Crinetics Reports Positive Phase 2 Results for Atumelnant in CAH

Crinetics Pharmaceuticals, Inc. has shared promising results from a Phase 2 clinical study of atumelnant, a novel oral adrenocorticotropic hormone (ACTH) receptor antagonist aimed at treating congenital adrenal hyperplasia (CAH) and ACTH-dependent Cushing’s syndrome. This investigational drug, designed for once-daily use, showed significant positive effects on key biomarkers and clinical symptoms associated with CAH.

The Phase 2 TouCAHn trial was an open-label study conducted globally to assess the efficacy, safety, and pharmacokinetics of atumelnant over a 12-week treatment period. It enrolled 28 patients diagnosed with classic CAH due to a deficiency in 21-hydroxylase and who were on stable glucocorticoid replacement therapy. The study primarily measured changes from baseline in morning serum androstenedione (A4) levels and the occurrence of treatment-emergent adverse events. Changes in morning serum 17-hydroxyprogesterone (17-OHP) were also examined as secondary endpoints.

The trial results revealed that atumelnant administration led to rapid, substantial, and statistically significant reductions in A4 levels, an essential biomarker for managing CAH. Across all administered doses, the reduction in A4 was both substantial and sustained throughout the 12-week period. Additionally, meaningful decreases in 17-OHP levels, another key biomarker for CAH disease control, were achieved across the different dosage groups.

In terms of clinical outcomes, atumelnant positively impacted multiple clinical signs and symptoms of CAH. Notable improvements included a significant reduction and normalization of testosterone levels in the majority of female participants, with some resuming menstruation. There was also a consistent reduction in total adrenal volume and resolution of androgen-mediated polycythemia among several participants.

Atumelnant proved to be generally well-tolerated, with no severe or serious treatment-related adverse events reported. Participants did not require any dose adjustments, and none withdrew from the trial due to adverse effects. Most adverse events were mild to moderate and transient, with the most common being headaches and fatigue.

The success of the Phase 2 trial supports the initiation of a Phase 3 clinical trial to further evaluate atumelnant's potential in treating adults with CAH. Crinetics Pharmaceuticals is also preparing to commence a Phase 2b/3 trial targeted at pediatric patients with CAH later this year. This progress aligns with the company’s strategic vision to enhance its pipeline with innovative therapeutic candidates for endocrine disorders.

Atumelnant represents a significant advancement in addressing diseases linked to excessive ACTH levels, which can substantially affect both physical and mental health. By selectively targeting the melanocortin type 2 receptor on adrenal glands, atumelnant effectively reduces adrenally derived glucocorticoids and androgens regulated by ACTH.

Crinetics Pharmaceuticals continues to focus on the discovery and development of new therapeutics for endocrine diseases. In addition to atumelnant, the company's pipeline includes paltusotine, an investigational drug for acromegaly and carcinoid syndrome associated with neuroendocrine tumors. Crinetics remains committed to advancing its research programs to address various endocrine conditions, including hyperparathyroidism, polycystic kidney disease, and other related disorders.