Crinetics Pharmaceuticals, Inc. revealed encouraging results from its ongoing clinical trials of atumelnant (CRN04894), a novel, once-daily oral adrenocorticotropic hormone (ACTH) receptor antagonist, at the Endocrine Society’s annual meeting (ENDO2024). The findings come from two studies: the Phase 2 TouCAHn study in participants with congenital adrenal hyperplasia (CAH) and the Phase 1b/2a study in participants with ACTH-dependent Cushing’s syndrome (ADCS).
In the TouCAHn study, participants with classic CAH treated with atumelnant (80 mg) experienced profound, rapid, and sustained reductions in key adrenal steroids, with 100% maintaining androstenedione (A4) levels below the upper limit of normal (ULN) from two weeks through 12 weeks. Significant reductions in 17-hydroxyprogesterone (17-OHP) were also observed, with a 97% reduction at two weeks and 94% at 12 weeks. The study is ongoing, with topline results expected in the second half of 2024.
In the ADCS trial, all participants (n=5) treated with atumelnant (80 mg) achieved normalization of 24-hour urinary free cortisol levels within 10 days, with serum cortisol levels dropping below 5 mcg/dL. Improvements in clinical symptoms were noted in all patients, highlighting atumelnant's potential to address the unmet needs in this patient population.
Atumelnant was well tolerated across both studies, with adverse events being mild to moderate and transient. The most common adverse events included fatigue, headache, and upper respiratory tract infection in the CAH study, and headache, nausea, and decreased appetite in the ADCS study. No severe or serious treatment-emergent adverse events were reported, and no participants discontinued from the trials.
These findings underscore the potential of atumelnant as a groundbreaking treatment for CAH and ADCS, offering a novel mechanism of action by directly inhibiting ACTH at its receptor. Crinetics Pharmaceuticals continues to advance its clinical development program, with further results anticipated in the coming months.
