CRF1 antagonists (crinecerfont, approved by FDA in December 2024), MC2R antagonists (atumelnant, soon phase 3; OMass MC2R antagonist compounds, waiting phase 1), and ACTH-neutralizing monoclonal antibodies (Lu AG13909, ongoing phase 2) have demonstrated the potential to suppress/block ACTH, reduce adrenal androgen excess, and improve disease control while preserving adrenal integrity and enabling more physiologic glucocorticoid dosing. The gene discussed is MC2R; the disease is hyperandrogenism.