Crenessity Reduces Glucocorticoid Dosing in CAH

These data will be presented at the 2025 Joint Congress of European Society for Paediatric Endocrinology and the European Society of Endocrinology in Copenhagen, Denmark.

Overproduction of androstenedione, a key adrenal androgen, in pediatric patients with congenital adrenal hyperplasia (CAH) can lead to abnormal growth and development, premature puberty and various developmental challenges. For decades, high levels of androstenedione (A4) were treated with glucocorticoids (GCs) only.

"High-dose steroids are often accompanied by side effects and complications," said Eiry W. Roberts, M.D., Chief Medical Officer, Neurocrine Biosciences. "By enabling patients to maintain or improve their androgen levels while reducing their reliance on high-dose glucocorticoids, Crenessity has the potential to meaningfully enhance long-term outcomes, helping patients with both the hormonal imbalances that characterize CAH, as well as the challenges associated with chronic high-dose glucocorticoid treatment."

The CAHtalyst Pediatric study included 103 patients who were randomly assigned to receive either Crenessity (N=69) or a placebo (N=34) for 28 weeks. The primary endpoint was the least-squares (LS) mean change from baseline in A4 levels (before the morning GC dose) at Week 4. A key secondary endpoint was GC dose reduction at Week 28. Prespecified subgroup analyses of the primary endpoint and post-hoc subgroup analyses of GC dose reduction at Week 28 were conducted for region, sex, race, age, body mass index, pubertal stage and baseline A4 levels; and weight and baseline GC dose subgroups were also analyzed for GC dose reduction at Week 28. This comprehensive approach allowed for a thorough evaluation of treatment effects across diverse patient characteristics.

Across all subgroups, Crenessity enabled reduction of GC doses while maintaining or improving A4 levels: i) Substantial Reduction in Adrenal Androgens at Week 4: Crenessity significantly reduced A4 levels from baseline compared with placebo (overall, -6.9 versus +2.5 nmol/L; LS mean difference [LSMD]: -9.3 nmol/L; p=0.0002); subgroup analyses of A4 reduction at Week 4 were consistent with the results in the overall population. ii) Substantial Reduction in GC Doses at Week 28: GC doses were significantly reduced from baseline with Crenessity (while maintaining or improving A4 levels) compared with placebo (overall, -18.0% versus +5.6%; LSMD: -23.5%; p<0.0001); subgroup analyses of GC reduction at Week 28 were consistent with the results in the overall population. Crenessity was generally well tolerated in the CAHtalyst Pediatric study. The most common adverse reactions (≥4% for Crenessity and greater than placebo) were headache, abdominal pain, fatigue, nasal congestion and nosebleed.

The ability to reduce GC doses while simultaneously maintaining or improving androgen levels represents a significant advancement in CAH management. These results suggest that Crenessity may improve long-term outcomes in patients across various subgroups.

About The CAHtalyst  Pediatric Study
The Phase  III CAHtalyst global registrational studies were designed to evaluate the safety, efficacy and tolerability of Crenessity in children and adults with classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency. The CAHtalyst studies were the largest-ever interventional clinical trial program in classic CAH, including 285 pediatric and adult patients. The CAHtalyst Pediatric study included 103 pediatric patients four to 17 years of age. The study tested two questions. The first question evaluated whether four weeks of Crenessity treatment could improve androgen control. The second question evaluated whether an additional 24 weeks of Crenessity treatment could enable customized glucocorticoid (GC) down-titration while androstenedione levels were maintained or improved. Data from the CAHtalyst Phase III studies supported approval of Crenessity by the FDA in December 2024. The open-label extension treatment portions of both studies are ongoing.