Neurocrine Biosciences, Inc. announced that it will present CAHtalyst Adult Phase 3 clinical study baseline characteristics for adults with congenital adrenal hyperplasia (CAH) enrolled in the study, as well as data from a comprehensive literature review assessing the impact of supraphysiologic glucocorticoid (GC) doses on psychiatric disorders and cognition in patients with CAH. The CAHtalyst Adult study baseline data demonstrate the potential long-term consequences of current CAH treatments, with many patients in young adulthood experiencing disorders found more commonly in people decades older, including osteopenia, hypertension and hyperlipidemia. In addition, the results of a comprehensive literature review showed that many CAH patients receiving supraphysiologic GC doses had an increased risk of psychiatric and cognitive symptoms. These new data were presented at oral presentations and poster sessions at the American Association of Clinical Endocrinology 2024 Annual Meeting in New Orleans.

CAHtalyst Phase 3 Adult Study Baseline Characteristics: Baseline characteristics of 182 adults with CAH enrolled in the CAHtalyst Adult Phase 3 study were summarized in an oral presentation at the conference by Oksana Hamidi, M.D., Associate Professor in the Division of Endocrinology and Metabolism at UT Southwestern Medical Center. Despite supraphysiologic GC dosing, levels of adrenocorticotropic hormone, 17-hydroxyprogesterone and androstenedione (A4) were elevated at baseline, with levels of testosterone (females) and A4/testosterone (males) also elevated. Common comorbidities included anxiety, osteopenia, depression, hypertension and hyperlipidemia.

Overall, close to half of participants were overweight. Forty-seven percent of females reported a history of hirsutism (excessive hair growth) and acne (23%), and testicular adrenal rest tumors were identified in 66% of male participants. In 2023, Neurocrine Biosciences announced top-line data from the CAHtalyst Pediatric and CAHtalyst Adult Phase 3 clinical studies evaluating the efficacy, safety, and tolerability of crinecerfont in children, adolescents, and adults with CAH due to 21-hydroxylase deficiency.

The data from both studies supported two New Drug Applications submitted to the U.S. Food and Drug Administration in April 2024. Literature Review: Psychological and Cognitive Impact of Supraphysiologic Glucocorticoids: Neurocrine Biosciences also presented the results of a comprehensive review of available literature between 1996?2023 focusing on the use of supraphysiologic doses of hydrocortisone and their effect on psychiatric disorders and cognition in patients with CAH (Poster# 05). The review identified mood and psychotic disorders as the most consistent psychiatric disorders seen.

Brain morphology in patients with CAH was altered (white matter microstructure abnormalities), suggesting an increased risk of cognitive impairment with use of supraphysiologic doses of GCs in these patients.