Crinetics Pharmaceuticals Receives FDA Orphan Drug Designation For Atumelnant In The Treatment Of Congenital Adrenal Hyperplasia (CAH)

Crinetics Pharmaceuticals, Inc. has announced that the U.S. Food and Drug Administration (FDA) has granted Orphan Drug Designation (ODD) to atumelnant, the company’s novel once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist being developed for the treatment of classic congenital adrenal hyperplasia (CAH). Atumelnant is the first and only small molecule ACTH receptor antagonist currently in clinical development.

In January 2025, Crinetics reported strong topline results from the Phase 2 TouCAHn trial evaluating atumelnant in adults with classic CAH. The trial showed substantial, rapid, and sustained reductions in key biomarkers across all tested doses, including up to an 80% mean reduction in androstenedione. Clinical improvements were also observed, such as the resumption of menses and reductions in adrenal size, highlighting the therapy’s potential to address both biochemical and clinical aspects of the disease. Based on these results, Crinetics plans to initiate the CALM-CAH Phase 3 study in adults and the BALANCE-CAH Phase 2/3 study in pediatric patients in the second half of 2025.

Dana Pizzuti, M.D., Chief Medical and Development Officer of Crinetics, stated, “Receiving Orphan Drug Designation from the FDA underscores the significant unmet need faced by people living with CAH. Through Atumelnant's innovative mechanism of action, we have developed an ambitious and uncompromising endpoint for our Phase 3 trial, which can demonstrate the ability to restore normal levels of adrenal androgens and reduce glucocorticoid supplementation to physiologic levels. We will also document other changes in clinical disease markers and symptoms that improve quality of life for patients.”

Classic CAH is a rare genetic disorder caused by mutations that impair cortisol synthesis. This disruption leads to persistently elevated ACTH levels, driving the overproduction of androgens such as androstenedione and other steroid precursors. Clinically, this can cause reduced fertility in both men and women, excessive facial hair and acne in women, and painful testicular adrenal rest tumors in men. 

Patients require cortisol replacement therapy, but current treatment typically involves long-term glucocorticoid supplementation at supraphysiologic doses. While effective in replacing cortisol, these high doses can result in serious complications linked to glucocorticoid excess, including weight gain, diabetes, cardiovascular disease, and osteoporosis.

The FDA grants Orphan Drug Designation to therapies intended for the safe and effective treatment, diagnosis, or prevention of rare diseases affecting fewer than 200,000 people in the U.S. Benefits of this designation may include exemptions from certain FDA fees, eligibility for financial incentives to support clinical development, and seven years of market exclusivity in the U.S. upon regulatory approval. With this designation and promising clinical results, Crinetics is advancing atumelnant as a potentially first-in-class treatment for patients with classic CAH, aiming to improve both disease management and long-term patient outcomes.