Crinecerfont, an investigational oral treatment, has shown promising results in a phase 3 study for treating children and adolescents with classic congenital adrenal hyperplasia (CAH). The study involved 103 participants aged 2 to 17 and demonstrated that crinecerfont significantly reduced serum androstenedione levels compared to placebo. This reduction was observed following a glucocorticoid (GC) stable period, with a statistically significant decrease from baseline at week 4 (P = .0002).
Patients treated with crinecerfont were able to decrease their daily GC dose while maintaining androgen control, a significant achievement in CAH management. Approximately 30% of crinecerfont-treated patients achieved a reduction to a physiologic GC dose while keeping androgen control, compared to 0% in placebo-treated patients. Additionally, a statistically significant decrease in serum 17-hydroxyprogesterone from baseline at week 4 was observed compared to placebo (P < .0001).
The phase 3 pediatric study, which began in July 2021, was a 28-week, randomized, double-blind, placebo-controlled study. It evaluated the efficacy, safety, and tolerability of crinecerfont in children and adolescents with CAH due to 21-hydroxylase deficiency. The study's findings suggest that crinecerfont could shift the treatment paradigm for CAH, offering a potential solution for managing the condition without relying on traditional glucocorticoid treatments.
Currently, there are no nonglucocorticoid treatments approved by the FDA for classic CAH. Traditional GC treatment at supraphysiologic doses has been associated with complications such as weight gain, diabetes, cardiovascular disease, and osteoporosis. Long-term treatment with supraphysiologic GC doses could also lead to cognitive and psychological impacts, abnormal bone growth and development in pediatric patients, female health problems, testicular rest tumors in males, and fertility issues in both sexes.
The positive phase 3 data for crinecerfont represents a significant step forward in the treatment of CAH, potentially improving clinical outcomes related to androgen excess and chronic supraphysiologic glucocorticoid dosing. The ongoing open-label crinecerfont treatment and optional open-label extension portion of the study will provide further insights into the long-term efficacy and safety of this innovative treatment approach.
