrenal gland, offering a distinct approach from NBIX's Crenessity, which acts upstream at the pituitary. CRNX reported encouraging topline phase 2 results in Jan 2025. The adult phase 3 CALM-CAH trial initiated in Dec 2025, and we await further guidance on topline timing. Our recent KOL discussions suggest better androgen control and/or further GC reduction could support a role alongside Crenessity in patients with remaining treatment needs. VRTX remains a top biotech pick with a Buy and $667 PO. The open-label phase 2 TouCAHn study showed mean A4 declines of 58-80% across stable-GC cohorts at week 12, while Cohort 4 (mid-dose with tapering) showed 67% A4 and 49% 17-OHP reductions;