New data support crinecerfont for pediatric congenital adrenal hyperplasia

New data support crinecerfont for pediatric congenital adrenal hyperplasia | Image Credit: © Osada - stock.adobe.com.

On May 8, 2025, Neurocrine Biosciences announced new results from subgroup analyses of its phase 3 CAHtalyst pediatric study evaluating crinecerfont (CRENESSITY; Neurocrine Biosciences) in children with classic congenital adrenal hyperplasia (CAH).¹

CAH is a rare genetic disorder caused by an enzyme deficiency that impairs the body’s ability to produce key adrenal steroid hormones, including cortisol and aldosterone. In about 95% of cases, this condition results from mutations in the CYP21A2 gene, leading to a deficiency of the enzyme 21-hydroxylase. ²

When this enzyme is lacking, the body cannot make enough cortisol, and often aldosterone, which can result in salt wasting, dehydration, and other life-threatening complications. At the same time, the body continues to produce adrenal androgens, including androstenedione, at elevated levels. This overproduction can lead to early or abnormal growth, premature puberty, and developmental challenges.²

Findings from the study showed that pediatric patients who received crinecerfont could maintain or improve their androstenedione (A4) levels while reducing their glucocorticoid (GC) doses, according to the company. These findings were consistent across all of the patient subgroups analyzed.

Historically, treatment has focused on managing high A4 levels through the use of high-dose glucocorticoids. While this approach can control hormone levels, it also increases the risk of steroid-related side effects. “High-dose steroids are often accompanied by side effects and complications,” said Eiry W. Roberts, MD, chief medical officer of 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 enrolled 103 children with classic CAH. Participants were randomized to receive either crinecerfont (n = 69) or a placebo (n = 34) for a duration of 28 weeks. The primary outcome measured was the least-squares mean change in A4 levels from baseline at week 4, taken before the morning glucocorticoid dose. A key secondary endpoint was the change in GC dosing at week 28.

To better understand how treatment affected different types of patients, subgroup analyses were conducted. These included prespecified subgroups based on region, sex, race, age, body mass index, pubertal stage, and baseline A4 levels. Post-hoc subgroup analyses also examined weight and baseline GC dose in relation to the week 28 GC reduction endpoint.

Across all subgroups, patients treated with crinecerfont saw reductions in A4 and GC dosing:

• Androgen levels: At week 4, the average A4 level in the crinecerfont group decreased by 6.9 nmol/L from baseline, compared with an increase of 2.5 nmol/L in the placebo group. The least-squares mean difference between the groups was -9.3 nmol/L (P = 0.0002). Subgroup analyses showed results consistent with the overall population.
• Glucocorticoid reduction: By week 28, children receiving crinecerfont experienced an average GC dose reduction of 18.0%, compared with a 5.6% increase in the placebo group. The least-squares mean difference was -23.5% (P < 0.0001), with consistent effects observed across all subgroups.

Crinecerfont was generally well tolerated. The most frequently reported adverse reactions (occurring in at least 4% of patients and more often than in the placebo group) included headache, abdominal pain, fatigue, nasal congestion, and nosebleed.

The results of the full study will be presented at the 2025 Joint Congress of the European Society for Paediatric Endocrinology and the European Society of Endocrinology, taking place in Copenhagen, Denmark, according to the company.

Neurocrine Biosciences will also present additional findings at the Joint Congress, including 1-year results from the CAHtalyst Adult study and data from the CHAMPAIN study comparing modified-release hydrocortisones in adrenal insufficiency.

References:

1. Neurocrine Biosciences. Neurocrine Biosciences Announces New Results from Exploratory Analyses of the Phase 3 CAHtalyst™ Pediatric Study Demonstrating CRENESSITY™ Reduces Glucocorticoid Dosing While Maintaining or Improving Androstenedione Across Patient Subgroups. PR Newswire. May 8, 2025. Accessed May 9, 2025. https://www.prnewswire.com/news-releases/neurocrine-biosciences-announces-new-results-from-exploratory-analyses-of-the-phase-3-cahtalyst-pediatric-study-demonstrating-crenessity-reduces-glucocorticoid-dosing-while-maintaining-or-improving-androstenedione-across-patient-302449317.html

2. Sarafoglou K, Kim MS, Lodish M, et al. Phase 3 Trial of Crinecerfont in Pediatric Congenital Adrenal Hyperplasia. N Engl J Med. 2024;391(6):493-503. doi:10.1056/NEJMoa2404655