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

“Receiving Orphan Drug Designation from the FDA underscores the significant unmet need faced by people living with CAH,” said Dana Pizzuti, M.D., Chief Medical and Development Officer of Crinetics. “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.”

In January 2025, Crinetics reported robust positive topline results from the Phase 2 TouCAHn trial of atumelnant in adults with classic CAH. The study demonstrated substantial, rapid and sustained reductions of key biomarkers across doses, including up to an 80% mean reduction in androstenedione. The study also demonstrated meaningful improvements in multiple clinical signs and symptoms of the disease affecting patient health, including resumption of menses and reduction of adrenal size. Crinetics expects the first participants randomized in the CALM-CAH Phase 3 study in adults and the BALANCE-CAH Phase 2/3 study in pediatrics in the second half of 2025.

CAH is caused by genetic mutations that result in impaired cortisol synthesis. This lack of cortisol leads to a breakdown of feedback mechanisms and results in persistently high levels of ACTH that in turn results in the over secretion of steroids, particularly androgens like androstenedione, and steroid precursors. High levels of androgens can manifest as reduced fertility in men and women, excessive facial hair and acne in women, and painful testicular adrenal rest tumors in men. Patients also need cortisol supplementation to replace the missing cortisol. However, the current treatment paradigm involves chronic glucocorticoid steroid supplementation, often at supraphysiologic levels, which can lead to significant additional medical problems associated with glucocorticoid excess including weight gain, diabetes, cardiovascular issues, and osteoporosis.  

The FDA provides ODD status to drugs intended for the safe and effective treatment, diagnosis, or prevention of rare diseases that affect fewer than 200,000 people in the U.S. Benefits of the designation may include exemption from certain FDA fees, financial incentives for qualified clinical development, and seven years of market exclusivity in the U.S. if the treatment is approved.

Source: globenewswire.com