Crinetics Pharmaceuticals, Inc. announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to atumelnant, its once-daily oral ACTH receptor antagonist candidate for treating classic congenital adrenal hyperplasia (CAH). Atumelnant is the first and only small molecule ACTH receptor antagonist currently in clinical development.
CAH is a rare genetic disorder caused by impaired cortisol synthesis, leading to excess production of adrenal androgens and steroid precursors, which cause a range of severe symptoms including fertility issues, excessive facial hair, acne, and adrenal tumors. Current treatments rely on chronic glucocorticoid supplementation, often at high doses, which can cause serious side effects such as weight gain, diabetes, and cardiovascular problems.
“Atumelnant’s novel mechanism targets a critical driver of CAH symptoms, and the FDA’s Orphan Drug Designation highlights the urgent unmet medical need in this patient population,” said Dana Pizzuti, M.D., Chief Medical and Development Officer of Crinetics. “Our Phase 3 trial aims to show atumelnant’s ability to restore normal adrenal androgen levels while reducing glucocorticoid use, improving quality of life for patients.”
The designation follows robust Phase 2 TouCAHn trial results reported in January 2025, demonstrating up to an 80% reduction in androstenedione levels and improvements in clinical symptoms such as menstrual resumption and reduced adrenal size. Crinetics plans to initiate Phase 3 CALM-CAH adult and Phase 2/3 BALANCE-CAH pediatric trials in the second half of 2025.
The FDA grants Orphan Drug Designation to therapies addressing rare diseases affecting fewer than 200,000 people in the U.S., offering benefits such as fee exemptions, development incentives, and seven years of market exclusivity upon approval.